PPARG and colorectal cancer: Carriers of the variant allele of PPARG Pro12Ala were at increased risk of alcohol-related colorectal cancer (IRR 1.22 pr.10 g alcohol/day, 95% CI: 1.07–1.39), whereas homozygous wildtype Pro-allele carriers were not.32 The underlying mechanism of action was recently elucidated.33 Hormone replacement therapy is a risk factor for breast cancer, but seems to be associated with lowered risk of colorectal cancer.34 PPARγ is a negative regulator of the blood level of female sex hormones (via aromatase activity).