Long-term and recent recreational physical activity and survival after breast cancer: the California Teachers Study.

INTRODUCTION: Long-term physical activity is associated with lower breast cancer risk. Little information exists on its association with subsequent survival. METHODS: California Teachers Study cohort members provided information in 1995-1996 on long-term (high school through age 54 years) and recent (past 3 years) participation in moderate and strenuous recreational physical activities. The 3,539 women diagnosed with invasive breast cancer after cohort entry and through December 31, 2004, were followed through December 31, 2005. Of these, 460 women died, 221 from breast cancer. Moderate and strenuous physical activities were combined into low (3.0 h/wk/y), or high activity (>3.0 h/wk/y of either activity type). Multivariable relative risks (RR) and 95% confidence intervals (95% CI) for mortality were estimated using Cox proportional hazards methods, adjusting for race/ethnicity, estrogen receptor status, disease stage, and baseline information on comorbidities, body mass index, and caloric intake. RESULTS: Women with high or intermediate levels of long-term physical activity had lower risk of breast cancer death (RR, 0.53; 95% CI, 0.35-0.80; and RR, 0.65; 95% CI, 0.45-0.93, respectively) than women with low activity levels. These associations were consistent across estrogen receptor status and disease stage, but were confined to overweight women. Deaths due to causes other than breast cancer were related only to recent activity. CONCLUSIONS: Consistent long-term participation in physical activity before breast cancer diagnosis may lower risk of breast cancer death, providing further justification for public health strategies to increase physical activity throughout the lifespan.

Association studies of common variants in 10 hypogonadotropic hypogonadism genes with age at menarche.

CONTEXT: Although the timing of puberty is a highly heritable trait, little is known about the genes that regulate pubertal timing in the general population. Several genes have been identified that, when mutated, cause disorders of delayed or absent puberty such as hypogonadotropic hypogonadism (HH). OBJECTIVE: Because severe variants in HH-related genes cause a severe puberty phenotype, we hypothesized that common subtle variation in these genes could contribute to the population variation in pubertal timing. DESIGN: We assessed common genetic variation in 10 HH-related genes in 1801 women from the Hawaii and Los Angeles Multiethnic Cohort with either early (age<11 yr) or late (age>14 yr) menarche and in other replication samples. In addition to these common variants, we also studied the most frequently reported HH mutations to assess their role in the population variation in pubertal timing. SETTING AND PATIENTS/OTHER PARTICIPANTS: Within the general community, 1801 women from the Hawaii and Los Angeles Multiethnic Cohort participated. MAIN OUTCOME MEASURES: We assessed the association of genetic variation with age at menarche. RESULTS: We found no significant association between any of the variants tested and age at menarche, although we cannot rule out modest effects of these variants or of other variants at long distances from the coding region. In several self-reported racial/ethnic groups represented in our study, we observed an association between estimated genetic ancestry and age at menarche. CONCLUSIONS: Our results suggest that common variants near 10 HH-related loci do not play a substantial role in the regulation of age at menarche in the general population.

Incomplete pregnancy is not associated with breast cancer risk: the California Teachers Study.

BACKGROUND: Early studies of incomplete pregnancy and development of breast cancer suggested that induced abortion might increase risk. Several large prospective studies, which eliminate recall bias, did not detect associations, but this relationship continues to be debated. STUDY DESIGN: To further inform this important question, we examined invasive breast cancer as it relates to incomplete pregnancy, including total number of induced abortions, age at first induced abortion and total number of miscarriages among women participating in the ongoing California Teachers Study (CTS) cohort. Incomplete pregnancy was self-reported on the CTS baseline questionnaire in 1995-1996. Incident breast cancers were ascertained in 3324 women through 2004 via linkage with the California Cancer Registry. RESULTS: Using Cox multivariable regression, we found no statistically significant association between any measure of incomplete pregnancy and breast cancer risk among nulliparous or parous women. CONCLUSION: These results provide strong evidence that there is no relationship between incomplete pregnancy and breast cancer risk.

Predictors of the timing of natural menopause in the Multiethnic Cohort Study.

The timing of natural menopause has implications for several health endpoints; in particular, it is a risk factor for breast cancer. The authors investigated factors influencing the timing of natural menopause among 95,704 women with a mean age of 59.7 years (10th-90th percentile range, 47.0-71.0) in five racial/ethnic groups in the Multiethnic Cohort Study, including non-Latina Whites, Japanese Americans, African Americans, Native Hawai'ians, and Latinas. The authors investigated whether race/ethnicity and several lifestyle and reproductive characteristics were associated with the timing of natural menopause. Race/ethnicity was a significant independent predictor of the timing of natural menopause. Other factors, including smoking, age at menarche, parity, and body mass index, did not significantly alter the race/ethnicity-specific hazard ratios. Relative to non-Latina Whites, natural menopause occurred earlier among Latinas (US-born Latinas: hazard ratio (HR) = 1.10, 95% confidence interval (CI): 1.07, 1.14; non-US-born Latinas: HR = 1.25, 95% CI: 1.21, 1.30) and later among Japanese Americans (HR = 0.93, 95% CI: 0.90, 0.95). These results support the hypothesis that the timing of natural menopause is driven by a combination of genetic, reproductive, and lifestyle factors.

Ethnic disparity in the relationship between obesity and plasma insulin-like growth factors: the multiethnic cohort.

Previous studies on the relationship between obesity and circulating insulin-like growth factor (IGF) hormones show inconsistent findings and have not considered the possibility of racial/ethnic-specific differences that may exist. We therefore examined the relationship between obesity status [as measured by body mass index (BMI)] and plasma levels of the IGF proteins, IGF-I, IGF-binding protein 3 (IGFBP-3), and the molar ratio of IGF-I/IGFBP-3 in Whites, African Americans, Latinos, Japanese Americans, and Native Hawaiians from the ongoing Hawaii and Los Angeles Multiethnic Cohort Study. We measured plasma IGF-I and IGFBP-3 by ELISA in a random sample of 811 Multiethnic Cohort participants (53% male, age range = 47-82 at blood draw). In a multivariate regression of IGF-I levels, we found a statistically significant interaction between race/ethnicity and obesity status (P = 0.005). Plasma IGF-I levels declined with increasing BMI most dramatically in Latinos and Japanese. This decline was attenuated in Whites and absent in African-American and Native Hawaiian subjects. In Japanese, the quadratic term (BMI(2)) was statistically significant in a multivariate model (P = 0.002). In Latinos, the adjusted least-squares mean IGF-I levels in ng/mL for BMI < 25, 25 to 29.99, and >or=30 were 184.6, 147.7, and 132.7, respectively. No interaction between race/ethnicity and BMI explained the plasma IGFBP-3 levels in these data. These results may help to resolve the uncertainty in the relationship between circulating IGF levels and obesity and highlight the potential importance of racial/ethnic-specific effects among these factors in explaining ethnic disparities in obesity-related cancers.