Polymorphisms in adiposity-related genes are associated with age at menarche and menopause in breast cancer patients and healthy women

Is there any effect of genetic polymorphisms in adiposity-related genes on the timing of menarche and menopause and the total duration of menstruation among Korean women? Our results suggest that the adiposity-related genes LEP, LEPR and PPAR may play a role in the onset and cessation of menstruation, and the total duration of menstruation. Previous candidate-gene approaches have mainly presented the results for genes related to the estrogen metabolism pathway. Most genes of interest that participate in steroid-hormone metabolism, such as estrogen receptor and estrogen receptor , have been associated with age at menarche and menopause. This study shows the possibility that adiposity-related genes also influence the duration of menstruation. We recruited 400 breast cancer patients and 452 healthy participants from a casecontrol study at the Center for Breast Cancer, National Cancer Center in Korea. Ten single nucleotide polymorphisms (SNPs) in the leptin (LEP), leptin receptor (LEPR) and peroxisome proliferator-activated receptor gamma (PPAR) genes were investigated to evaluate their possible effects on menstruation. Associations between SNPs and age at menarche, age at menopause and duration of menstruation were evaluated. Four SNPs (rs2167270 of LEP, rs7602 of LEPR and rs4684846 and rs3856806 of PPAR) were associated with late menarche (epsilon 17-year-old). Four SNPs (rs2167270 of LEP and rs1801282, rs2120825, and rs3856806 of PPAR) were associated with early menopause (40-year-old) among post-menopausal women. In logistic regression models with covariate adjustment, women with the GG genotype of rs7602 (LEPR) had a higher risk for late menarche [odds ratio (OR) 1.83, 95 confidence interval (CI) 1.013.31] compared with their counterparts carrying the GA or AA genotypes. In addition, the GG genotype of rs2167270 (LEP) was inversely associated with a duration of menstruation of 30 years (OR 0.59, 95 CI 0.311.00) compared with the GA or AA genotypes. We obtained information on the age at menarche and menopause from self-administered questionnaires, and some participants might have had difficulty in remembering their age at menarche and menopause. However, this is a non-differential misclassification and should not appreciably affect the interpretation of the results of this study. This study was supported by a grant from the National Cancer Center Korea (0610550-2 and 0911220).