| Epidemiological studies have shown that delayed age at natural menopause (age 55+) confers a roughly 2-fold increased risk of breast cancer, compared to women with early menopause (< 45). Identification of factors that determine the timing of natural menopause should provide insight into the complex etiology of breast cancer. The epidemiological literature on the determinants of age at natural menopause has verified few determinants of age at natural menopause. This literature, in combination with results from a cross-sectional analysis of data from the Hawaii and Los Angeles Multiethnic Cohort Study (MEC) showing that age at natural menopause differs in a statistically significant manner across racial/ethnic groups even after adjustment for covariates, provides support for the hypothesis that age at natural menopause is driven by a combination of reproductive, lifestyle and genetic factors. We selected three genes in two candidate pathways for investigation using a haplotype-based approach to test for possible association with age at natural menopause and identified several associations which we intend to follow up in future, larger studies. We also submitted a postdoctoral fellowship grant application entitled "Reproductive, lifestyle and genetic determinants of the age at natural menopause: The Multiethnic Cohort". We proposed to perform a study of the reproductive and lifestyle correlates of age at natural menopause in the California Teachers Study Cohort. We also proposed to extend our genetic analysis in the MEC by applying the haplotype-based approach to genes in a novel candidate pathway, the inhibin/activin pathway. These investigations have provided insight into this complex phenotype, and illuminated the need for further study. |
