Alcohol is a risk factor for postmenopausal breast cancer. One of several proposed mechanisms is that alcohol-related breast cancer is caused by increased sex hormone levels. PPAR¿ inhibits aromatase transcription in breast adipocytes. We reproduced previously found allele-specific effects of the wildtype Pro-allele of PPARG Pro(12)Ala in alcohol related breast cancer. In transiently transfected cells, transcriptional activation by PPAR¿ and the PPAR¿-PGC-1a complex was inhibited by ethanol. PPAR¿ 12Ala-mediated transcription activation was not enhanced by PGC-1a, resulting in allele-specific transcription activation by the PPAR¿ 12Pro-PGC-1a complex. Our results suggest that PPAR¿ and PGC-1a activity is an important determinant of alcohol related breast cancer.