Dataset Information

Lifestyle Risk Factors for Breast Cancer in BRCA1/2-Mutation Carriers Around Childbearing Age.

ABSTRACT: BRCA1/2-mutation carriers are at high risk of breast cancer (BC) and ovarian cancer. Physical inactivity, overweight (body mass index ?25, BMI), smoking, and alcohol consumption are jointly responsible for about 1 in 4 postmenopausal BC cases in the general population. Limited evidence suggests physical activity also increases BC risk in BRCA1/2-mutation carriers. Women who have children often reduce physical activity and have weight gain, which increases BC risk. We assessed aforementioned lifestyle factors in a cohort of 268 BRCA1/2-mutation carriers around childbearing age (born between 1968 and 1983, median age 33 years, range 21-44). Furthermore, we evaluated the effect of having children on physical inactivity and overweight. Carriers were asked about lifestyle 4-6 weeks after genetic diagnosis at the Familial Cancer Clinic Nijmegen. Physical inactivity was defined as sports activity fewer than once a week. Carriers were categorized according to the age of their youngest child (no children, age 0-3 years and ?4 years). In total, 48% of carriers were physically inactive, 41% were overweight, 27% smoked, and 70% consumed alcohol (3% ?8 beverages/week). Physical inactivity was 4-5 times more likely in carriers with children. Overweight was not associated with having children. Carriers with children are a subgroup that may specifically benefit from lifestyle support to reduce BC risk.

SUBMITTER: van Erkelens A

PROVIDER: S-EPMC5502067 | biostudies-other | 2017 Aug

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Lifestyle Risk Factors for Breast Cancer in BRCA1/2-Mutation Carriers Around Childbearing Age.

van Erkelens A A Derks L L Sie A S AS Egbers L L Woldringh G G Prins J B JB Manders P P Hoogerbrugge N N

Journal of genetic counseling 20161213 4

BRCA1/2-mutation carriers are at high risk of breast cancer (BC) and ovarian cancer. Physical inactivity, overweight (body mass index ≥25, BMI), smoking, and alcohol consumption are jointly responsible for about 1 in 4 postmenopausal BC cases in the general population. Limited evidence suggests physical activity also increases BC risk in BRCA1/2-mutation carriers. Women who have children often reduce physical activity and have weight gain, which increases BC risk. We assessed aforementioned life ...[more]

PMID: 27966054

Similar Datasets

Project description:Importance:Prophylactic bilateral salpingo-oophorectomy is recommended for BRCA1 mutation carriers to prevent ovarian cancer. Whether or not hormone replacement therapy (HRT) initiated after oophorectomy is associated with an increased risk of breast cancer has not been evaluated in a prospective study. Objective:To determine the association between HRT use and BRCA1-associated breast cancer. Design, Setting, and Participants:A prospective, longitudinal cohort study of BRCA1 and BRCA2 mutation carriers from 80 participating centers in 17 countries was conducted between 1995 and 2017 with a mean follow-up of 7.6 years. Participants had sought genetic testing for a BRCA1 or BRCA2 mutation because of a personal or family history of breast and/or ovarian cancer. Carriers of BRCA1 mutation with no personal medical history of cancer who underwent bilateral oophorectomy following enrollment were eligible for the cohort study. Exposures:A follow-up questionnaire was administered every 2 years to obtain detailed information on HRT use. A left-truncated Cox proportional hazard analysis was used to estimate the hazard ratios (HRs) and 95% CIs associated with the initiation of HRT use postoophorectomy. Main Outcomes and Measures:Incident breast cancer. Results:A total of 872 BRCA1 mutation carriers with a mean postoophorectomy follow-up period of 7.6 years (range, 0.4-22.1) were included in this study. Mean (SD) age of participants was 43.4 (8.5) years. Among these, 92 (10.6%) incident breast cancers were diagnosed. Overall, HRT use after oophorectomy was not associated with an increased risk of breast cancer. The HR was 0.97 (95% CI, 0.62-1.52; P = .89) for ever use of any type of HRT vs no use; however, the effects of estrogen alone and combination hormonal therapy were different. After 10 years of follow-up, the cumulative incidence of breast cancer among women who used estrogen-alone HRT was 12% compared with 22% among women who used estrogen plus progesterone HRT (absolute difference, 10%; log rank P = .04). Conclusions and Relevance:These findings suggest that use of estrogen after oophorectomy does not increase the risk of breast cancer among women with a BRCA1 mutation and should reassure BRCA1 mutation carriers considering preventive surgery that HRT is safe. The possible adverse effect of progesterone-containing HRT warrants further study.

Project description:BackgroundGenome-wide association studies (GWAS) have identified 94 common single-nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk and 18 associated with ovarian cancer (OC) risk. Several of these are also associated with risk of BC or OC for women who carry a pathogenic mutation in the high-risk BC and OC genes BRCA1 or BRCA2. The combined effects of these variants on BC or OC risk for BRCA1 and BRCA2 mutation carriers have not yet been assessed while their clinical management could benefit from improved personalized risk estimates.MethodsWe constructed polygenic risk scores (PRS) using BC and OC susceptibility SNPs identified through population-based GWAS: for BC (overall, estrogen receptor [ER]-positive, and ER-negative) and for OC. Using data from 15 252 female BRCA1 and 8211 BRCA2 carriers, the association of each PRS with BC or OC risk was evaluated using a weighted cohort approach, with time to diagnosis as the outcome and estimation of the hazard ratios (HRs) per standard deviation increase in the PRS.ResultsThe PRS for ER-negative BC displayed the strongest association with BC risk in BRCA1 carriers (HR = 1.27, 95% confidence interval [CI] = 1.23 to 1.31, P = 8.2×10 -53 ). In BRCA2 carriers, the strongest association with BC risk was seen for the overall BC PRS (HR = 1.22, 95% CI = 1.17 to 1.28, P = 7.2×10 -20 ). The OC PRS was strongly associated with OC risk for both BRCA1 and BRCA2 carriers. These translate to differences in absolute risks (more than 10% in each case) between the top and bottom deciles of the PRS distribution; for example, the OC risk was 6% by age 80 years for BRCA2 carriers at the 10th percentile of the OC PRS compared with 19% risk for those at the 90th percentile of PRS.ConclusionsBC and OC PRS are predictive of cancer risk in BRCA1 and BRCA2 carriers. Incorporation of the PRS into risk prediction models has promise to better inform decisions on cancer risk management.

Dataset Information

Lifestyle Risk Factors for Breast Cancer in BRCA1/2-Mutation Carriers Around Childbearing Age.

Publications

Lifestyle Risk Factors for Breast Cancer in BRCA1/2-Mutation Carriers Around Childbearing Age.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets