No evidence of a role for PPARγ Pro¹²Ala polymorphism in endometrial cancer susceptibility

Endogenous oestrogens play a crucial role in endometrial cancer pathogenesis, with most endometrial cancer risk factors causing an increase in oestrogens. Adipose tissue, where androgens are converted to oestrogens by the enzyme aromatase, is an important source of endogenous oestrogen production in the postmenopausal woman. The peroxisome proliterator-activated receptor-gamma (PPARγ), a key transcriptional regulator of adipogenesis, may also play a role in the regulation of aromatase expression in adipose tissue. We hypothesized that the functional PPARγ Pro¹²Ala polymorphism may alter aromatase expression, ultimately affecting endometrial cancer susceptibility. We genotyped the PPARγ Pro¹²Ala polymorphism in a study of invasive endometrial cancer cases (n = 222) and matched controls (n = 666) nested within the Nurses' Health Study Cohort. We found little or no evidence of an association between the Ala allele of the PPARγ codon 12 polymorphism and endometrial cancer risk (adjusted odds ratio = 1.18, 95% confidence interval = 0.80-1.76). Furthermore, we found no association with the PPARγ Pro¹²Ala polymorphism and the ratio of oestrone to androstenedione or oestradiol to testosterone plasma hormone levels, measures of aromatase activity. Consistent with previous findings for breast cancer, these results suggest that the PPARγ Pro¹²Ala polymorphism does not play a major role in mediating circulating oestrogen levels or endometrial cancer susceptibility.