Association between FTO rs9939609 genotype and breast cancer risk after bariatric surgery in the Swedish Obese Subjects study

Abstract The FTO rs9939609 SNP has been linked to higher BMI, insulin resistance, and breast cancer risk. Weight loss by bariatric surgery lowers breast cancer risk, particularly in women with baseline hyperinsulinemia, but it is unclear whether this effect varies by FTO genotype. In the Swedish Obese Subjects (SOS) study, 2596 women with severe obesity were followed for a median of 23.9 years to examine breast cancer incidence after bariatric surgery compared with usual care. Genotyping for rs9939609 was performed, and breast cancer events were identified via the Swedish National Cancer Registry. Among 135 breast cancer cases (77 in the control group and 58 in the surgery group), surgery was associated with a lower breast cancer incidence in carriers of the risk allele (TA/AA) (adjusted HR = 0.53 0.34–0.83, P = 0.005), but not in non-carriers (TT) (adjusted HR = 1.19 0.65–2.15, P = 0.573; P for treatment-genotype interaction = 0.031). These findings suggest that the FTO rs9939609 genotype may modify the association between bariatric surgery and breast cancer incidence. Trial registration: ClinicalTrials.gov, identifier: NCT01479452.