Obesity and adulthood weight gain increase the risk of developing breast cancer after menopause. Prior to menopause however, obesity is protective. Candidate genes that increase the likelihood of obesity may share etiologic pathways with development of breast cancer. We studied the PPARgamma2 (Peroxisome-proliferator-activated receptor (gamma)2 gene, a candidate gene for obesity, among population controls who participated in a multiethnic case-control study of breast cancer conducted in the San Francisco Bay Area.

The study population consisted of 296 premenopausal women and 534 postmenopausal women with measurements of genotype and body composition (weight, height, waist and hip circumference). We found no overall association between body composition measurements and PPARgamma2 among all controls combined. Associations became apparent however when we stratified the analyses according to menopausal status and race/ethnicity.

Among Black women, we observed associations of the PPAR-gamma variant Pro12Ala with waist circumference (p = 0.05) and marginally (p = 0.06) with waist-to-hip ratio among premenopausal women that were not observed among postmenopausal women. We also observed associations among Latina premenopausal women: Pro12Ala variant was associated with body-mass index (p = 0.04) and marginally with waist circumference (p = 0.06). We did not see associations among White premenopausal and postmenopausal women, nor did we observe associations among Latina postmenopausal women.

PPARgamma2, originating from a subfamily of nuclear hormone receptors, is a transcription factor that controls the expression of a large array of genes involved in adipocyte differentiation, lipid storage and insulin sensitization. PPARgamma2 variant Pro12Ala has primarily been studied in the context of diabetes and cardiovascular disease and rarely evaluated in relationship to cancer. The present study suggests that Pro12Ala may affect body composition among younger Latina and Black women which could be important for developing breast cancer.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA