PS2-41: The FTO Gene, Its Variants and Post-menopausal Breast Cancer

Abstract

Background Adiposity is a well-accepted risk factor for post-menopausal breast cancer (PMBC). SNPs of the FTO gene, located on chromosome 16q12.2, have been associated with adiposity by lowering the activity of the enzyme lipase. This gene also encodes for a protein involved in DNA damage repair pathway. The current epidemiologic paradigm associates the risk of PMBC with increased aromatization of androstenedione to estradial in peripheral adipose tissue and increased serum levels of insulin-like growth-factors. The increased systemic inflammation because of adiposity motivates the inquiries for other plausible biochemical mechanism. We are conducting a pilot nested case-controls study to investigate the association between 3 SNPs of FTO gene with the risk of PMBC, adjusted for the major risk factors. Presently data are available from 50 cases and 202 controls from the cohort of MyCode Biobanking Project at Geisinger Health System. Methods We genotyped the 3 SNPs (rs1861868, rs1477196 and rs9939609) of the gene. Generalized linear model was used to evaluate the association between these 3 SNPs. We also conducted analyses of hyplotypes for 2-SNPs and 3-SNPs association, respectively; odds ratios (OR) and 95% confidence intervals (CI) were calculated to estimate the association between haplotypes and PMBC, and between the genotypes of each SNPs (as an ordinal variable) and PMBC applying unconditional logistic regression modeling approach, while controlling for BMI, age, parity status (=3 or <3) and family history for breast cancer. Results Our analyses suggest that 2 of the SNPs (rs1861868 and rs1477196) most likely form a haplotype (P= 0.002) that is exclusive of the third SNP (rs9939609, P>0.3). None of these SNPs or hyplotypes was associated with BMI (p>0.4), diabetes and metabolic syndrome (P>0.15). Results from the multivariate logistic model suggested a trend toward a potential association (OR=1.68, CI=0.67-4.18, P=0.09) between the (rs1861868) SNP and PMBC. Conclusion Our pilot study attempts to evaluate the association between SNPs of the of FTO gene with PMBC, independent of BMI or other risk factors for PMBC. One SNP was found to be likely associated with PMBC, but the present small sample size eclipses the power of identifying a definite association.