| 1. |
- Ahearn, Thomas U., et al.
(author)
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Common variants in breast cancer risk loci predispose to distinct tumor subtypes
- 2022
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In: Breast Cancer Research. - : Springer Nature. - 1465-5411 .- 1465-542X. ; 24:1
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Journal article (peer-reviewed)abstract
- BackgroundGenome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear.MethodsAmong 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes.ResultsEighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions.ConclusionThis report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction.
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| 2. |
- Ahrens, Wolfgang, et al.
(author)
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Occupational exposure to endocrine-disrupting compounds and biliary tract cancer among men
- 2007
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In: Scandinavian Journal of Work, Environment and Health. - : Scandinavian Journal of Work, Environment and Health. - 0355-3140 .- 1795-990X. ; 33:5, s. 387-396
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Journal article (peer-reviewed)abstract
- Objectives This study investigated the association between cancer of the extrahepatic biliary tract and exposure to endocrine-disrupting compounds. Methods Altogether 183 men with histologically confirmed carcinoma of the extrahepatic biliary tract and 1938 matched controls were interviewed between 1995 and 1997 in the frame of an international multicenter case-control study in six European countries (Denmark, France, Germany, Italy, Spain, and Sweden). Selfreported job descriptions were converted to semiquantitative variables (intensity, probability, and duration of exposure) for 14 endocrine-disrupting compounds. The cases were compared with 1421 population controls and 517 colon adenocarcinoma patients. Odds ratios (OR) and 95% confidence intervals (95% CI) were obtained with unconditional logistic regression and adjusted for age, country, and gallstones. Results Occupational exposure to endocrine-disrupting compounds resulted in an OR of 1.4 (95% CI 1.0-2. 1) with no dose-effect relationship for cumulative exposure (low: OR 1.3, 95% CI 0.6-3.0; medium: OR 1.5, 95% CI0.8-2.7; high: OR 1.4, 95% CI 0.9-2.4) (only index participants). The elevated risk was restricted to extrahepatic bile ducts and ampulla Vateri (OR 1.7, 95% CI 1.0-2.6). The adjusted OR for cancer of the extrahepatic biliary tract after exposure to polychlorinated biphenyls was 2.8 (95% CI 1.3-5.9, only index participants). Conclusions The data show some associations between exposure to endocrine-disrupting compounds in the workplace and the risk for cancer of the extrahepatic biliary tract among men, particularly for the extrahepatic bile duct and ampulla of Vater. Polychlorinated biphenyls could possibly be a strong risk factor.
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| 3. |
- Ahrens, Wolfgang, et al.
(author)
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Risk factors for extrahepatic biliary tract carcinoma in men: medical conditions and lifestyle: results from a European multicentre case-control study
- 2007
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In: European Journal of Gastroenterology and Hepathology. - 1473-5687. ; 19:8, s. 623-630
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To identify risk factors of carcinoma of the extrahepatic biliary tract in men. METHODS: Newly diagnosed and histologically confirmed patients, 35-70 years old, were interviewed between 1995 and 1997 in Denmark, Sweden, France, Germany and Italy. Population controls were frequency-matched by age and region. Adjusted odds ratios and 95%-confidence intervals were estimated by logistic regression. RESULTS: The analysis included 153 patients and 1421 controls. The participation proportion was 71% for patients and 61% for controls. Gallstone disease was corroborated as a risk factor for extrahepatic biliary tract carcinoma in men (odds ratio 2.49; 95% confidence interval 1.32-4.70), particularly for gall bladder tumors (odds ratio 4.68; 95% confidence interval 1.85-11.84). For a body mass index [height (m) divided by squared weight (kg2)] >30 at age 35 years, an excess risk was observed (odds ratio 2.58; 95% confidence interval 1.07-6.23, reference: body mass index 18.5-25) that was even stronger if the body mass index was >30 for the lowest weight in adulthood (odds ratio 4.68; 95% confidence interval 1.13-19.40). Infection of the gall bladder, chronic inflammatory bowel disease, hepatitis or smoking showed no clear association, whereas some increase in risk was suggested for consumption of 40-80 g alcohol per day and more. CONCLUSIONS: Our study corroborates gallstones as a risk indicator in extrahepatic biliary tract carcinoma. Permanent overweight and obesity in adult life was identified as a strong risk factor for extrahepatic biliary tract carcinoma, whereas we did not find any strong lifestyle-associated risk factors. Inconsistent results across studies concerning the association of extrahepatic biliary tract carcinoma with overweight and obesity may be explained by the different approaches to assess this variable.
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| 4. |
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| 5. |
- Cook, Michael B, et al.
(author)
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Tobacco and Alcohol in Relation to Male Breast Cancer: An Analysis of the Male Breast Cancer Pooling Project Consortium.
- 2015
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In: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755. ; 24:3, s. 520-531
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Journal article (peer-reviewed)abstract
- Background: The etiology of male breast cancer is poorly understood, partly due to its relative rarity. Although tobacco and alcohol exposures are known carcinogens, their association with male breast cancer risk remains ill-defined. Methods: The Male Breast Cancer Pooling Project consortium provided 2,378 cases and 51,959 controls for analysis from 10 case-control and 10 cohort studies. Individual participant data were harmonized and pooled. Unconditional logistic regression was used to estimate study design-specific (case-control/cohort) odds ratios (OR) and 95% confidence intervals (CI), which were then combined using fixed effects meta-analysis. Results: Cigarette smoking status, smoking pack-years, duration, intensity, and age at initiation were not associated with male breast cancer risk. Relations with cigar and pipe smoking, tobacco chewing, and snuff use were also null. Recent alcohol consumption and average grams of alcohol consumed per day were also not associated with risk; only one sub-analysis of very high recent alcohol consumption (>60 grams/day) was tentatively associated with male breast cancer (ORunexposed referent=1.29, 95%CI:0.97-1.71; OR>0-<7 g/day referent=1.36, 95%CI:1.04-1.77). Specific alcoholic beverage types were not associated with male breast cancer. Relations were not altered when stratified by age or body mass index. Conclusions: In this analysis of the Male Breast Cancer Pooling Project we found little evidence that tobacco and alcohol exposures were associated with risk of male breast cancer. Impact: Tobacco and alcohol do not appear to be carcinogenic for male breast cancer. Future studies should aim to assess these exposures in relation to subtypes of male breast cancer.
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| 6. |
- Escala-Garcia, Maria, et al.
(author)
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A network analysis to identify mediators of germline-driven differences in breast cancer prognosis
- 2020
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In: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 11:1
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Journal article (peer-reviewed)abstract
- Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies similar to 7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis.
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| 7. |
- Guénel, Pascal, et al.
(author)
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Alcohol drinking may increase risk of breast cancer in men : a European population-based case-control study
- 2004
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In: Cancer Causes and Control. - 1573-7225 .- 0957-5243. ; 15:6, s. 80-571
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Journal article (peer-reviewed)abstract
- OBJECTIVE: It has been estimated that alcohol drinking increases the risk of breast cancer in women by approximately 7% for each increment of 10 g alcohol per day. However, the few studies conducted on breast cancer among men have failed to detect an association with quantitative measures of alcohol drinking, even if the alcohol intake is generally higher in men than in women. On the other hand, increased risks of male breast cancer were inconsistently reported in alcoholics or patients with liver cirrhosis. We have investigated the role of alcohol drinking in male breast cancer using data collected in a population-based case-control study on seven rare cancers, conducted in Denmark, France, Germany, Italy, and Sweden.METHODS: The cases were 74 histologically verified male breast cancer patients aged 35-70 years. The controls (n = 1432) were selected from population registers, and frequency-matched to the cases by age group and geographic area. To check for consistency, a separate analysis was conducted using as controls the patients with a rare cancer other than male breast recruited simultaneously in the European study (n = 519 men).RESULTS: Based on population controls, the risk of developing breast cancer in men increased by 16% (95% CI: 7-26%) per 10 g alcohol /day (p < 0.001). An odds ratio of 5.89 (95% CI: 2.21-15.69) was observed for alcohol intake greater than 90 g per day, as compared with light consumers (< 15 g per day). Similar associations were observed when other rare cancers patients were used as controls.CONCLUSION: We found that the relative risk of breast cancer in men is comparable to that in women for alcohol intakes below 60 g per day. It continues to increase at high consumption levels not usually studied in women.
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| 8. |
- Jung, Audrey Y, et al.
(author)
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Distinct reproductive risk profiles for intrinsic-like breast cancer subtypes : pooled analysis of population-based studies
- 2022
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In: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 114:12, s. 1706-1719
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Journal article (peer-reviewed)abstract
- BACKGROUND: Reproductive factors have been shown to be differentially associated with risk of estrogen receptor (ER) positive and ER-negative breast cancer. However, their associations with intrinsic-like subtypes are less clear.METHODS: Analyses included up to 23,353 cases, and 71,072 controls pooled from 31 population-based case-control or cohort studies in the Breast Cancer Association Consortium across 16 countries on 4 continents. Polytomous logistic regression was used to estimate the association between reproductive factors and risk of breast cancer by intrinsic-like subtypes (luminal A-like, luminal B-like, luminal B-HER2-like, HER2-enriched-like, and triple-negative) and by invasiveness. All statistical tests were 2-sided.RESULTS: Compared to nulliparous women, parous women had a lower risk of luminal A-like, luminal B-like, luminal B-HER2-like and HER2-enriched-like disease. This association was apparent only after approximately 10 years since last birth and became stronger with increasing time (odds ratio [OR] = 0.59, 95% confidence interval [CI] = 0.49 to 0.71; and OR = 0.36, 95% CI = 0.28 to 0.46; for multiparous women with luminal A-like tumors 20-<25 years after last birth and 45-<50 years after last birth, respectively). In contrast, parous women had a higher risk of triple-negative breast cancer right after their last birth (for multiparous women: OR = 3.12, 95%CI = 2.02 to 4.83) that was attenuated with time but persisted for decades (OR = 1.03, 95%CI = 0.79 to 1.34, for multiparous women 25 to < 30 years after last birth). Older age at first birth (P-heterogeneity<.001 for triple-negative compared to luminal-A like) and breastfeeding (P-heterogeneity<.001 for triple-negative compared to luminal-A like) were associated with lower risk of triple-negative but not with other disease subtypes. Younger age at menarche was associated with higher risk of all subtypes; older age at menopause was associated with higher risk of luminal A-like but not triple-negative breast cancer. Associations for in situ tumors were similar to luminal A-like.CONCLUSION: This large and comprehensive study demonstrates a distinct reproductive risk factor profile for triple-negative breast cancer compared to other subtypes, with implications for the understanding of disease etiology and risk prediction.
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| 9. |
- Kapoor, Pooja Middha, et al.
(author)
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Combined associations of a polygenic risk score and classical risk factors with breast cancer risk
- 2021
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 113:3, s. 329-337
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Journal article (peer-reviewed)abstract
- We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72 284 cases and 80 354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression and a newly developed case-only method for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined by individual risk factors. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS313 and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS313 and family history) and, on average, 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk of breast cancer.
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| 10. |
- Shu, Xiang, et al.
(author)
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Associations of obesity and circulating insulin and glucose with breast cancer risk : a Mendelian randomization analysis
- 2019
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In: International Journal of Epidemiology. - : OXFORD UNIV PRESS. - 0300-5771 .- 1464-3685. ; 48:3, s. 795-806
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Journal article (peer-reviewed)abstract
- Background: In addition to the established association between general obesity and breast cancer risk, central obesity and circulating fasting insulin and glucose have been linked to the development of this common malignancy. Findings from previous studies, however, have been inconsistent, and the nature of the associations is unclear. Methods: We conducted Mendelian randomization analyses to evaluate the association of breast cancer risk, using genetic instruments, with fasting insulin, fasting glucose, 2-h glucose, body mass index (BMI) and BMI-adjusted waist-hip-ratio (WHRadj BMI). We first confirmed the association of these instruments with type 2 diabetes risk in a large diabetes genome-wide association study consortium. We then investigated their associations with breast cancer risk using individual-level data obtained from 98 842 cases and 83 464 controls of European descent in the Breast Cancer Association Consortium. Results: All sets of instruments were associated with risk of type 2 diabetes. Associations with breast cancer risk were found for genetically predicted fasting insulin [odds ratio (OR) = 1.71 per standard deviation (SD) increase, 95% confidence interval (CI) = 1.26-2.31, p = 5.09 x 10(-4)], 2-h glucose (OR = 1.80 per SD increase, 95% CI = 1.3 0-2.49, p = 4.02 x 10(-4)), BMI (OR = 0.70 per 5-unit increase, 95% CI = 0.65-0.76, p = 5.05 x 10(-19)) and WHRadj BMI (OR = 0.85, 95% CI = 0.79-0.91, p = 9.22 x 10(-6)). Stratified analyses showed that genetically predicted fasting insulin was more closely related to risk of estrogen-receptor [ER]-positive cancer, whereas the associations with instruments of 2h glucose, BMI and WHRadj BMI were consistent regardless of age, menopausal status, estrogen receptor status and family history of breast cancer. Conclusions: We confirmed the previously reported inverse association of genetically predicted BMI with breast cancer risk, and showed a positive association of genetically predicted fasting insulin and 2-h glucose and an inverse association of WHRadj BMI with breast cancer risk. Our study suggests that genetically determined obesity and glucose/insulin-related traits have an important role in the aetiology of breast cancer.
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