The role of genome-wide association study confirmed obesity-related single nucleotide polymorphisms in the etiology of postmenopausal breast cancer

Thursday, October 11, 2012 — Poster Session III
10:00 a.m. – Noon	Natcher Conference Center, Building 45	NCI	EPID-9

Authors

• SM George
• D Albanes
• SC Moore
• MH Gail
• MM Gaudet
• LA Brinton
• M Garcia-Closas
• S Berndt

Abstract

Examination of how genetic risk factors for the obesity phenotype are related to breast cancer may help identify the biological underpinnings of the obesity-breast cancer relation. In the Polish Breast Cancer Study, we genotyped eight single nucleotide polymorphisms (SNPs) in FTO, GNPDA2, MC4R, TMEM18, KCTD15, NEGR1, ETV5, and BDNF that were significantly related to body-mass index (BMI) in recent genome-wide association studies. Using unconditional logistic regression, we calculated odds ratios (OR) and 95% confidence intervals (CI) per effect allele copy to estimate the association between each SNP and breast cancer risk, controlling for age and study site. We also investigated heterogeneity by obesity status, molecular subtype (luminal A, luminal B, HER-2 expressing, basal-like, normal-like), and tumor size. Among 1146 invasive postmenopausal breast cancer cases and 1471 frequency-matched controls, the obesity-associated allele (C) near MC4R (Rs17782313) was inversely related to breast cancer (OR: 0.84, 95% CI: 0.73, 0.96, p=0.01). The other seven BMI-associated variants were not related to breast cancer. The relationship between MC4R and breast cancer was similar after adjustment for obesity and did not significantly differ by obesity status, molecular subtype, or tumor size. Genomic variation near MC4R may affect breast cancer risk through mechanisms independent from obesity.

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