Explore the vast range of titles available.

To validate an established breast cancer incidence model in an independent prospective data set. After aligning time periods for follow-up, we restricted populations to comparable age ranges (47–74 years), and followed them for incident invasive breast cancer (follow-up 1994–2008, Nurses’ Health Study [NHS]; and 1995–2009, California Teachers Study [CTS]). We identified 2026 cases during 540,617 person years of follow-up in NHS, and 1,400 cases during 288,111 person years in CTS. We fit the Rosner–Colditz log-incidence model and the Gail model using baseline data. We imputed future use of hormones based on type and prior duration of use and other covariates. We assessed performance using area under the curve (AUC) and calibration methods. Participants in the CTS had fewer children, were leaner, consumed more alcohol, and were more frequent users of postmenopausal hormones. Incidence rate ratios for breast cancer showed significantly higher breast cancer in the CTS (IRR = 1.32, 95 % CI 1.24–1.42). Parameters for the log-incidence model were comparable across the two cohorts. Overall, the NHS model performed equally well when applied in the CTS. In the NHS the AUC was 0.60 (s.e. 0.006) and applying the NHS betas to the CTS the performance in the independent data set (validation) was 0.586 (s.e. 0.009). The Gail model gave values of 0.547 (s.e. 0.008), a significant 4 % lower, p  < 0.0001. For women 47–69 the AUC values for the log-incidence model are 0.608 in NHS and 0.609 in CTS; and for Gail are 0.569 and 0.572. In both cohorts, performance of both models dropped off in older women 70–87, and later in follow-up (6–12 years). Calibration showed good estimation against SEER with a non-significant 4 % underestimate of overall breast cancer incidence when applying the model in the CTS population ( p  = 0.098). The Rosner–Colditz model performs consistently well when applied in an independent data set. Performance is stronger predicting incidence among women 47–69 and over a 5-year time interval. AUC values exceed those for Gail by 3–5 % based on AUC when both are applied to the independent validation data set. Models may be further improved with addition of breast density or other markers of risk beyond the current model.

Background/Objectives: Data from previous studies consistently suggest that maternal smoking is positively associated with obesity later in life. Whether this association persists across generations is unknown. We examined whether grand-parental smoking was positively associated with overweight status in adolescence. Subject/Methods: Participants were grandmother-mother-child triads in the Nurses’ Health Study II (NHS II), the Nurses Mothers’ Cohort Study and the Growing up Today Study (GUTS). Grandmothers provided information on their and their partner’s smoking during pregnancy with the child’s mother. Information on child’s weight and height at ages 12 ( N =3094) and 17 ( N =3433) was obtained from annual or biennial GUTS questionnaires. We used logistic regression to estimate the odds ratios (ORs) of being overweight or obese, relative to normal weight. Results: Grand-maternal smoking during pregnancy was not associated with overweight status in adolescence. After adjusting for covariates, the OR of being overweight or obese relative to normal weight at age 12 years in girls whose grandmothers smoked 15+ cigarettes daily during pregnancy was 1.21 (95% confidence interval (CI) 0.74–1.98; P trend =0.31) and 1.07 (0.65–1.77; P trend =0.41) in boys. Grand-paternal smoking during pregnancy was associated with being overweight or obese at age 12 in girls only, but not at age 17 for either sex: the OR for being overweight or obese at age 12 was 1.38 (95% CI 1.01–1.89; P trend =0.03) in girls and 1.31 (95% CI 0.97–1.76; P trend =0.07) in boys. Among children of non-smoking mothers, the OR for granddaughter obesity for grand-paternal smoking was attenuated and no longer significant (OR 1.28 (95% CI 0.87–1.89; P trend =0.18)). Conclusions: Our findings suggest that the association between maternal smoking and offspring obesity may not persist beyond the first generation. However, grand-paternal smoking may affect the overweight status of the granddaughter, likely through the association between grand-paternal smoking and maternal smoking.

Evidence suggests that nutrients involved in one-carbon metabolism are implicated in ovarian cancer etiology. No studies have evaluated the role of choline, and that of its metabolite, betaine. We prospectively examined the relationship between the intake of these nutrients and ovarian cancer risk among 159 957 participants from the Nurses’ Health Study (NHS) and NHSII. The average nutrient intake was assessed every 2–4 years beginning in 1984 (for NHS) and in 1991 (for NHSII). With up to 22 years of follow-up per cohort, 526 incident cases of ovarian cancer were diagnosed. There were no associations between total choline, betaine, as well as choline plus betaine intake and ovarian cancer risk (for example, relative risk, top vs bottom quintile of choline=0.98; 95% confidence interval: 0.73–1.31; Ptrend=0.81). Results did not vary by alcohol consumption, folate intake or after the exclusion of cases diagnosed during the 4-year period after dietary assessment. These data provide little evidence for a role of these nutrients in ovarian cancer etiology.

Objectives: Increased breast cancer risk has been observed with both low folate status and a functional polymorphism in methylenetetrahydrofolate reductase (MTHFR 677C leads to T). Cytoplasmic serine hydroxymethyltransferase (cSHMT) affects the flow of one-carbon units through the folate metabolic network, but there is little research on a role for genetic variation in cSHMT in determining breast cancer risk. Methods: A nested case–control study within the Nurses' Health Study was used to investigate an association between cSHMT (1420C leads to T) and breast cancer risk. Results: No evidence for an association between the cSHMT genotype and breast cancer was observed. There was also no evidence of a gene–gene interaction between cSHMT and MTHFR. Conclusions: There was no evidence of an association between the cSHMT genotype and breast cancer occurrence. Further research in populations with differing average folate intake may be required to fully understand the interactions of folate nutrition, sequence variation in folate genes and breast cancer risk.

Background. The relation between body weight and overall mortality remains controversial despite considerable investigation. Methods. We examined the association between body-mass index (defined as the weight in kilograms divided by the square of the height in meters) and both overall mortality and mortality from specific causes in a cohort of 115,195 U.S. women enrolled in the prospective Nurses' Health Study. These women were 30 to 55 years of age and free of known cardiovascular disease and cancer in 1976. During 16 years of follow-up, we documented 4726 deaths, of which 881 were from cardiovascular disease, 2586 from cancer, and 1259 from other causes. Results. In analyses adjusted only for age, we observed a J-shaped relation between body-mass index and overall mortality. When women who had never smoked were examined separately, no increase in risk was observed among the leaner women, and a more direct relation between weight and mortality emerged (P for trend 0.001). In multivariate analyses of women who had never smoked and had recently had stable weight, in which the first four years of follow-up were excluded, the relative risks of death from all causes for increasing categories of body-mass index were as follows: body-mass index 19.0 (the reference category), relative risk

The objective of this study is to examine perinatal correlates of oestradiol (E2), oestriol (E3), progesterone and sex hormonebinding globulin (SHBG) among pregnant women in the USA and China. Three hundred and four Caucasian women in Boston and 335 Chinese women in Shanghai were studied. Levels of E2, E3, progesterone and SHBG were measured in maternal blood at weeks 16 and 27 of gestation, and correlated with maternal, gestational and perinatal characteristics. Height, weight and body mass index (BMI) before pregnancy is inversely associated with E2 and SHBG, whereas E 3 is inversely associated with height and progesterone is inversely associated with weight and BMI. A previous live birth is associated with lower E2 and SHBG in the index pregnancy. Total gestation duration is inversely associated with E2, E3 and progesterone, whereas weight gain during pregnancy is inversely associated with progesterone and SHBG. In the US, pregnancies with female fetuses are characterized by significantly reduced progesterone. Pregnancy hormones are associated with several maternal, gestational and neonatal characteristics.

Summary Background The relation between breastfeeding and breast-cancer risk has been examined in many studies; some have reported no association, and others a reduced risk, particularly among premenopausal women. In the only prospective cohort study, no association was found. We have assessed prospectively the association between breastfeeding and incidence of breast cancer among 89887 women in the US Nurses' Health Study. Methods In 1986, participants were asked about the number of months they breastfed for all their children combined. Parous women with no history of cancer were included in this analysis. During 6 years of follow-up (513015 person-years), 1459 invasive breast cancer cases were diagnosed. Findings Relative to women who had never breastfed, no significant overall association was found—after adjusting for established risk factors for breast cancer—between a history of having breastfed and subsequent development of breast cancer (relative risk [RR] 0·93, 95% Cl 0·83-1·03). No inverse trend was observed with duration of breastfeeding; women who breastfed for 2 years or longer had a RR of 1·11 (0·90-1·38). Among women who had given birth only once, women who had breastfed their child experienced a lower incidence of breast cancer (RR 0·68, 0·46-1·00). Among premenopausal women, who tended to be near menopause due to the age structure of the cohort, the RR of breast cancer for those who had lactated was 1·16 (0·89-1·50). Premenopausal women who had lactated for 1 year or more had a RR of 1·10 (0·78-1·57). Interpretation These data suggest that there is no important overall association between breast-feeding and the occurrence of breast cancer.

The objective of this study is to determine correlates of prolactin and growth hormone levels among pregnant women in the USA and China. We studied 304 pregnant Caucasian and 335 pregnant Chinese women. Levels of prolactin and growth hormone were measured at weeks 16 and 27 of gestation, and correlated with maternal, gestational and perinatal characteristics. Both growth hormone and, to a lesser extent, prolactin were inversely associated with pregnancy weight and body mass index, history of a previous live birth and newborn size, whereas educated women had higher levels of both hormones. Growth hormone levels were lower in women who gained more weight, smoked and had nausea and vomiting during pregnancy, whereas prolactin increased with longer total gestation. We found robust associations between maternal and newborn characteristics on the one hand and prolactin and growth hormone during pregnancy on the other.