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



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.


151 breast cancer survivors with a body mass index ≥ 25 kg/m2 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.


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).


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)

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Fig. 1

Data availability

Although data sharing will not be available in a public database, deidentified study data and study protocol will be shared upon reasonable request up until December 31, 2025, by contacting the corresponding author.

Code availability

The study statistical analysis plan will be shared upon reasonable request up until December 31, 2025, by contacting the corresponding author.


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We are thankful to the LEAN participants for their time and dedication with the LEAN study.


Supported by American Institute for Cancer Research and in part by a grant from the Breast Cancer Research Foundation. Also supported in part by the Yale Cancer Center Support Grant P30 CA016359 and the Clinical and Translational Science Award Grant Number UL1 TR000142 from the National Center for Advancing Translational Science, a component of the National Institutes of Health.

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Conception and design: TN, YDS, and MLI. Financial Support: MLI. Provision of study materials or patients: MH, TS, MLI. Collection and assembly of data: TN, MH, BC, LL, and MLI. Data analysis and interpretations: All authors. Manuscript writing: All authors. Final approval of manuscript: All authors.

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Correspondence to ThaiHien Nguyen.

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Nguyen, T., Irwin, M.L., Dewan, A.T. et al. Examining the effect of obesity-associated gene variants on breast cancer survivors in a randomized weight loss intervention. Breast Cancer Res Treat 187, 487–497 (2021). https://doi.org/10.1007/s10549-021-06151-5

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  • Obesity
  • Breast Cancer
  • Genetics
  • Nutrition
  • Exercise
  • Weight loss