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Prospective evaluation of body size and breast cancer risk among BRCA1 and BRCA2 mutation carriers.

ABSTRACT: BACKGROUND:Although evidence suggests that larger body size in early life confers lifelong protection from developing breast cancer, few studies have investigated the relationship between body size and breast cancer risk among BRCA mutation carriers. Therefore, we conducted a prospective evaluation of body size and the risk of breast cancer among BRCA mutation carriers. METHODS:Current height and body mass index (BMI) at age 18 were determined from baseline questionnaires. Current BMI and weight change since age 18 were calculated from updated biennial follow-up questionnaires. Cox proportional hazards models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI). RESULTS:Among 3734 BRCA mutation carriers, there were 338 incident breast cancers over a mean follow-up of 5.5?years. There was no association between height, current BMI or weight change and breast cancer risk. Women with BMI at age 18??22.1?kg/m2 had a decreased risk of developing post-menopausal breast cancer compared with women with a BMI at age 18 between 18.8 and 20.3?kg/m2 (HR 0.49; 95% CI 0.30-0.82; P?=?0.006). BMI at age 18 was not associated with risk of pre-menopausal breast cancer. CONCLUSIONS:There was no observed association between height, current BMI and weight change and risk of breast cancer. The inverse relationship between greater BMI at age 18 and post-menopausal breast cancer further supports a role of early rather than current or adulthood exposures for BRCA-associated breast cancer development. Future studies with longer follow-up and additional measures of adiposity are necessary to confirm these findings.

SUBMITTER: Kim SJ

PROVIDER: S-EPMC6005062 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Prospective evaluation of body size and breast cancer risk among BRCA1 and BRCA2 mutation carriers.

Kim Shana J SJ Huzarski Tomasz T Gronwald Jacek J Singer Christian F CF Møller Pål P Lynch Henry T HT Armel Susan S Karlan Beth Y BY Foulkes William D WD Neuhausen Susan L SL Senter Leigha L Eisen Andrea A Eng Charis C Panchal Seema S Pal Tuya T Olopade Olufunmilayo O Zakalik Dana D Lubinski Jan J Narod Steven A SA Kotsopoulos Joanne J

International journal of epidemiology 20180601 3

<h4>Background</h4>Although evidence suggests that larger body size in early life confers lifelong protection from developing breast cancer, few studies have investigated the relationship between body size and breast cancer risk among BRCA mutation carriers. Therefore, we conducted a prospective evaluation of body size and the risk of breast cancer among BRCA mutation carriers.<h4>Methods</h4>Current height and body mass index (BMI) at age 18 were determined from baseline questionnaires. Current ...[more]

PMID: 29547931

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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

Prospective evaluation of body size and breast cancer risk among BRCA1 and BRCA2 mutation carriers.

Publications

Prospective evaluation of body size and breast cancer risk among BRCA1 and BRCA2 mutation carriers.

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