Genetic polymorphisms in DNA repair and oxidative stress pathsways may modify the association between body size and postmenopausal breast cancer
Menée aux Etats-Unis à partir de données de 990 cas et 970 témoins, cette étude analyse l'impact de 29 polymorphismes des gènes associés à la réparation de l'ADN et impliqués dans la réponse à un stress oxydant sur la modification de l'association entre l'obésité et le risque de cancer du sein après la ménopause
Purpose : Obesity is associated with increased bioavailability of estrogen, hyperinsulemia and chronic inflammation, all of which may promote tumor growth. Given DNA repair and oxidative stress pathways may work together with these mechanisms to influence carcinogenesis, we hypothesized that genetic variation in these pathways may modify the obesity-postmenopausal breast cancer association. Methods : Resources from a population-based case-control study (990 cases/970 controls) were used to construct logistic regression models. Body mass index (BMI, weight kg/height m2) was assessed 1-year prior to reference date. We characterized interactions between BMI and 29 genetic polymorphisms in oxidative stress and DNA repair pathways. Results : Age-adjusted odds ratios (95% confidence intervals) for postmenopausal breast cancer were 1.24 (1.00-1.52) and 1.35 (1.09-1.71) for 25>BMI<30 and BMI≥30, respectively. We observed multiplicative interactions (p≤0.05) for eight gene polymorphisms in DNA repair and oxidative stress pathways. For example, among MPO variant allele carriers, obesity was associated with a two-fold increased risk of postmenopausal breast cancer [2.13 (1.35-3.36)]; however in wild-type homozygotes, the relationship was less pronounced [1.33 (0.93-1.89)]. Our findings were no longer significant after Bonferroni correction. Conclusions : Obesity may be particularly deleterious for postmenopausal breast cancer development in the presence of biologically plausible DNA repair or oxidative stress genotypes.