Assessing The Effect Of The Fto (rs9939609) Gene On Weight Loss Among Breast Cancer Survivors Enrolled In The Lifestyle, Exercise, And Nutrition (lean) Study

Hien Thai Nguyen

This thesis is restricted to Yale network users only. It will be made publicly available on 08/28/2020


Abstract: Background: A single nucleotide polymorphism (SNP) of the Fat, Mass, and Obesity associated (FTO) gene, rs9939609, is significantly associated with obesity and individual variability in weight loss achieved by diet/lifestyle interventions. However, study results on the effect of the FTO gene on weight loss remains inconsistent. This study aims to examine the moderating effects of the FTO SNP rs9939609 on weight loss achieved by a lifestyle intervention in breast cancer survivors. Methods: Breast cancer survivors with a body mass index (BMI) > 25 kg/m2 were randomized to the LEAN 6-month intervention, which included eleven 30-min counseling sessions focused on reducing caloric intake, increasing physical activity and behavioral therapy or to a usual care group. Fasting blood was collected at baseline and 6 months, with genotyping of the SNP rs9939609 using the Taqman® SNP genotyping assay. The main effects of genotype and weight loss intervention on outcome changes were analyzed using general linear models, with adjustment for age at baseline. Results: There were 30.4% of individuals with the wild-type TT genotype, 50% with AT- genotype, and 19.7% with AA-genotype. No significant interaction between genotype and randomization group observed for changes in weight, BMI, and total fat% (p = 0.945, 0.932, and 0.176, respectively). Weight loss was higher in women in the intervention group, as compared to the usual care group (-4.8 vs -0.6 kg, p < 0.001) and across all genotypes (p < 0.05). Weight changes did not significantly differ among those with AA/AT or TT genotypes (p > 0.05). Conclusions: Genetic variation of the FTO gene rs9939609 did not modify the effect of the weight-loss intervention on changes in body weight. Women who are genetically predisposed to obesity and recently diagnosed with breast cancer benefit from lifestyle changes similarly to women who are not genetically predisposed to obesity. Our findings may help guide the incorporation of lifestyle interventions and weight loss counseling into breast cancer survivorship care.