Obesity is a major health problem in the United States associated with an increased risk of postmenopausal breast cancer, endometrial and colon cancers as well as diabetes, hypertension, and coronary heart disease. Based on the National Health and Nutrition Examination Survey (NHANES) III, 33% of adults and 22% of children in America are overweight, with a two-fold higher prevalence in African-American than Caucasian women, after adjustment for socioeconomic status (1). Over the past 30 years, the most dramatic increases in the proportion overweight has occurred in African-American girls, who have experienced age-specific increases of 80-150% compared to an increase of 35% in Caucasian girls (2). Over a similar window of time, the average age at onset of menarche in African-American girls has dropped from 12.5 to 12.0 years in contrast with a slower decline from 12.8 to 12.5 years in Caucasian girls (3-4). Not only are African-American girls experiencing an earlier age at menarche, a recognized risk factor for breast cancer, but the median age at onset of puberty occurs significantly earlier in African-American girls than in Caucasian and Mexican-American girls in NHANES III. African-American women of reproductive age have higher cyclic fluctuations of estradiol and progesterone and higher percentage of ovulatory menstrual cycles than their Hispanic and non-Hispanic white peers (Haimon C, 2002), thereby identifying African-American women as the group with the potential to have the longest life cycle and highest circulating levels of endogenous hormone exposures than other ethnic group in the United States (6). Indeed, African American women have the potential for a long life cycle of endogenous hormone exposures and a concomitantly high prevalence of overweight/obesity, which sets the stage for this ethnic group to be at high risk of the leading adult cancers. The interaction of genetic and lifestyle factors may influence the rate of linear growth, body mass, and maturational development from early life through adolescence. A high activity genetic variant of cytochrome P 450 3A41B, which predominates in testosterone catabolism, has a higher frequency in African-Americans than Hispanic and non-Hispanic whites and has been strongly associated with earlier age at onset of puberty in a small study. Thus a specific subset of African-American girls may have a genotype that confers increased risk of early puberty, a potential risk factor for early menarche. Moreover, several recent reports describe higher mean energy expenditure in Caucasian than African American girls, but findings are not consistent by pubertal status (12-14). In the proposed study, we seek to investigate the association between environmental, hormonal and genetic factors influencing ethnic-group differences in pubertal stage in African American and Caucasian girls and pilot test the utility of CYP3A4 as a marker of early puberty. This research is designed as a cross-sectional study of (N= 400) healthy, non-diabetic African-American and Caucasian girls of pre-pubertal and pubertal years (aged 7-9.9 y) and their mothers.
