Examining the effect of obesity-associated gene variants on breast cancer survivors in a randomized weight loss intervention

Purpose Our study examined whether common variants of obesity-associated genes FTO , MC4R , BDNF , and CREB1 moderated the effects of a lifestyle intervention on weight change among breast cancer survivors. Methods 151 breast cancer survivors with a body mass index ≥ 25 kg/m 2 were randomly assigned to a 6-month weight loss intervention or usual care group. Genotyping of FTO rs9939609, MC4R rs6567160, BDNF rs11030104, CREB1 rs17203016 was performed. Linear mixed models were used including the main effects of genotype (assuming a dominant genetic model), treatment arm on weight and percent body fat changes, and genotype by treatment interaction variable. All statistical tests were evaluated against a Bonferroni-corrected alpha of 0.0125. Results Women in the intervention group achieved significantly greater weight loss than the usual care group (5.9% vs 0.4%, p < 0.001), regardless of genotype. Changes in weight and percent body fat did not differ significantly between carriers of the FTO rs9939609, MC4R rs6567160, BDNF rs11030104, and CREB1 rs17203016 risk alleles compared to non-carriers (p-interaction > 0.0125 for each single-nucleotide polymorphisms). Conclusions Women who are genetically predisposed to obesity and recently diagnosed with breast cancer may achieve significant and clinically meaningful weight loss through healthy eating and exercise. Clinical Trial Registration: NCT02863887 (Date of Registration: August 11, 2016); NCT02110641 (Date of Registration: April 10, 2014)