Variation in genes related to obesity, weight and weight change and risk of contralateral breast cancer in the WECARE Study population.
ABSTRACT BACKGROUND: Body mass index (BMI), a known breast cancer risk factor, could influence breast risk through mechanistic pathways related to sex hormones, insulin resistance, chronic inflammation and altered levels of adipose derived hormones. Results from studies of the relationship between BMI and second primary breast cancer have been mixed. To explore the relationship between BMI and asynchronous contralateral breast cancer (CBC), we examined whether variants in genes related to obesity, weight and weight change are associated with CBC risk. METHODS: Variants in twenty genes (182 single nucleotide polymorphisms) involved in adipose tissue metabolism, energy balance, insulin resistance and inflammation, as well as those identified through genome-wide association studies of BMI and type II diabetes were evaluated. We examined the association between variants in these genes and the risk of CBC among Caucasian participants (643 cases with CBC and 1,271 controls with unilateral breast cancer) in the population-based Women's Environmental Cancer and Radiation Epidemiology (WECARE) Study using conditional logistic regression. RESULTS: After adjustment for multiple comparisons, no statistically significant associations between any variant and CBC risk were seen. Stratification by menopausal or estrogen receptor status did not alter these findings. CONCLUSIONS: Among women with early onset disease who survive a first breast cancer diagnosis there was no association between variation in obesity-related genes and risk of CBC. Impact:Genetic variants in genes related to obesity are not likely to strongly influence subsequent risk of developing a second primary breast cancer.
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ABSTRACT: The prevalence of risk factors contributing to metabolic syndrome (MetS) is increasing, and numerous components of MetS are associated with increased primary breast cancer (BC) risk. However, less is known about the relationship of MetS to BC outcomes. The aim of this study was to evaluate whether MetS, characterized by increased weight, hypertension, low HDL-cholesterol, high triglycerides, and diabetes or impaired glucose tolerance, is associated with risk of second breast cancer events (SBCE) and BC-specific mortality. Retrospective cohort study of women diagnosed with incident early-stage (I-II) BC between 1990 and 2008, enrolled in an integrated health plan. Outcomes of interest were SBCE, defined as recurrence or second primary BC, and BC-specific mortality. We used multivariable Cox proportional hazards models to estimate adjusted hazard ratios (HR) and 95 % confidence intervals (CI) for time-varying exposure to MetS components while accounting for potential confounders and competing risks. Among 4,216 women in the cohort, 26 % had >/=3 MetS components and 13 % developed SBCE during median follow-up of 6.3 years. Compared to women with no MetS components, presence of MetS (>/=3 components) was associated with increased risk of SBCE (HR = 1.50, 95 % CI 1.08-2.07) and BC-specific mortality (HR = 1.65, 95 % CI 1.02-2.69). Of the individual components, only increased weight was associated with increased risk of SBCE (HR = 1.26, 95 % CI 1.06-1.49). MetS is associated with modestly increased risk of SBCE and BC-specific mortality. Given the growing population of BC survivors, further research in larger and more diverse populations is warranted.Breast Cancer Research and Treatment 10/2014; · 4.20 Impact Factor