Interactions Between Adiponectin-Pathway Polymorphisms and Obesity on Postmenopausal Breast Cancer Risk Among African American Women: The WHI SHARe Study

BACKGROUND: A decreased level of serum adiponectin is associated with obesity and an increased risk of breast cancer among postmenopausal women. Yet, the interplay between genetic variants associated with adiponectin phenotype, obesity, and breast cancer risk is unclear in African American (AA) women. METHODS: We examined 32 single-nucleotide polymorphisms (SNPs) previously identified in genome-wide association and replication studies of serum adiponectin levels using data from 7,991 AA postmenopausal women in the Women’s Health Initiative SNP Health Association Resource. RESULTS: Stratifying by obesity status, we identified 18 adiponectin-related SNPs that were associated with breast cancer risk. Among women with BMI ≥ 30 kg/m(2), the minor TT genotype of FER rs10447248 had an elevated breast cancer risk. Interaction was observed between obesity and the CT genotype of ADIPOQ rs6773957 on the additive scale for breast cancer risk (relative excess risk due to interaction, 0.62; 95% CI, 0.32–0.92). The joint effect of BMI ≥ 30 kg/m(2) and the TC genotype of OR8S1 rs11168618 was larger than the sum of the independent effects on breast cancer risk. CONCLUSIONS: We demonstrated that obesity plays a significant role as an effect modifier in an increased effect of the SNPs on breast cancer risk using one of the most extensive data on postmenopausal AA women. IMPACT: The results suggest the potential use of adiponectin genetic variants as obesity-associated biomarkers for informing AA women who are at greater risk for breast cancer and also for promoting behavioral interventions, such as weight control, to those with risk genotypes.