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Find video protocols related to scientific articles indexed in Pubmed.
Breast cancer susceptibility variants and mammographic density phenotypes in norwegian postmenopausal women.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 07-07-2014
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Mammographic density (MD) is one of the strongest known breast cancer risk factors. Twin studies have suggested that a large part of the variation in MD is genetically determined. We hypothesized that breast cancer susceptibility variants may affect MD, and that their effects may be modified by nongenetic factors.
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Results of delayed triage by HPV testing and cytology in the Norwegian Cervical Cancer Screening Programme.
Acta Oncol
PUBLISHED: 06-25-2014
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Background. High-risk human papilloma virus (hrHPV) testing was added to the cytology triage of women with equivocal screening smears in the Norwegian programme for cervical cancer screening in 2005. In this population-based observational before and after study we assessed the effect of changing the screening algorithm. Material and methods. In periods before and after the change 75 852 and 66 616 women, respectively, were eligible for triage, i.e. they had smear results of unsatisfactory, atypical squamous cells of undetermined significance (ASC-US), or low-grade squamous intraepithelial lesion (LSIL) at routine screening. The triage was delayed as supplementary testing started six months after the initial screening. The groups were compared with respect to results of triage and later three-year cumulative incidence of cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Results. Before and after the change in the screening algorithm 5.2% (3964/75 852) and 8.1% (5417/66 616) of women, respectively, were referred to colposcopy. Among women referred to colposcopy cumulative incidence of CIN2+ (positive predictive value of referral) increased from 42.0% [95% confidence interval (CI): 40.3 - 43.7%] in the period with cytology only to 48.0% (95% CI 46.6 - 49.4%) after the start of HPV testing. For women recalled to ordinary screening the three-year cumulative incidence decreased from 2.7% (95% CI 2.5 - 2.9%) to 1.0% (95% CI 0.9 - 1.2%) during the same period. Among women with LSIL at routine screening and HPV testing in triage, 52.5% (1976/3766) were HPV positive. Conclusion. The new algorithm with HPV testing implemented in 2005 resulted in an increased rate of referral to colposcopy, but in a better risk stratification with respect to precancerous disease.
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Cross-cancer pleiotropic analysis of endometrial cancer: PAGE and E2C2 consortia.
Carcinogenesis
PUBLISHED: 05-15-2014
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Genome-wide association studies (GWAS) have identified a large number of cancer-associated single nucleotide polymorphisms (SNPs), several of which have been associated with multiple cancer sites suggesting pleiotropic effects and shared biological mechanisms across some cancers. We hypothesized that SNPs associated with other cancers may be additionally associated with endometrial cancer. We examined 213 SNPs previously associated with 14 other cancers for their associations with endometrial cancer in 3758 endometrial cancer cases and 5966 controls of European ancestry from two consortia: Population Architecture Using Genomics and Epidemiology and the Epidemiology of Endometrial Cancer Consortium. Study-specific logistic regression estimates adjusted for age, body mass index and the most significant principal components of genetic ancestry were combined using fixed-effect meta-analysis to evaluate the association between each SNP and endometrial cancer risk. A Bonferroni-corrected P value of 2.35×10(-4) was used to determine statistical significance of the associations. SNP rs7679673, ~6.3kb upstream of TET2 and previously reported to be associated with prostate cancer risk, was associated with endometrial cancer risk in the direction opposite to that for prostate cancer [meta-analysis odds ratio = 0.87 (per copy of the C allele), 95% confidence interval = 0.81, 0.93; P = 7.37×10(-5)] with no evidence of heterogeneity across studies (P heterogeneity = 0.66). This pleiotropic analysis is the first to suggest TET2 as a susceptibility locus for endometrial cancer.
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Mammographic density phenotypes and risk of breast cancer: a meta-analysis.
J. Natl. Cancer Inst.
PUBLISHED: 05-10-2014
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Fibroglandular breast tissue appears dense on mammogram, whereas fat appears nondense. It is unclear whether absolute or percentage dense area more strongly predicts breast cancer risk and whether absolute nondense area is independently associated with risk.
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Insulin-like growth factor-1, growth hormone, and daily cycling estrogen are associated with mammographic density in premenopausal women.
Cancer Causes Control
PUBLISHED: 04-17-2014
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Mammographic density represents epithelial and stromal proliferation, while insulin-like growth factor (IGF)-1, insulin-like growth factor-binding protein-3, growth hormone (GH), and estrogen may influence cellular proliferation. However, whether these growth factors independently, or in combination with estrogen, influence mammographic density in premenopausal women remains unclear.
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A genome-wide association study of early-onset breast cancer identifies PFKM as a novel breast cancer gene and supports a common genetic spectrum for breast cancer at any age.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 02-03-2014
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Early-onset breast cancer (EOBC) causes substantial loss of life and productivity, creating a major burden among women worldwide. We analyzed 1,265,548 Hapmap3 single-nucleotide polymorphisms (SNP) among a discovery set of 3,523 EOBC incident cases and 2,702 population control women ages ? 51 years. The SNPs with smallest P values were examined in a replication set of 3,470 EOBC cases and 5,475 control women. We also tested EOBC association with 19,684 genes by annotating each gene with putative functional SNPs, and then combining their P values to obtain a gene-based P value. We examined the gene with smallest P value for replication in 1,145 breast cancer cases and 1,142 control women. The combined discovery and replication sets identified 72 new SNPs associated with EOBC (P < 4 × 10(-8)) located in six genomic regions previously reported to contain SNPs associated largely with later-onset breast cancer (LOBC). SNP rs2229882 and 10 other SNPs on chromosome 5q11.2 remained associated (P < 6 × 10(-4)) after adjustment for the strongest published SNPs in the region. Thirty-two of the 82 currently known LOBC SNPs were associated with EOBC (P < 0.05). Low power is likely responsible for the remaining 50 unassociated known LOBC SNPs. The gene-based analysis identified an association between breast cancer and the phosphofructokinase-muscle (PFKM) gene on chromosome 12q13.11 that met the genome-wide gene-based threshold of 2.5 × 10(-6). In conclusion, EOBC and LOBC seem to have similar genetic etiologies; the 5q11.2 region may contain multiple distinct breast cancer loci; and the PFKM gene region is worthy of further investigation. These findings should enhance our understanding of the etiology of breast cancer.
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Food items contributing most to variation in antioxidant intake; a cross-sectional study among Norwegian women.
BMC Public Health
PUBLISHED: 01-12-2014
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Fruit and vegetable intake has been found to reduce the risk of cardiovascular disease, certain types of cancer and diabetes mellitus. It is possible that antioxidants play a large part in this protective effect. However, which foods account for the variation in antioxidant intake in a population is not very clear. We used food frequency data from a population-based sample of women to identify the food items that contributed most to the variation in antioxidant intake in Norwegian diet.
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Methods for assessing and representing mammographic density: an analysis of 4 case-control studies.
Am. J. Epidemiol.
PUBLISHED: 10-11-2013
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To maximize statistical power in studies of mammographic density and breast cancer, it is advantageous to combine data from several studies, but standardization of the density assessment is desirable. Using data from 4 case-control studies, we describe the process of reassessment and the resulting correlation between values, identify predictors of differences in density readings, and evaluate the strength of the association between mammographic density and breast cancer risk using different representations of density values. The pooled analysis included 1,699 cases and 2,422 controls from California (1990-1998), Hawaii (1996-2003), Minnesota (1992-2001), and Japan (1999-2003). In 2010, a single reader reassessed all images for mammographic density using Cumulus software (Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada). The mean difference between original and reassessed percent density values was -0.7% (95% confidence interval: -1.1, -0.3), with a correlation of 0.82 that varied by location (r = 0.80-0.89). Case status, weight status, age, parity, density assessment method, mammogram view, and race/ethnicity were significant determinants of the difference between original and reassessed values; in combination, these factors explained 9.2% of the variation. The associations of mammographic density with breast cancer and the model fits were similar using the original values and the reassessed values but were slightly strengthened when a calibrated value based on 100 reassessed radiographs was used.
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Dietary patterns and breast cancer risk in the California Teachers Study cohort.
Am. J. Clin. Nutr.
PUBLISHED: 10-09-2013
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Evidence that diet is associated with breast cancer risk is inconsistent. Most studies have examined risks associated with specific foods and nutrients, rather than measures of overall diet.
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Urinary estrogen metabolites and breast cancer: a combined analysis of individual level data.
Int. J. Biol. Markers
PUBLISHED: 09-13-2013
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Circulating estrogens are associated with increased breast cancer risk, yet the role of estrogen metabolites in breast carcinogenesis remains unclear. This combined analysis of 5 published studies evaluates urinary 2-hydroxyestrone (2-OHE1), 16?-hydroxyestrone (16?-OHE1), and their ratio (2:16?-OHE1) in relation to breast cancer risk.
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Reproductive factors, exogenous hormones, and pancreatic cancer risk in the CTS.
Am. J. Epidemiol.
PUBLISHED: 09-05-2013
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Female steroid hormones are hypothesized to play a protective role in pancreatic cancer risk. However, results from epidemiologic studies that examined hormone-related exposures have been inconsistent. The California Teachers Study is a cohort study of female public school professionals that was established in 1995-1996. Of the 118,164 eligible study participants, 323 women were diagnosed with incident invasive pancreatic cancer through December 31, 2009. Multivariable Cox proportional hazards regression methods were used to estimate hazard ratios and 95% confidence intervals for the association of pancreatic cancer risk with reproductive factors and exogenous hormone use. Current users of estrogen-only therapy at baseline (1995-1996) had a lower risk of pancreatic cancer than did participants who had never used hormone therapy (hazard ratio = 0.59, 95% confidence interval: 0.42, 0.84). Use of estrogen-plus-progestin therapy was not associated with the risk of pancreatic cancer. A longer duration of oral contraceptive use (?10 years of use compared with never use) was associated with an increased risk of cancer (hazard ratio = 1.72, 95% confidence interval: 1.19, 2.49). Reproductive factors, including age at menarche, parity, breastfeeding, and age at menopause, were not associated with pancreatic cancer risk. Our results suggest that increased estrogen exposure through estrogen-only therapy may reduce pancreatic cancer risk in women.
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[Breast cancer surgery in Norway 1986-2009].
Tidsskr. Nor. Laegeforen.
PUBLISHED: 08-24-2013
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Studies have revealed variations in breast cancer survival between different counties in Norway. This study describes trends in surgical treatment of ductal carcinoma in situ (DCIS) and breast cancer in Norway, over time and by county.
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Mammographic breast density response to aromatase inhibition.
Clin. Cancer Res.
PUBLISHED: 03-06-2013
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Mammographic breast density (MBD) is decreased by tamoxifen, but the effect of aromatase inhibitors is less clear.
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Hormone metabolism genes and mammographic density in Singapore Chinese women.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 02-21-2013
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Female steroid hormone levels and exogenous hormone use influence breast cancer risk. We investigated the association between genetic variation in the hormone metabolism and signaling pathway and mammographic density, a strong predictor of breast cancer risk.
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Mediterranean dietary pattern and risk of breast cancer.
PLoS ONE
PUBLISHED: 02-04-2013
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A Mediterranean diet has a recognized beneficial effect on health and longevity, with a protective influence on several cancers. However, its association with breast cancer risk remains unclear.
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Breast cancer mortality in participants of the Norwegian Breast Cancer Screening Program.
Cancer
PUBLISHED: 01-29-2013
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The Norwegian Breast Cancer Screening Program started in 1996. To the authors knowledge, this is the first report using individual-based data on invitation and participation to analyze breast cancer mortality among screened and nonscreened women in the program.
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Genetic variation in transforming growth factor beta 1 and mammographic density in Singapore Chinese women.
Cancer Res.
PUBLISHED: 01-18-2013
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TGF-? plays a critical role in normal mammary development and morphogenesis. Decreased TGF-? signaling has been associated with increased mammographic density. Percent mammographic density (PMD) adjusted for age and body mass index (BMI) is a strong risk factor and predictor of breast cancer risk. PMD is highly heritable, but few genetic determinants have been identified. We investigated the association between genetic variation in TGFB1 and PMD using a cross-sectional study of 2,038 women who were members of the population-based Singapore Chinese Health Study cohort. We assessed PMD using a computer-assisted method. We used linear regression to examine the association between nine tagging single-nucleotide polymorphisms (SNP) of TGFB1 and PMD and their interaction with parity, adjusting for age, BMI, and dialect group. We calculated P values adjusted for correlated tests (P(ACT)) to account for multiple testing. The strongest association was observed for rs2241716. Adjusted PMD was higher by 1.5% per minor allele (P(ACT) = 0.04). When stratifying by parity, this association was limited to nulliparous women. For nulliparous women, adjusted PMD was higher by 8.6% per minor allele (P(ACT) = 0.003; P for interaction with parity = 0.002). Three additional TGFB1 tagging SNPs, which were in linkage disequilibrium with rs2241716, were statistically significantly associated with adjusted PMD (P(ACT) < 0.05) for nulliparous women. However, none of these three SNPs showed statistically significant association after adjusting for rs2241716. Our data support that TGFB1 genetic variation may be an important genetic determinant of mammographic density measure that predicts breast cancer risk, particularly in nulliparous women.
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Variation in inflammatory cytokine/growth-factor genes and mammographic density in premenopausal women aged 50-55.
PLoS ONE
PUBLISHED: 01-01-2013
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Mammographic density (MD) has been found to be an independent risk factor for breast cancer. Although data from twin studies suggest that MD has a strong genetic component, the exact genes involved remain to be identified. Alterations in stromal composition and the number of epithelial cells are the most predominant histopathological determinants of mammographic density. Interactions between the breast stroma and epithelium are critically important in the maturation and development of the mammary gland and the cross-talk between these cells are mediated by paracrine growth factors and cytokines. The potential impact of genetic variation in growth factors and cytokines on MD is largely unknown.
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Characteristics of triple-negative breast cancer in patients with a BRCA1 mutation: results from a population-based study of young women.
J. Clin. Oncol.
PUBLISHED: 10-17-2011
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Triple-negative breast cancers (TNBCs) are tumors with low or no expression of estrogen receptor, progesterone receptor, or human epidermal growth factor receptor 2. These tumors have a poor prognosis, remain a clinical challenge, and are more common among women with BRCA1 mutations. We tested whether there are distinguishing features of TNBC after BRCA1 mutation status has been taken into account.
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Alcohol intake and mammographic density in postmenopausal Norwegian women.
Breast Cancer Res. Treat.
PUBLISHED: 09-27-2011
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Mammographic density is a strong risk factor for breast cancer. While alcohol intake has been associated with increased breast cancer risk, the association between alcohol consumption and mammographic density is not clear. We assessed the association between alcohol consumption and mammographic density among women who participated in the Norwegian Breast Cancer Screening Program in 2004. Mammographic density was assessed on digitized mammograms from 2,251 postmenopausal women aged 50-69 years, using a computer assisted method. Current intake of beer, wine (red and white), and liquor was assessed using a validated food frequency questionnaire. Non-drinkers were defined as complete abstainers (i.e., those who reported no intake of any type of alcohol). We used multivariate linear regression models to estimate least square means of percent mammographic density by categories of alcohol intake with adjustment for potential confounders. We also checked for possible effect modification by stratifying the analyses by age, body mass index, and hormone therapy. The mean percent mammographic density was almost similar for drinkers 18.3% (95% CI: 17.6-18.9%) and non-drinkers 17.8% (95% CI: 16.1-19.4%) (P = 0.59). There was no indication that amount of alcohol consumed was associated with percent mammographic density, with a mean percent density among women with the highest intake (>90 g of alcohol per week) of 18.2% (95% CI: 16.9-19.0%), only slightly different from that of non-drinkers 18.3% (17.3-19.6%) (P for trend = 0.99). There was no association between any type of alcohol consumed and mammographic density.There was no effect modification by body mass index, age, or hormone therapy use. We found no evidence of an association between alcohol intake and percent mammographic density.
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Mammographic density and intake of selected nutrients and vitamins in Norwegian women.
Nutr Cancer
PUBLISHED: 09-14-2011
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Investigating the association between dietary factors and mammographic density (MD) could shed light on the relationship between diet and breast cancer risk. We took advantage of a national mammographic screening program to study the association between intake of nutrients and MD. In this study, we analyzed data of 2,252 postmenopausal women aged 50-69 yr who participated in the Norwegian Breast Cancer Screening Program in 2004. MD was assessed on digitized mammograms using a computer-assisted method. We used multivariate linear regression models to determine least square means of percent and absolute MD. Overall, we observed no associations between MD and intake of total calories, protein, carbohydrates, cholesterol, and dietary fiber. There was a positive borderline statistically significant association between absolute MD and total fat intake (P = 0.10) and between percent MD and intake of saturated fat (P = 0.06). There was no association between MD and intake of calcium, retinol, vitamins A, B12, C, or D, or combined intake of vitamin D and calcium. This study provides some evidence of an association between MD and dietary intake. Our study highlights the importance of adequate adjustments for BMI in studies of diet and MD.
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Hormone therapy use and mammographic density in postmenopausal Norwegian women.
Breast Cancer Res. Treat.
PUBLISHED: 07-18-2011
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While studies have shown that use of postmenopausal hormone therapy with estrogen and progestogen (EPT) increases mammographic density, aspects of this association remain unclear. We examined whether mammographic density differed by type of hormone therapy (HT) used, dose, duration of use, time since last use, and whether the effects are modified by age and body mass index (BMI). Using a cross-sectional design, we recruited 2,424 postmenopausal women aged 50-69 years participating in the Norwegian Breast Cancer Screening Program. Mammographic density was assessed with a computer-assisted method, and we estimated mean absolute and percent mammographic density through multiple linear regression, and adjusting for possible confounders. Mammographic density was higher among current HT users (percent density: 22.6%; 95% CI: 22.1-23.2%) than among former (17.7%; 17.2-18.2%) or never users (16.3%; 15.7-16.8%). The highest density was seen in current EPT users of high-dose norethisterone acetate (NETA) regimens who had a percent density of 26.2% (24.3-28.1%). Results differed when considering the combined effect of age and BMI. The effect of EPT on mammographic density was modified by age and BMI, with no apparent association among the youngest women (aged 50-55) with the highest BMI (BMI ? 26). A higher mammographic density was found in EPT users compared to never HT users, particularly in women using high-dose NETA regimens. Age and BMI modified the association between EPT use and mammographic density.
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Gene expression profiles of breast biopsies from healthy women identify a group with claudin-low features.
BMC Med Genomics
PUBLISHED: 07-15-2011
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Increased understanding of the variability in normal breast biology will enable us to identify mechanisms of breast cancer initiation and the origin of different subtypes, and to better predict breast cancer risk.
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Age-specific effects of hormone therapy use on overall mortality and ischemic heart disease mortality among women in the California Teachers Study.
Menopause
PUBLISHED: 06-10-2011
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Although the Womens Health Initiative trial suggested that menopausal hormone therapy (HT) does not reduce coronary heart disease mortality overall, subsequent results have suggested that there may be a benefit in younger women. The California Teachers Study questionnaire and mortality data were used to examine whether age modified the association between HT and the relative risk of overall mortality and ischemic heart disease deaths.
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Oral contraceptive formulation and risk of breast cancer.
Contraception
PUBLISHED: 05-27-2011
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While evidence on the association between oral contraceptive (OC) use and breast cancer generally suggests little or no increased risk, the question of whether breast cancer risk varies by OC formulation remains controversial. Few studies have examined this issue because large samples and extensive OC histories are required.
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Oral contraceptive use and survival in women with invasive breast cancer.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 05-06-2011
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Oral contraceptives (OC) are widely used in the United States. Although the relation between OC use and breast cancer incidence has been widely studied, the few studies examining associations between OC use prior to breast cancer diagnosis and survival are inconsistent.
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Breast cancer incidence trends in Norway--explained by hormone therapy or mammographic screening?
Int. J. Cancer
PUBLISHED: 04-05-2011
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A decline in breast cancer incidence has been observed in several countries after 2002. Reduced use of menopausal hormonal therapy (HT), as a consequence of the publication of results from the Womens Health Initiative, has been argued to be the main reason. In Norway, the governmentally funded Norwegian Breast Cancer Screening Program (NBCSP) was implemented during the same time period as the increased use of HT. This study investigated trends in breast cancer incidence by use of HT and introduction of the screening program. We obtained rates of breast cancer from the Cancer Registry of Norway and sales data of HT preparations from the Norwegian Institute of Public Health. Mammography rates were estimated from published reports. Breast cancer incidence rates increased steadily from 1956 to the end of the 20th century, particularly in women aged 55-69 during 1996-2002 residing in the counties where the NBCSP was first introduced. The rates declined after 2002-2003. HT use increased in 1987-2001, peaking around year 2000. In particular, sales of combined estrogen and progestogen preparations declined after 2002. Among women aged 55-59, rates of hormone receptor positive breast cancers peaked in 2000-2003. No such trend was seen in other age groups. In conclusion, the interpretation of breast cancer incidence trends in Norway from 1987 to 2009 is complicated because the NBCSP was introduced during a period with increasing HT use. Both factors likely contributed to the observed trends, and the role of each may vary across age groups.
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Variations in sex hormone metabolism genes, postmenopausal hormone therapy and risk of endometrial cancer.
Int. J. Cancer
PUBLISHED: 03-31-2011
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We investigated whether variants in sex steroid hormone metabolism genes modify the effect of hormone therapy (HT) on endometrial cancer risk in postmenopausal non-Hispanic white women. A nested case-control study was conducted within the California Teachers Study (CTS). We genotyped htSNPs in six genes involved in the hormone metabolism in 286 endometrial cancer cases and 488 controls. Odds ratio (OR) and 95% confidence interval (CI) were estimated for each haplotype using unconditional logistic regression, adjusting for age. The strongest interaction was observed between duration of estrogen therapy (ET) use and haplotype 1A in CYP11A1 (p(interaction) = 0.0027; p(interaction) = 0.010 after correcting for multiple testing within each gene). The OR for endometrial cancer per copy of haplotype 1A was 2.00 (95% CI: 1.05-3.96) for long-term ET users and 0.90 (95% CI: 0.69-1.18) for never users. The most significant interaction with estrogen-progestin therapy (EPT) was found for two haplotypes on CYP19A1 and EPT use (haplotype 4A, p(interaction) = 0.024 and haplotype 3B, p(interaction) = 0.043). However, neither this interaction, nor the ET or EPT interactions for any other genes, was statistically significant after correction for multiple testing. Variations in CYP11A1 may modify the effect of ET use on risk of postmenopausal endometrial cancer; however, larger studies are needed to explore these findings further.
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The association of polymorphisms in hormone metabolism pathway genes, menopausal hormone therapy, and breast cancer risk: a nested case-control study in the California Teachers Study cohort.
Breast Cancer Res.
PUBLISHED: 03-15-2011
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The female sex steroids estrogen and progesterone are important in breast cancer etiology. It therefore seems plausible that variation in genes involved in metabolism of these hormones may affect breast cancer risk, and that these associations may vary depending on menopausal status and use of hormone therapy.
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Bilateral oophorectomy is not associated with increased mortality: the California Teachers Study.
Fertil. Steril.
PUBLISHED: 02-17-2011
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To investigate the effect of surgical menopause due to bilateral oophorectomy on mortality, in light of evidence that bilateral oophorectomy among premenopausal women rapidly reduces endogenous hormone levels, thereby modifying risks of cardiovascular disease and breast cancer.
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Serum estradiol levels associated with specific gene expression patterns in normal breast tissue and in breast carcinomas.
BMC Cancer
PUBLISHED: 02-16-2011
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High serum levels of estradiol are associated with increased risk of postmenopausal breast cancer. Little is known about the gene expression in normal breast tissue in relation to levels of circulating serum estradiol.
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Mammographic density and risk of breast cancer by adiposity: an analysis of four case-control studies.
Int. J. Cancer
PUBLISHED: 02-14-2011
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The association of mammographic breast density with breast cancer risk may vary by adiposity. To examine effect modification by body mass index (BMI), the authors standardized mammographic density data from four case-control studies (1994-2002) conducted in California, Hawaii and Minnesota and Gifu, Japan. The 1,699 cases and 2,422 controls included 45% Caucasians, 40% Asians and 9% African-Americans. Using ethnic-specific BMI cut points, 34% were classified as overweight and 19% as obese. A single reader assessed density from mammographic images using a computer-assisted method. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) while adjusting for potential confounders. Modest heterogeneity in the relation between percent density and breast cancer risk across studies was observed (p(heterogeneity) = 0.08). Cases had a greater age-adjusted mean percent density than controls: 31.7% versus 28.5%, respectively (p <0.001). Relative to <20 percent density, the ORs for >35 were similar across BMI groups whereas the OR for 20-35 was slightly higher in overweight (OR = 1.69, 95% CI: 1.28, 2.24) and obese (OR = 1.62, 95% CI: 1.12, 2.33) than in normal weight women (OR = 1.49, 95% CI: 1.11, 2.01). Furthermore, limited evidence of effect modification by BMI of the OR per 10% increase in percent density (p(interaction) = 0.06) was observed, including subgroup analyses by menopausal status and in analyses that excluded women at the extremes of the BMI scale. Our findings indicate little, if any, modification by BMI of the effects of breast density on breast cancer risk.
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Menopausal hormone therapy does not influence lung cancer risk: results from the California Teachers Study.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 01-25-2011
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Results from studies examining the association between hormone therapy (HT) and lung cancer risk disagree.
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Does hormone therapy counter the beneficial effects of physical activity on breast cancer risk in postmenopausal women?
Cancer Causes Control
PUBLISHED: 01-07-2011
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Studies consistently demonstrate that physical activity is inversely associated with postmenopausal breast cancer. Whether this association is stronger among non-hormone users or former users of menopausal hormone therapy (HT) is of interest given the marked decline in HT use since 2002. The Womens Contraceptive and Reproductive Experiences Study, a population-based case-control study of invasive breast cancer, recruited white women and black women ages 35-64 years and collected histories of lifetime recreational physical activity and HT use including estrogen-alone therapy (ET) and estrogen plus progestin therapy (EPT). Among postmenopausal women (1,908 cases, 2,013 control participants), breast cancer risk declined with increasing levels of lifetime physical activity among never HT users; among short-term HT users (fewer than 5 years); and among current ET users; P (trend) values ranged from 0.004 to 0.016. In contrast, physical activity had no significant association with risk among long-term and past HT users and among current EPT users. No statistical evidence of heterogeneity was demonstrated for duration or currency of HT use. Breast cancer risk decreases with increasing lifetime physical activity levels among postmenopausal women who have not used HT, have used HT for less than 5 years, or are current ET users, yet this study was unable to demonstrate statistically that HT use modifies the relationship between physical activity and breast cancer. With profound changes in HT use occurring since 2002, it will be important in future studies to learn whether or not any association between physical activity and breast cancer among former HT users is a function of time since last HT use.
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Breast cancer risk and ovariectomy, hysterectomy, and tubal sterilization in the womens contraceptive and reproductive experiences study.
Am. J. Epidemiol.
PUBLISHED: 11-25-2010
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Removal or impairment of ovaries before menopause may affect a womans breast cancer risk by altering her cumulative exposure to ovarian hormones. The Womens Contraceptive and Reproductive Experiences Study, a population-based, multicenter case-control study of incident invasive breast cancer, recruited women aged 35-64 years (4,490 cases and 4,611 controls) who provided data on ovariectomy, hysterectomy, and tubal sterilization during in-person interviews. Controls were frequency-matched to cases by age, race, and study site. Unconditional logistic regression analysis was used. Women who had not undergone premenopausal reproductive surgery were the referent group. Bilateral ovariectomy was associated with reduced breast cancer risk overall (odds ratio (OR) = 0.59, 95% confidence interval (CI): 0.50, 0.69) and among women <45 years of age (ORs ranged from 0.31 to 0.52), but not among those who were older at surgery. It was also associated with a reduced risk for estrogen and progesterone receptor-positive tumors (OR = 0.63, 95% CI: 0.52, 0.75) but not receptor-negative tumors. Hysterectomy with ovarian conservation (OR = 0.83, 95% CI: 0.72, 0.96) and hysterectomy with partial ovary removal (OR = 0.73, 95% CI: 0.59, 0.91) were also associated with lower risk. No association with breast cancer risk was observed with tubal sterilization only or partial ovariectomy without hysterectomy. Reproductive organ surgeries may alter ovarian hormone levels, thereby affecting breast cancer risk.
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Alcohol consumption over time and risk of lymphoid malignancies in the California Teachers Study cohort.
Am. J. Epidemiol.
PUBLISHED: 10-15-2010
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Several previous studies found inverse associations between alcohol consumption and risk of non-Hodgkin lymphoma (NHL) and multiple myeloma. However, most studies were retrospective, and few distinguished former drinkers or infrequent drinkers from consistent nondrinkers. Therefore, the authors investigated whether history of alcohol drinking affected risks of NHL and multiple myeloma among 102,721 eligible women in the California Teachers Study, a prospective cohort study in which 496 women were diagnosed with B-cell NHL and 101 were diagnosed with multiple myeloma between 1995-1996 and December 31, 2007. Incidence rate ratios and 95% confidence intervals were estimated using Cox proportional hazards regression. Risk of all types of B-cell NHL combined or multiple myeloma was not associated with self-reported past consumption of alcohol, beer, wine, or liquor at ages 18-22 years, at ages 30-35 years, or during the year before baseline. NHL subtypes were inconsistently associated with alcohol intake. However, women who were former alcohol drinkers at baseline were at elevated risk of overall B-cell NHL (rate ratio = 1.46, 95% confidence interval: 1.08, 1.97) and follicular lymphoma (rate ratio = 1.81, 95% confidence interval: 1.00, 3.28). The higher risk among former drinkers emphasizes the importance of classifying both current and past alcohol consumption and suggests that factors related to quitting drinking, rather than alcohol itself, may increase B-cell NHL risk.
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Menopausal hormone therapy and subsequent risk of specific invasive breast cancer subtypes in the California Teachers Study.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 08-10-2010
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Although it is well established that combined estrogen-progestin therapy (EPT) increases breast cancer risk, questions remain regarding the effect of different formulations of hormones, whether certain women are at particularly high risk, and whether risk varies by tumor subtype.
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Expression levels of uridine 5-diphospho-glucuronosyltransferase genes in breast tissue from healthy women are associated with mammographic density.
Breast Cancer Res.
PUBLISHED: 08-05-2010
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Mammographic density (MD), as assessed from film screen mammograms, is determined by the relative content of adipose, connective and epithelial tissue in the female breast. In epidemiological studies, a high percentage of MD confers a four to six fold risk elevation of developing breast cancer, even after adjustment for other known breast cancer risk factors. However, the biologic correlates of density are little known.
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Meat consumption, nonsteroidal anti-inflammatory drug use, and mortality among colorectal cancer patients in the California Teachers Study.
Cancer Prev Res (Phila)
PUBLISHED: 06-15-2010
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A low-meat diet and regular use of nonsteroidal anti-inflammatory drugs (NSAID) have been associated with decreased mortality among colorectal cancer (CRC) patients. Here, we investigated the association between prediagnosis usual meat consumption and CRC-specific mortality, and whether meat consumption modifies the previously noted association between NSAID use and CRC-specific mortality among women in the California Teachers Study cohort. Women joining the California Teachers Study in 1995-1996 without prior CRC diagnosis, diagnosed with incident CRC during follow-up through December 2007, were eligible for inclusion. Meat intake (frequency and serving size) and NSAID use (aspirin or ibuprofen use) were ascertained via self-administered questionnaires before diagnosis. Vital status and cause of death were determined by linkage with mortality files. Multivariable Cox proportional hazards regression models were used to estimate hazard ratios for death and 95% confidence intervals. Prediagnosis meat consumption was not associated with CRC-specific mortality among 704 CRC patients (and 201 CRC-specific deaths), comparing patients in the lowest consumption tertile (0-5.4 medium-sized servings/wk) to those in the higher consumption tertiles. Regular NSAID use (1-3 times/wk, 4-6 times/wk, daily) versus none was associated with decreased CRC-specific mortality among patients in the lowest meat consumption tertile (hazard ratio, 0.22; 95% CI, 0.06-0.82), but not among patients in the higher meat intake tertiles. The previously observed mortality risk reduction among female CRC patients associated with regular NSAID use was restricted to patients who reported low meat intake before diagnosis. These findings have implications for CRC survivorship and tertiary CRC prevention.
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Genetic variation in the progesterone receptor gene and risk of endometrial cancer: a haplotype-based approach.
Carcinogenesis
PUBLISHED: 06-13-2010
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It is well established that estrogen increases endometrial cancer risk, whereas progesterone opposes the estrogen effects. The PROGINS allele of the progesterone receptor (PGR) gene reduces the function of PGR and has been associated with increased risk of the endometrioid type ovarian cancer. We investigated whether genetic variation in PGR is also associated with endometrial cancer risk using a haplotype-based approach.
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A case-control study of body mass index and breast cancer risk in white and African-American women.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 05-25-2010
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Large body size has been associated with decreased risk of breast cancer in premenopausal women but with increased risk in postmenopausal women. Limited information is available about African-American women and differences by estrogen and progesterone receptor status.
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Hypertension, antihypertensive medication use, and breast cancer risk in the California Teachers Study cohort.
Cancer Causes Control
PUBLISHED: 05-18-2010
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We investigated the association between hypertension, antihypertensive (AH) medication use, and breast cancer in a large prospective study, the California Teachers Study (CTS).
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Influence of individual and combined health behaviors on total and cause-specific mortality in men and women: the United Kingdom health and lifestyle survey.
Arch. Intern. Med.
PUBLISHED: 04-28-2010
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Physical activity, diet, smoking, and alcohol consumption have been shown to be related to mortality. We examined prospectively the individual and combined influence of these risk factors on total and cause-specific mortality.
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Body size and the risk of endometrial cancer by hormone therapy use in postmenopausal women in the California Teachers Study cohort.
Cancer Causes Control
PUBLISHED: 04-10-2010
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To investigate whether hormone therapy (HT) and obesity are associated with endometrial cancer risk among postmenopausal women in the California Teachers Study cohort.
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Pregnancy-related factors and the risk of breast carcinoma in situ and invasive breast cancer among postmenopausal women in the California Teachers Study cohort.
Breast Cancer Res.
PUBLISHED: 04-01-2010
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Although pregnancy-related factors such as nulliparity and late age at first full-term pregnancy are well-established risk factors for invasive breast cancer, the roles of these factors in the natural history of breast cancer development remain unclear.
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Hormone therapy and fatal breast cancer.
Pharmacoepidemiol Drug Saf
PUBLISHED: 03-26-2010
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Among unanswered questions is whether menopausal use of estrogen therapy (ET) or estrogen-plus-progestin therapy (CHT) increases risk of developing fatal breast cancer i.e., developing and dying of breast cancer. Using a population-based case-control design, we estimated incidence rate ratios of fatal breast cancer in postmenopausal hormone therapy (HT) users compared to non-users by type, duration, and recency of HT use.
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Body size and the risk of ovarian cancer by hormone therapy use in the California Teachers Study cohort.
Cancer Causes Control
PUBLISHED: 03-24-2010
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To investigate whether obesity and hormone therapy (HT) are associated with ovarian cancer risk among women in the California Teachers Study cohort.
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Fine scale mapping of the breast cancer 16q12 locus.
Hum. Mol. Genet.
PUBLISHED: 03-23-2010
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Recent genome-wide association studies have identified a breast cancer susceptibility locus on 16q12 with an unknown biological basis. We used a set of single nucleotide polymorphism (SNP) markers to generate a fine-scale map and narrowed the region of association to a 133 kb DNA segment containing the largely uncharacterized hypothetical gene LOC643714, a short intergenic region and the 5 end of TOX3. Re-sequencing this segment in European subjects identified 293 common polymorphisms, including a set of 26 highly correlated candidate causal variants. By evaluation of these SNPs in five breast cancer case-control studies involving more than 23 000 subjects from populations of European and Southeast Asian ancestry, all but 14 variants could be excluded at odds of <1:100. Most of the remaining variants lie in the intergenic region, which exhibits evolutionary conservation and open chromatin conformation, consistent with a regulatory function. African-American case-control studies exhibit a different pattern of association suggestive of an additional causative variant.
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Genotypes and haplotypes in the insulin-like growth factors, their receptors and binding proteins in relation to plasma metabolic levels and mammographic density.
BMC Med Genomics
PUBLISHED: 03-19-2010
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Increased mammographic density is one of the strongest independent risk factors for breast cancer. It is believed that one third of breast cancers are derived from breasts with more than 50% density. Mammographic density is affected by age, BMI, parity, and genetic predisposition. It is also greatly influenced by hormonal and growth factor changes in a womans life cycle, spanning from puberty through adult to menopause. Genetic variations in genes coding for hormones and growth factors involved in development of the breast are therefore of great interest. The associations between genetic polymorphisms in genes from the IGF pathway on mammographic density and circulating levels of IGF1, its binding protein IGFBP3, and their ratio in postmenopausal women are reported here.
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Evaluation of established breast cancer risk factors as modifiers of BRCA1 or BRCA2: a multi-center case-only analysis.
Breast Cancer Res. Treat.
PUBLISHED: 03-05-2010
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The incomplete penetrance of mutations in BRCA1 and BRCA2 suggests that some combination of environmental and genetic factors modifies the risk of breast cancer in mutation carriers. This study sought to identify possible interactions between established breast cancer risk factors and BRCA1 or BRCA2 mutations using a case-only study design. Breast cancer cases that had been tested for BRCA1 and BRCA2 mutations were identified from 11 collaborating centers. Comparisons of reproductive and lifestyle risk factors were made between women with breast cancer who were positive for BRCA1 mutations (n = 283), BRCA2 mutations (n = 204), or negative for both BRCA1 and BRCA2 mutations (n = 894). Interaction risk ratios (IRRs) were calculated using multinominal logistic regression models. Compared with non-carriers, statistically significant IRRs were observed for later age at menarche among BRCA2 mutation carriers, for a greater number of pregnancies among both BRCA1 and BRCA2 mutation carriers, and for alcohol use among BRCA1 mutation carriers. Our data suggest that the risk for breast cancer among BRCA1 or BRCA2 carriers may be modified by reproductive characteristics and alcohol use. However, our results should be interpreted cautiously given the overall inconsistency in the epidemiologic literature on modifiers of BRCA1 and BRCA2.
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Long-term postmenopausal hormone therapy and endometrial cancer.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 01-19-2010
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Estrogen-alone therapy (ET) or estrogen and progestin (EPT) as menopausal hormone therapy (HT) has been commonly used to alleviate menopausal symptoms. Treatments containing > or = 10 days per month of progestin are considered relatively safe with respect to endometrial cancer risk. However, the endometrial safety of long-term EPT regimens is uncertain. We conducted a case-control study of 311 invasive endometrial cancer cases and 570 controls nested within the California Teachers Study cohort. We used unconditional logistic regression to obtain odds ratios (OR) and 95% confidence intervals (95% CI) for the association between long-term HT use and endometrial cancer risk, and to assess the modifying effect of body mass index (BMI). Long-term (> or = 10 years) use of ET, sequential EPT with <10 days per month progestin, and continuous-combined EPT (> or = 25 days/month progestin) were all associated with an elevated risk of endometrial cancer (OR, 4.5; 95% CI, 2.5-8.1; OR, 4.4; 95% CI, 1.7-11.2; and OR, 2.1; 95% CI, 1.3-3.3, respectively; all P(trend) < 0.001). The risk associated with short-term use was elevated only for ET preparations. The association for continuous-combined EPT was confined to thinner women (BMI, <25 kg/m2; P(interaction) = 0.03). Among heavier women (BMI, > or = 25 kg/m2), use of continuous-combined EPT was associated with a statistically nonsignificant reduction in risk. These findings confirm that long-term use of ET, sequential EPT, or, among normal weight women, continuous-combined EPT is associated with increased risk of endometrial cancer.
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Use of four biomarkers to evaluate the risk of breast cancer subtypes in the womens contraceptive and reproductive experiences study.
Cancer Res.
PUBLISHED: 01-12-2010
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Epidemiologic studies suggest that some hormone-related risk factors in breast cancer differentially influence risk for disease subtypes classified by the status of the estrogen and progesterone receptors (ER/PR). However, it remains unclear whether human epidermal growth factor receptor 2 (HER2) or p53 expression status further differentiates these exposure-risk group associations. We evaluated the associations of oral contraceptive (OC) use and reproductive factors with incident invasive breast cancer subtypes among 1,197 population-based cases and 2,015 controls from the Los Angeles County or Detroit components of the Womens Contraceptive and Reproductive Experiences Study. Case-control comparisons by ER/PR/HER2/p53 status were conducted by multivariable polychotomous unconditional logistic regression methods. We found that OC use was not associated with any breast cancer subtype as defined by ER/PR/HER2/p53 status, except for a 2.9-fold increased risk of so-called triple-negative tumors (ER(-)/PR(-)/HER2(-)) among women of 45 to 64 years of age who started OC use before age 18. Parity was associated with a decreased risk of luminal A (ER(+) or PR(+), HER2(-)), luminal B (ER(+) or PR(+)/HER2(+)), and ER(-)/PR(-)/HER2(+) tumors. Age at first full-term pregnancy was positively associated with luminal A tumors among older women. Neither of these reproductive factors was associated with triple-negative tumors. Long duration of breast-feeding lowered the risk of triple-negative and luminal A tumors. p53 status did not define further differential risk patterns. Our findings offer evidence of differences in the hormone-related risk factors between triple-negative cancers and other ER/PR/HER2-defined subtypes of breast cancer.
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Recent breast cancer incidence trends according to hormone therapy use: the California Teachers Study cohort.
Breast Cancer Res.
PUBLISHED: 01-08-2010
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Recent, international declines in breast cancer incidence are unprecedented, and the causes remain controversial. Few data sources can address breast cancer incidence trends according to pertinent characteristics like hormone therapy use history.
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Risk factors for surgically removed fibroids in a large cohort of teachers.
Fertil. Steril.
PUBLISHED: 11-05-2009
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To describe reproductive and lifestyle correlates of surgically confirmed fibroids.
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Long-term and recent recreational physical activity and survival after breast cancer: the California Teachers Study.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 10-20-2009
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Long-term physical activity is associated with lower breast cancer risk. Little information exists on its association with subsequent survival.
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An admixture scan in 1,484 African American women with breast cancer.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 10-20-2009
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African American women with breast cancer present more commonly with aggressive tumors that do not express the estrogen receptor (ER) and progesterone receptor (PR) compared with European American women. Whether this disparity is the result of inherited factors has not been established. We did an admixture-based genome-wide scan to search for risk alleles for breast cancer that are highly differentiated in frequency between African American and European American women, and may contribute to specific breast cancer phenotypes, such as ER-negative (ER-) disease. African American women with invasive breast cancer (n = 1,484) were pooled from six population-based studies and typed at approximately 1,500 ancestry-informative markers. We investigated global genetic ancestry and did a whole genome admixture scan searching for breast cancer-predisposing loci in association with disease phenotypes. We found a significant difference in ancestry between ER+PR+ and ER-PR- women, with higher European ancestry among ER+PR+ individuals, after controlling for possible confounders (odds ratios for a 0 to 1 change in European ancestry proportion, 2.84; 95% confidence interval, 1.13-7.14; P = 0.026). Women with localized tumors had higher European ancestry than women with non-localized tumors (odds ratios, 2.65; 95% confidence interval, 1.11-6.35; P = 0.029). No genome-wide statistically significant associations were observed between European or African ancestry at any specific locus and breast cancer, or in analyses stratified by ER/PR status, stage, or grade. In summary, in African American women, genetic ancestry is associated with ER/PR status and disease stage. However, we found little evidence that genetic ancestry at any one region contributes significantly to breast cancer risk or hormone receptor status.
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Nonsteroidal anti-inflammatory drugs: effects on mortality after colorectal cancer diagnosis.
Cancer
PUBLISHED: 10-15-2009
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Nonsteroidal anti-inflammatory drug (NSAID) use has been associated with a decreased colorectal cancer (CRC) risk. However, to the best of the authors knowledge, the effects of NSAID on clinical outcomes after CRC diagnosis are not well defined. The authors investigated the association between prediagnosis NSAID use and mortality after CRC diagnosis among women in the California Teachers Study cohort.
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Body size, recreational physical activity, and B-cell non-Hodgkin lymphoma risk among women in the California teachers study.
Am. J. Epidemiol.
PUBLISHED: 10-12-2009
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Nutritional status and physical activity are known to alter immune function, which may be relevant to lymphomagenesis. The authors examined body size measurements and recreational physical activity in relation to risk of B-cell non-Hodgkin lymphoma (NHL) in the prospective California Teachers Study. Between 1995 and 2007, 574 women were diagnosed with incident B-cell NHL among 121,216 eligible women aged 22-84 years at cohort entry. Multivariable-adjusted relative risks and 95% confidence intervals were estimated by fitting Cox proportional hazards models for all B-cell NHL combined and for the 3 most common subtypes: diffuse large B-cell lymphoma, follicular lymphoma, and B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma. Height was positively associated with risk of all B-cell NHLs (for >1.70 vs. 1.61-1.65 m, relative risk = 1.50, 95% confidence interval: 1.16, 1.96) and chronic lymphocytic leukemia/small lymphocytic lymphoma (relative risk = 1.93, 95% confidence interval: 1.09, 3.41). Weight and body mass index at age 18 years were positive predictors of B-cell NHL risk overall. These findings indicate that greater height, which may reflect genetics, early life immune function, infectious exposures, nutrition, or growth hormone levels, may play a role in NHL etiology. Adiposity at age 18 years may be more relevant to NHL etiology than that in later life.
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Ethnic differences in the use of regular mammography: the multiethnic cohort.
Breast Cancer Res. Treat.
PUBLISHED: 10-01-2009
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Womens regular use of mammography over a 6 year interval was examined among women aged 45-75 in the Hawaii and Los Angeles Multiethnic Cohort (MEC). The analyses included 81,722 African American, Japanese, Latina, Native Hawaiian, and White females using self-reported mammography history from 1993 to 1998. Ninety-one percent of MEC women reported ever having a mammogram, however only 36% reported regular annual and 48% reported regular biennial mammography over the interval. Mammography was lowest among women who were obese, had a high school education or less, or who were aged 70 and over. Regular mammography use during follow-up was low compared to prior studies reporting on recent mammography. African American, Latina, and Native Hawaiian women had significantly lower annual and biennial mammography use compared to White women even after controlling for age, education, family history, body mass index and hormone therapy indicating that gaps exist in mammography that remain unexplained by known predictors of screening behavior.
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Breast cancer receptor status: do results from a centralized pathology laboratory agree with SEER registry reports?
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 08-08-2009
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We investigated the extent to which estrogen receptor (ER) and progesterone receptor (PR) status results from a centralized pathology laboratory agree with ER and PR results from community pathology laboratories reported to two Surveillance, Epidemiology and End Results (SEER) registries (Los Angeles County and Detroit) and whether statistical estimates for the association between reproductive factors and breast cancer receptor subtypes differ by the source of data. The agreement between the centralized laboratory and SEER registry classifications was substantial for ER (kappa = 0.70) and nearly so for PR status (kappa = 0.60). Among the four subtypes defined by joint ER and PR status, the agreement between the two sources was substantial for the two major breast cancer subtypes (ER-/PR-, kappa = 0.69; ER+/PR+, kappa = 0.62) and poor for the two rarer subtypes (ER+/PR-, kappa = 0.30; ER-/PR+, kappa = 0.05). Estimates for the association between reproductive factors (number of full-term pregnancies, age at first full-term pregnancy, and duration of breastfeeding) and the two major subtypes (ER+/PR+ and ER-/PR-) differed minimally between the two sources of data. For example, parous women with at least four full-term pregnancies had 40% lower risk for ER+/PR+ breast cancer than women who had never been pregnant [centralized laboratory, odds ratio, 0.60 (95% confidence interval, 0.39-0.92); SEER, odds ratio, 0.57 (95% confidence interval, 0.38-0.85)]; no association was observed for ER-/PR- breast cancer (both P(trend) > 0.30). Our results suggest that conclusions based on SEER registry data are reasonably reliable for ER+/PR+ and ER-/PR- subtypes.
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Admixture mapping of 15,280 African Americans identifies obesity susceptibility loci on chromosomes 5 and X.
PLoS Genet.
PUBLISHED: 04-22-2009
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The prevalence of obesity (body mass index (BMI) > or =30 kg/m(2)) is higher in African Americans than in European Americans, even after adjustment for socioeconomic factors, suggesting that genetic factors may explain some of the difference. To identify genetic loci influencing BMI, we carried out a pooled analysis of genome-wide admixture mapping scans in 15,280 African Americans from 14 epidemiologic studies. Samples were genotyped at a median of 1,411 ancestry-informative markers. After adjusting for age, sex, and study, BMI was analyzed both as a dichotomized (top 20% versus bottom 20%) and a continuous trait. We found that a higher percentage of European ancestry was significantly correlated with lower BMI (rho = -0.042, P = 1.6x10(-7)). In the dichotomized analysis, we detected two loci on chromosome X as associated with increased African ancestry: the first at Xq25 (locus-specific LOD = 5.94; genome-wide score = 3.22; case-control Z = -3.94); and the second at Xq13.1 (locus-specific LOD = 2.22; case-control Z = -4.62). Quantitative analysis identified a third locus at 5q13.3 where higher BMI was highly significantly associated with greater European ancestry (locus-specific LOD = 6.27; genome-wide score = 3.46). Further mapping studies with dense sets of markers will be necessary to identify the alleles in these regions of chromosomes X and 5 that may be associated with variation in BMI.
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FGFR2 variants and breast cancer risk: fine-scale mapping using African American studies and analysis of chromatin conformation.
Hum. Mol. Genet.
PUBLISHED: 02-17-2009
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Genome-wide association studies have identified FGFR2 as a breast cancer (BC) susceptibility gene in populations of European and Asian descent, but a causative variant has not yet been conclusively identified. We hypothesized that the weaker linkage disequilibrium across this associated region in populations of African ancestry might help refine the set of candidate-causal single nucleotide polymorphisms (SNPs) previously identified by our group. Eight candidate-causal SNPs were evaluated in 1253 African American invasive BC cases and 1245 controls. A significant association with BC risk was found with SNP rs2981578 (unadjusted per-allele odds ratio = 1.20, 95% confidence interval 1.03-1.41, P(trend) = 0.02), with the odds ratio estimate similar to that reported in European and Asian subjects. To extend the fine-mapping, genotype data from the African American studies were analyzed jointly with data from European (n = 7196 cases, 7275 controls) and Asian (n = 3901 cases, 3205 controls) studies. In the combined analysis, SNP rs2981578 was the most strongly associated. Five other SNPs were too strongly correlated to be excluded at a likelihood ratio of < 1/100 relative to rs2981578. Analysis of DNase I hypersensitive sites indicated that only two of these map to highly accessible chromatin, one of which, SNP rs2981578, has previously been implicated in up-regulating FGFR2 expression. Our results demonstrate that the association of SNPs in FGFR2 with BC risk extends to women of African American ethnicity, and illustrate the utility of combining association analysis in datasets of diverse ethnic groups with functional experiments to identify disease susceptibility variants.
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Is there a difference in the association between percent mammographic density and subtypes of breast cancer? Luminal A and triple-negative breast cancer.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 02-03-2009
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Mammographic density is a potentially modifiable risk factor for breast cancer. To what extent mammographic density is a predictor for both hormone receptor-positive and hormone receptor-negative tumors is unclear. Even less is known about whether mammographic density predicts subtypes of breast cancer defined by expression status of the three receptors: estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2).
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Two estrogen-related variants in CYP19A1 and endometrial cancer risk: a pooled analysis in the Epidemiology of Endometrial Cancer Consortium.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 01-07-2009
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Common variants in CYP19A1 (the A alleles of rs749292 and rs727479) have been associated with a 10% to 20% increase in circulating estrogen levels in postmenopausal women. We hypothesized that the presence of one or both A alleles in these single nucleotide polymorphisms (SNP) is associated with increased endometrial cancer risk. We tested this hypothesis in a large pooled analysis of 4,998 endometrial cancer cases and 8,285 controls from 10 studies in the Epidemiology of Endometrial Cancer Consortium. The majority of women (>66%) were whites, with smaller proportions of other races and ethnic groups (blacks, Asians, and Latinas) also included in this pooled analysis. Unconditional logistic regression was used to model the association between SNPs/haplotypes and endometrial cancer risk. Carrying the A allele of either of these SNPs was associated with an increased risk of endometrial cancer, with pooled odds ratios per allele of 1.14, 95% confidence interval of 1.09-1.21, and P = 7.1 x 10(-7) for rs749292, and odds ratio per allele of 1.08, 95% confidence interval of 1.02-1.14, and P = 0.009 for rs727479. For rs749292, these associations were generally stronger among women age >or=55 years. For both SNPs, risk increased with increasing body mass index, and for rs727479, this pattern seemed stronger among women age >or=55 years (P interaction = 0.007). The combination of A alleles in the two SNPs, either by direct count or by haplotype analysis, did not increase risk above that observed for the individual SNPs. Our study provides evidence that CYP19A1 genetic variation influences susceptibility to endometrial cancer, particularly among older and obese women.
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The relative importance of genetics and environment on mammographic density.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 01-07-2009
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Although several environmental factors predict mammographic density, estimates of its heritability have been quite high. We investigated whether part of the presumed heritability might be attributed to differential sharing of modifiable risk factors in monozygotic (MZ) and dizygotic (DZ) twins.
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Physical activity and mammographic density in a cohort of postmenopausal Norwegian women; a cross-sectional study.
Springerplus
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Mammographic density (MD) is a strong risk factor for breast cancer and may represent a useful intermediate marker for breast cancer risk. Physical activity (PA) is known to be associated with a reduced risk of breast cancer. If PA is associated with MD then this would be useful for breast cancer prevention studies. MD was assessed on digitized mammograms using a computer assisted method (Madena) in 2218 postmenopausal women. A questionnaire assessed PA, by asking about the duration and intensity of light, moderate, strenuous PA/week. We used multivariate linear regression models to estimate least square means of percent MD by total and intensity of PA with adjustment for confounders. The mean age (± s.d) was 58.4 (±5.3) and mean BMI was 24.6 (±4.6). We observed a statistically significant inverse association between total PA and MD in the over-weight (BMI?=?25.0-29.9) women, where mean MD among women with highest activity (>360 mins/week) was 12.6% (95%CI; 11.2%-14.0%), while among women with no activity it was 15.9% (95 CI; 13.6%-18.2%, p for trend?=?0.04). There was no association in the other BMI strata. MD was 12.1% (11.2%-13.0%) in the highest group (> 180 mins/week) of moderate/strenuous activity and in the no activity group 14.8% (14.2%-15.5%, p for trend?=?0.001) in the over-weight women. There was no association between light PA and MD in all women combined or in any other BMI strata. We found some evidence of an inverse association between PA and MD among overweight women.
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Mammographic screening debate on study design: a need to move the field forward.
BMC Med
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The mammographic screening debate has been running for decades. The temperature of this debate is unusually high, and all participants, regardless of viewpoint, seem to have a conflict of interest. Another unusual aspect of this debate is the focus on study design, and in particular on designs that some think exceeded their usefulness decades ago. What are the questions that remain to be answered in this debate? Are there methodological issues that have not been adequately addressed? Do we have the right tools to provide up-to-date answers to how women can best protect themselves against dying from breast cancer? This commentary discusses some of the current issues.See related Opinion articles http://www.biomedcentral.com/1741-7015/10/106 and http://www.biomedcentral.com/1741-7015/10/163.
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Mammographic density and inter-observer variability of pathologic evaluation of core biopsies among women with mammographic abnormalities.
BMC Cancer
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As high percentage of mammographic densities complicates the assessment of imaging findings, mammographic density may influence the histopathological evaluation of core-biopsies of the breast. We measured the influence of mammographic density on the inter-observer variability of histopathological findings of breast biopsies.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.