Abstract B61: Maternal and intrauterine hormone-related exposures and daughter's age at menarche in a multiethnic population in Hawaii

The aim of this study is to further elucidate the mother-daughter hormonal relationship and its effects on the daughter's breast cancer risk, through the association with earlier age at menarche. Healthy girls residing on the island of Oahu, between the ages of 9–18 years and of white, Asian, or Polynesian ethnicity, or a mix thereof, were recruited from Kaiser Permanente Hawaii. Anthropometric measures were taken of each participant at a clinic visit, and together with one of her parents, each participant completed a family background questionnaire that requested information on infant characteristics, mother's pregnancy, family history of breast cancer, and the age at menarche for both mother and daughter. Cox proportional hazards regression, with age as the time metric, was used to determine the association between the maternal and intrauterine exposures and age at menarche. Tests for interactions between ethnicity and mother's age at menarche was performed by including as variables in the model product terms of each ethnicity dummy variable by the continuous variable of mother's age at menarche, along with each of the individual main-effect variables. The ethnic make-up of the 438 participants was categorized as follows: 31% mixed race (part-Polynesian plus Asian and/or white), 30% mixed race (white and Asian only), 23% all Asian, and 16% all white. Being all Asian, as compared to being all white, was associated with a greater risk of an earlier age at menarche, adjusted for age and waist circumference (HR = 1.87, 95% CI: 1.29–2.71). Each year older the mother was when she began menstruating was associated with a 21% reduced risk of a relatively earlier age at menarche for the daughter, adjusted for age, race/ethnicity, and waist circumference (95% CI: 0.73–0.86). When stratifying by race/ethnicity, mother's age at menarche (as a continuous variable) was significantly associated with age at menarche for girls of all white (HR=0.53, 95% CI: 0.39–0.72), mixed white/Asian (HR=0.77, 95% CI: 0.64–0.92), and all Asian race (HR=0.79, 0.70–0.90), adjusting for age and waist circumference, but not for girls of mixed, part-Polynesian race, resulting in a significant difference between the association for mixed, part-Polynesian girls and possibly for fully Asian girls, as compared to fully white girls (p's for interaction = 0.01 and 0.06, respectively). Being of less than 36 gestational weeks at birth was associated with a doubling of risk (95% CI: 1.05–3.86) for an earlier age at menarche, but being of greater than 41 weeks was not associated with risk. There was the suggestion that having a mother with a history of breast cancer was associated with an increase in risk of an earlier age at menarche (HR=2.18, 95% CI: 0.95–4.98). Having a second degree family history of breast cancer, a low or high birth weight, or a mother who experienced severe pregnancy-induced nausea was not associated with age at menarche. These findings give strong support to the hypothesis that maternal and intrauterine hormone-related exposures affect a girl's risk for earlier age at menarche. Knowledge of the risk factors for early age at menarche among various populations, especially when able to examine their direct relationship with breast cancer risk, will help in identifying women at increased risk and, hopefully, lead to earlier detection, and greater survival, through better screening.