Association of oral contraceptives and tubal ligation with risk of early natural menopause.

STUDY QUESTION: What is the association of oral contraceptives (OCs) and tubal ligation (TL) with early natural menopause? SUMMARY ANSWER: We did not observe an association of OC use with risk of early natural menopause; however, TL was associated with a modestly higher risk. WHAT IS KNOWN ALREADY: OCs manipulate hormone levels, prevent ovulation, and may modify the rate of follicular atresia, while TL may disrupt the blood supply to the ovaries. These mechanisms may be associated with risk of early menopause, a condition associated with increased risk of cardiovascular disease and other adverse health outcomes. STUDY DESIGN, SIZE, DURATION: We examined the association of OC use and TL with natural menopause before the age of 45 years in a population-based study within the prospective Nurses' Health Study II (NHSII) cohort. Participants were followed from 1989 to 2017 and response rates were 85-90% for each cycle. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants included 106 633 NHSII members who were premenopausal and aged 25-42 years at baseline. Use, duration and type of OC, and TL were measured at baseline and every 2 years. Menopause status and age were assessed every 2 years. Follow-up continued until early menopause, age 45 years, hysterectomy, oophorectomy, death, cancer diagnosis, or loss to follow-up. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% CIs adjusted for lifestyle, dietary, and reproductive factors. MAIN RESULTS AND THE ROLE OF CHANCE: Over 1.6 million person-years, 2579 members of the analytic cohort experienced early natural menopause. In multivariable models, the duration, timing, and type of OC use were not associated with risk of early menopause. For example, compared with women who never used OCs, those reporting 120+ months of OC use had an HR for early menopause of 1.01 (95% CI, 0.87-1.17; P for trend=0.71). TL was associated with increased risk of early menopause (HR = 1.17, 95% CI, 1.06-1.28). LIMITATIONS, REASONS FOR CAUTION: Our study population is homogenous with respect to race and ethnicity. Additional evaluation of these relations in more diverse populations is important. WIDER IMPLICATIONS OF THE FINDINGS: To our knowledge, this is the largest study examining the association of OC use and TL with early natural menopause to date. While TL was associated with a modest higher risk of early menopause, our findings do not support any material hazard or benefit for the use of OCs. STUDY FUNDING/COMPETING INTEREST(S): The study was sponsored by UO1CA176726 and R01HD078517 from the National Institutes of Health and Department of Health and Human Services. The work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The authors have no competing interests to report. TRIAL REGISTRATION NUMBER: N/A.

Associations of early life and adulthood adiposity with risk of epithelial ovarian cancer.

BACKGROUND: Few studies have evaluated the association between early life adiposity and ovarian cancer risk. Adiposity during different periods of life may be differentially associated with the risk. PATIENTS AND METHODS: We prospectively followed 133 526 women in the Nurses' Health Study (NHS; 1980-2012) and NHSII (1989-2013). Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident ovarian cancer (N = 788) according to validated measures for early life adiposity [body mass index (BMI) at age 10 imputed from somatotype and recalled BMI at age 18) as well as BMI change between age 10 and 18 and after age 18 (current weight assessed on every biennial questionnaire since baseline). RESULTS: After mutual adjustment for BMI at age 10, BMI at age 18 and current BMI, the HR (95% CI) for ovarian cancer risk per 5 kg/m2 was 0.84 (0.74-0.96) for BMI at age 10 (P-trend = 0.01), 1.17 (1.03-1.33) for BMI at age 18 (P-trend = 0.02), and 1.06 (0.99-1.14) for current BMI (P-trend = 0.08). However, the inverse association with BMI at age 10 was attenuated after adjusting for BMI change between age 10 and 18 and BMI change after age 18 (HR per 5 kg/m2: 1.04; 95% CI 0.91-1.20; P-trend = 0.55). By contrast, BMI change between age 10 and 18 was strongly positively associated with ovarian cancer risk (HR per 5 kg/m2 increase: 1.24; 95% CI 1.11-1.39; P-trend = 0.0002), whereas BMI change since age 18 was only slightly associated with risk (HR per 5 kg/m2 increase: 1.06; 95% CI 0.99-1.14; P-trend = 0.10). These associations were in general stronger for premenopausal cases or non-serous tumors. CONCLUSION: Early life changes in adiposity were more strongly associated with ovarian cancer risk than adulthood changes. The specific mechanisms underlying the associations with adiposity changes during early life warrant further investigation.

Adult adiposity and risk of early menopause.

STUDY QUESTION: Is adult adiposity associated with early menopause? SUMMARY ANSWER: Overall and abdominal adiposity were non-linearly associated with odds for early natural menopause with elevated odds observed among women who were underweight in early or mid-adulthood compared to lean-normal weight women. WHAT IS KNOWN ALREADY: High and low adiposity have been associated with reproductive function and may potentially impact timing of menopause. It is unclear whether various aspects of adiposity are associated with risk of early menopause. STUDY DESIGN, SIZE, DURATION: Prospective cohort study that examined data from 78 759 premenopausal women from the Nurses' Health Study II who were followed from 1989 to 2011 for incidence of early natural menopause. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were aged 25-42 years and premenopausal at baseline in 1989, when information on menopausal status, height and weight was reported via questionnaire. Information on menopausal status, type of menopause (natural, surgical, radiation/chemotherapy), hormone therapy use and weight was updated every two years along with information on smoking, physical activity and other behavioral and health-related factors. Multivariable logistic regression was used to estimate odds ratios for early menopause, defined as natural menopause before age 45 years, by aspects of adiposity. MAIN RESULTS AND THE ROLE OF CHANCE: Early natural menopause was reported by 2804 participants. Body mass index (BMI) was non-linearly associated with risk for early menopause. Compared to women with BMI = 18.5-22.4 kg/m2, those with BMI < 18.5 kg/m2 had a significant 30% higher odds of early menopause (95% confidence interval (CI) = 1.08, 1.57), while women with BMIs between 25.0-29.9 kg/m2 had significant 21-30% lower odds. Odds were not higher in women with BMI ≥ 35.0 kg/m2 in fully adjusted analysis. Non-linear associations with higher odds in underweight women were also observed for age 18 and age 35 BMI, though lower odds for overweight women was only observed for age 35 BMI. Odds were highest among women with age 18 BMI < 18.5 kg/m2 reporting severe weight cycling. LIMITATIONS, REASONS FOR CAUTION: Though weight and early menopause status were self-reported, validation studies conducted among Nurses' Health Study participants suggest that self-reported weight is highly correlated with directly measured weight, and prospective self-reported menopausal status is highly reproducible. It is possible that underweight women may have been misclassified with an earlier age at menopause if being underweight led to amenorrhea. WIDER IMPLICATIONS OF THE FINDINGS: In one of the few studies to prospectively examine a variety of adiposity measures and risk for early menopause, our findings that women who were underweight in early or mid-adulthood had elevated risk for early menopause can assist in efforts to better understand the etiology of early menopause. Additional prospective research is needed to understand how low adiposity may physiologically impact timing of menopause. STUDY FUNDING/COMPETING INTEREST(S): This study was conducted with funding from NIH UM1CA176726 and R01HD078517. The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: Not applicable.

Validation of Rosner-Colditz breast cancer incidence model using an independent data set, the California Teachers Study.

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.

A prospective study of dietary carbohydrate quantity and quality in relation to risk of ovulatory infertility.

OBJECTIVE: To evaluate whether the amount or quality of carbohydrate in diet is associated with ovulatory infertility. SUBJECTS AND METHODS: In total, 18,555 married, premenopausal women without a history of infertility were followed as they attempted a pregnancy or became pregnant during an 8-year period. Diet was assessed two times during follow-up using a validated food-frequency questionnaire and prospectively related to the incidence of infertility due ovulatory disorder. RESULTS: During follow-up, 438 women reported ovulatory infertility. Total carbohydrate intake and dietary glycemic load were positively related to ovulatory infertility in analyses adjusted for age, body mass index, smoking, parity, physical activity, recency of contraception, total energy intake, protein intake and other dietary variables. The multivariable-adjusted risk ratio (RR) (95% confidence interval (CI)) of ovulatory infertility comparing the highest-to-lowest quintile of total carbohydrate intake was 1.91 (1.27-3.02). The corresponding RR (95% CI) for dietary glycemic load was 1.92 (1.26-2.92). Dietary glycemic index was positively related to ovulatory infertility only among nulliparous women. Intakes of fiber from different sources were unrelated to ovulatory infertility risk. CONCLUSIONS: The amount and quality of carbohydrate in diet may be important determinants of ovulation and fertility in healthy women.

Comparison of aspects of smoking among the four histological types of lung cancer.

BACKGROUND: The magnitude of the link between cigarette smoking and lung cancer may vary by histological type. METHODS: We used polytomous logistic regression to evaluate whether aspects of smoking have different effects across four histological types in the Nurses' Health Study. RESULTS: From 1976 to 2002, we identified 1062 cases of lung cancer: squamous cell (n = 201), small cell (n = 236), adenocarcinoma (n = 543) and large cell carcinoma (n = 82), among 65 560 current or former smokers. Risk reduction after quitting ranged from an 8% reduction (relative risk (RR): 0.92, 95% CI 0.91 to 0.94) to a 17% reduction (RR: 0.83, 95% CI 0.80 to 0.86) per year for adenocarcinoma and small cell carcinoma, respectively, with a 9% reduction observed for large cell carcinoma and an 11% reduction observed for squamous cell carcinoma. The association of age at smoking initiation and former cigarette smoking was similar across types, while the association of smoking duration differed. The risk of adenocarcinoma increased by 6% per year of smoking, compared to 7% for large cell, 10% for squamous cell and 12% for small cell. The 6% difference between adenocarcinoma and small cell carcinoma is equivalent to a 3.2 to 9.7-fold increase in risk for 20 years of smoking. CONCLUSIONS: The effects of the number of cigarettes smoked per day and years since quitting smoking are different across the major types of lung cancer, which are fully appreciated at long durations of smoking and smoking cessation. Smoking prevention and cessation should continue to be the focus of public health efforts to reduce lung cancer incidence and mortality.

A prospective study of postmenopausal hormone use and ovarian cancer risk.

The relationship between postmenopausal hormone use (PMH) and ovarian cancer risk is unclear, particularly for specific hormone formulations, but recent studies suggest that there is a positive association. We conducted a prospective observational study with 82,905 postmenopausal women, including 389 ovarian cancers, in the Nurses' Health Study from 1976 to 2002. Compared with never users of PMH, both current and past users of > or =5 years had a significantly elevated risk of ovarian cancer (RR=1.41, 95% confidence interval (CI) 1.07-1.86 and relative risk (RR)=1.52, 95% CI 1.01-2.27, respectively). Examined by hormone type in continuous years, use of unopposed estrogen was associated with a significant increase in the risk of epithelial ovarian cancer (P for trend <0.001; RR for 5-year increment of use=1.25, 95% CI 1.12-1.38). Use of estrogen plus progestin (RR for 5-year increment of use=1.04, 95% CI 0.82-1.32) was not significantly associated with ovarian cancer risk. Generally, results were similar for serous tumours (RR for 5-year increment of unopposed estrogen use=1.23, 95% CI 1.07-1.40) and slightly stronger for endometrioid tumours (RR for 5-year increment of unopposed estrogen use=1.53, 95% CI 1.20-1.94). Recency of use was not significantly associated with ovarian cancer risk, but statistical power was limited here.

Risk of ovarian carcinoma and consumption of vitamins A, C, and E and specific carotenoids: a prospective analysis.

BACKGROUND: Antioxidant vitamins may decrease risk of cancer by limiting oxidative DNA damage leading to cancer initiation. Few prospective studies have assessed relations between antioxidant vitamins and ovarian carcinoma. METHODS: The authors prospectively assessed consumption of vitamins A, C, and E and specific carotenoids, as well as fruit and vegetable intake, in relation to ovarian carcinoma risk among 80,326 participants in the Nurses' Health Study who had no history of cancer other than nonmelanoma skin carcinoma. Women reported on known and suspected ovarian carcinoma risk factors including reproductive factors, smoking, and use of vitamin supplements on biennial mailed questionnaires from 1976 to 1996. Food frequency questionnaires were included in 1980, 1984, 1986, and 1990. The authors confirmed 301 incident cases of invasive epithelial ovarian carcinoma during 16 years of dietary follow-up (1980-1996). Pooled logistic regression was used to control for age, oral contraceptive use, body mass index, smoking history, parity, and tubal ligation. RESULTS: The authors observed no association between ovarian carcinoma risk and antioxidant vitamin consumption from foods, or foods and supplements together. The multivariate relative risks (95% confidence intervals [CIs]) for ovarian carcinoma among women in the highest versus lowest quintile of intake were 1.04 (95% CI, 0.72-1.51) for vitamin A from foods and supplements; 1.01 (95% CI, 0.69-1.47) for vitamin C; 0.88 (95% CI, 0.61-1.27) for vitamin E; and 1.10 (95% CI, 0.76-1.59) for beta-carotene. Among users of vitamin supplements, the authors found no evidence of an association between dose or duration of any specific vitamin and ovarian carcinoma risk, although the authors had limited power to assess these relations. No specific fruits or vegetables were associated significantly with ovarian carcinoma risk. The authors found no association between ovarian carcinoma and consumption of total fruits or vegetables, or specific subgroups including cruciferous vegetables, green leafy vegetables, legumes, or citrus fruits. Women who consumed at least 2.5 total servings of fruits and vegetables as adolescents had a 46% reduction in ovarian carcinoma risk (relative risk, 0.54, 95% CI, 0.29-1.03; P value for trend 0.04). CONCLUSIONS: These data do not support an important relation between consumption of antioxidant vitamins from foods or supplements, or intake of fruits and vegetables, and incidence of ovarian carcinoma in this cohort. However, modest associations cannot be excluded, and the authors' finding of an inverse association for total fruit and vegetable intake during adolescence raises the possibility that the pertinent exposure period may be much earlier than formerly anticipated.

Prospective study of recreational physical activity and ovarian cancer.

BACKGROUND: It has been hypothesized that physical activity may reduce the risk of ovarian cancer by decreasing estrogen levels, reducing body fat, and reducing the frequency of ovulation. Epidemiologic studies of this relationship have obtained inconsistent results. The only prospective study to date reported a positive association between frequent vigorous exercise and ovarian cancer risk. We further evaluated this relationship in the Nurses' Health Study cohort. METHODS: Participation in recreational physical activity was assessed by questionnaire in 1980, 1982, 1986, 1988, 1992, and 1994, with questions assessing exercise frequency, duration, and intensity. Results were adjusted for age, parity, oral contraceptive use, tubal ligation, and other risk factors for ovarian cancer. All statistical tests were two-sided. RESULTS: During a 16-year follow-up (from 1980 to 1996), 1.2 million person-years were accrued by 92 825 cohort members, and 377 cases of epithelial ovarian cancer were confirmed. The relative risk (RR) of ovarian cancer for women engaging in recreational physical activity for 7 hours or more per week compared with those reporting less than 1 hour per week was 0.80 (95% confidence interval [CI] = 0.49 to 1.32; P(trend) =.59). When both the frequency and intensity of activity were taken into account, activity level was also not associated with a reduced risk of ovarian cancer. Compared with inactive women, participants reporting high activity in terms of metabolic equivalent task hours (MET hours) were at greater risk of ovarian cancer (RR for 20 to <30 MET hours/week = 1.84 [95% CI = 1.12 to 3.02]; RR for >30 MET hours/week = 1.27 [95% CI = 0.75 to 2.14]). CONCLUSIONS: Overall, results did not suggest an inverse association between recreational physical activity and ovarian cancer. The possibility of a modest increase in risk with frequent vigorous activity requires further investigation.

Factors that influence the decision to do an adequate evaluation of a patient with a positive stool for occult blood.

OBJECTIVE: The factors that influence the decision to do an adequate evaluation for a positive test for fecal occult blood in a middle-aged or elderly patient are largely unknown. Our study was undertaken to determine whether factors such as the number of positive Hemoccult II card windows, age, gender, family history of colon cancer, the patient's concern that he or she might have colon cancer, or history of rectal bleeding influence the evaluation performed. METHOD: A mass screening program for colon cancer was performed using unrehydrated Hemoccult II cards in the Boston area. RESULTS: Among the 23,593 Hemoccult II cards returned to Beth Israel Deaconess Medical Center, cards from 1,112 patients (4.7%) were found to be positive for one or more of the six possible card windows. Ninety percent, or 940 patients, over 40 yr of age had follow-up information available. As the number of positive windows increased from one to four, there was a significant trend (p < 0.001) for the adequacy of the evaluation to increase. Family history (p = 0.044) and a patient's worry that he or she might have colon cancer (p = 0.003) significantly improved a patient's chance for an adequate evaluation. CONCLUSIONS: Hemoccult testing is not followed by an adequate evaluation in a significant proportion of patients. Our study points out for the first time that the number of positive Hemoccult windows significantly influences the decision-making.

Being breastfed in infancy and breast cancer incidence in adult life: results from the two nurses' health studies.

Events during perinatal and early life may influence the incidence of breast cancer in adult life, and some case-control studies suggest that having been breastfed may reduce breast cancer risk. The authors studied this association among premenopausal and postmenopausal women by using data from the two Nurses' Health Studies, the Nurses' Health Study (using data from 1992 to 1996) and the Nurses' Health Study II (using data from 1991 to 1997). A history of being breastfed was self-reported by the study participants. During a total of 695,655 person-years, 1,073 cases of invasive breast cancer were diagnosed. The authors did not observe any important overall association between having been breastfed and the development of breast cancer later in life among premenopausal women (covariate-adjusted relative risk = 0.97, 95% confidence interval (CI): 0.78, 1.20) or postmenopausal women (covariate-adjusted relative risk = 1.12, 95% CI: 0.92, 1.37). No significant trend was observed with increasing duration of breastfeeding. The authors also used data on breastfeeding retrospectively collected from 2,103 mothers of participants of the two Nurses' Health Studies. With the mothers' reports, the covariate-adjusted odds ratio of breast cancer was 1.11 (95% CI: 0.88, 1.39) for women who were breastfed compared with those who were not. Data from these two large cohorts do not support the hypothesis that being breastfed confers protection against subsequent breast cancer.

Prospective study of fruit and vegetable consumption and incidence of colon and rectal cancers.

BACKGROUND: Frequent consumption of fruit and vegetables has been associated with a reduced risk of colorectal cancer in many observational studies. METHODS: We prospectively investigated the association between fruit and vegetable consumption and the incidence of colon and rectal cancers in two large cohorts: the Nurses' Health Study (88 764 women) and the Health Professionals' Follow-up Study (47 325 men). Diet was assessed and cumulatively updated in 1980, 1984, 1986, and 1990 among women and in 1986 and 1990 among men. The incidence of cancer of the colon and rectum was ascertained up to June or January of 1996, respectively. Relative risk (RR) estimates were calculated with the use of pooled logistic regression models accounting for various potential confounders. All statistical tests were two-sided. RESULTS: With a follow-up including 1 743 645 person-years and 937 cases of colon cancer, we found little association of colon cancer incidence with fruit and vegetable consumption. For women and men combined, a difference in fruit and vegetable consumption of one additional serving per day was associated with a covariate-adjusted RR of 1.02 (95% confidence interval [CI] = 0.98-1.05). A difference in vegetable consumption of one additional serving per day was associated with an RR of 1.03 (95% CI = 0.97-1.09). Similar results were obtained for women and men considered separately. A difference in fruit consumption of one additional serving per day was associated with a covariate-adjusted RR for colon cancer of 0.96 (95% CI = 0.89-1.03) among women and 1. 08 (95% CI = 1.00-1.16) among men. For rectal cancer (total, 244 cases), a difference in fruit and vegetable consumption of one additional serving per day was associated with an RR of 1.02 (95% CI = 0.95-1.09) in men and women combined. None of these associations was modified by vitamin supplement use or smoking habits. CONCLUSIONS: Although fruits and vegetables may confer protection against some chronic diseases, their frequent consumption does not appear to confer protection from colon or rectal cancer.

Adherence to the Dietary Guidelines for Americans and risk of major chronic disease in women.

BACKGROUND: Little is known about the overall health effects of adherence to the Dietary Guidelines for Americans. The healthy eating index (HEI), developed at the US Department of Agriculture, measures how well Americans' diets conform to these guidelines. OBJECTIVE: We tested whether the HEI (scores range from 0 to 100; 100 is best) calculated from food-frequency questionnaires (HEI-f) would predict risk of major chronic disease in women. DESIGN: A total of 67272 US female nurses who were free of major disease completed detailed questionnaires on diet and chronic disease risk factors in 1984 and repeatedly over 12 y. Major chronic disease was defined as fatal or nonfatal cardiovascular disease (myocardial infarction or stroke, n = 1365), fatal or nonfatal cancer (n = 5216), or other nontraumatic deaths (n = 496), whichever came first. We also examined cardiovascular disease and cancer as separate outcomes. RESULTS: After adjustment for smoking and other risk factors, the HEI-f score was not associated with risk of overall major chronic disease in women [relative risk (RR) = 0.97; 95% CI: 0.89, 1.06 comparing the highest with the lowest quintile of HEI-f score]. Being in the highest HEI-f quintile was associated with a 14% reduction in cardiovascular disease risk (RR = 0.86; 95% CI: 0.72, 1. 03) and was not associated with lower cancer risk (RR = 1.02; 95% CI: 0.93, 1.12). CONCLUSION: These data suggest that adherence to the 1995 Dietary Guidelines for Americans, as measured by the HEI-f, will have limited benefit in preventing major chronic disease in women.

Combining annual blood pressure measurements in childhood to improve prediction of young adult blood pressure.

Tracking correlations of blood pressure (BP) have been reported between levels measured in a single year during both childhood and adulthood. Because of the variability of BP, these correlations increase with the number of visits and measurements per visit in each year. It remains unclear, however, whether such correlations would improve further by combining BP data collected over several years. From 1978-1981, BP was measured annually in a cohort of 339 children in East Boston, MA, at four visits one week apart with three measurements per visit. Of this cohort, then aged 18-26 years, 316 were re-examined in 1989-1990 at three visits one week apart with three measures per visit. Tracking correlations were estimated from levels measured in a single year as well as means averaged over several years in childhood, adjusting for age, year of measurement, as well as smoking, alcohol and oral contraceptive use. Multivariate models were fit to estimate tracking correlations from childhood to young adulthood adjusting for within-person variability. Using a single year in childhood, these were 0.49 in boys and 0.59 in girls for systolic BP and 0.39 and 0.48 for diastolic BP (all p<0.001). Using the long-term average in childhood and adjusting for variability across years, these values were 0.55 in boys and 0.66 in girls for systolic BP and 0.47 and 0.57 for diastolic BP (all p<0.001). We observed concomitant increases in the predictive value of childhood BP for young adult BP. These results suggest that averaging BP over at least two years during childhood increases tracking correlations and improves the prediction of adult values from childhood levels.

Intakes of fruits, vegetables, and related nutrients and the risk of non-Hodgkin's lymphoma among women.

Non-Hodgkin's lymphoma is etiologically related to suppressed immune status, and certain nutrients found in fruits and vegetables have been associated with increased immune responses. However, limited information exists on associations between intake of fruits, vegetables, and related nutrients and non-Hodgkin's lymphoma risk. We thus examined these associations among 88,410 women in the Nurses' Health Study cohort who were aged 34-60 years in 1980 and provided dietary information in 1980. During 14 years of follow-up, we documented 199 incident cases of non-Hodgkin's lymphoma. Higher intake of fruits and vegetables was associated with a lower risk of non-Hodgkin's lymphoma (P for trend = 0.02); the multivariate relative risk (RR) was 0.62 [95% confidence interval (CI), 0.38-1.02] for women who consumed greater than or equal to six servings per day as compared with those consuming less than three servings per day. When fruits and vegetables were examined separately, intake of vegetables rather than fruits was most clearly associated with a reduced risk (P for trend = 0.02 for vegetables; P for trend = 0.16 for fruits); compared with those consuming less than one serving per day, the multivariate RRs were 0.62 (95% CI, 0.35-1.07) for women who consumed greater than or equal to three servings per day of vegetables and 0.70 (95% CI, 0.44-1.12) for women who consumed this amount of fruits. Higher intake of cruciferous vegetables was also associated with a decreased risk (P for trend = 0.03); the multivariate RR was 0.67 (95% CI, 0.40-1.11) for women who consumed greater than or equal to five servings per week as compared with those consuming less than two servings per week. These associations were slightly attenuated when we additionally adjusted for intake of beef, pork, or lamb as a main dish. Intake of dietary fiber from vegetable sources was related to a reduced risk; the multivariate RR was 0.54 (95% CI, 0.34-0.87) for women in the highest quintile as compared with those in the lowest quintile (P for trend = 0.01), and it was slightly attenuated with additional adjustment for saturated and trans unsaturated fats. However, we observed no associations between intakes of specific dietary carotenoids, vitamins A, C, E, and folate, and non-Hodgkin's lymphoma risk. Higher intake of vegetables, particularly cruciferous vegetables, may reduce the risk of non-Hodgkin's lymphoma among women.

Dietary fat and protein in relation to risk of non-Hodgkin's lymphoma among women.

BACKGROUND: Non-Hodgkin's lymphoma occurs more frequently in individuals with suppressed immune status, and some types of dietary fat and protein have been associated with decreased immune responses. In this study, we examined the intake of specific types of dietary fat and protein in relation to the risk of non-Hodgkin's lymphoma. METHODS: We documented 199 incident cases of non-Hodgkin's lymphoma in a cohort of 88 410 women, who were enrolled in the Nurses' Health Study and were aged 34-60 years in 1980, during 14 years of follow-up. Relative risks of the disease and 95% confidence intervals (95% CIs) were calculated. All P values are two-sided and were considered to be statistically significant for P<.05. RESULTS: Intake of saturated fat was associated with an increase in risk that was not statistically significant; the multivariate relative risk for the highest versus the lowest quintiles of intake was 1.4 (95% CI = 0.7-3.0; P for trend =.42). Intake of beef, pork, or lamb as a main dish was associated with a statistically significantly increased risk of non-Hodgkin's lymphoma; the multivariate relative risk for consumption of these meats at least once per day as compared with less than once per week was 2.2 (95% CI = 1.1-4.4; P for trend =.002). Higher intake of trans unsaturated fat was also statistically significantly associated with an increased risk of the disease; the multivariate relative risk for the highest versus the lowest quintiles was 2.4 (95% CI = 1.3-4.6; P for trend =.01). Higher intake of red meat cooked by broiling or barbecuing-but not by roasting, pan-frying, or boiling or stewing-was associated with an increase in risk that was not statistically significant. CONCLUSIONS: Greater dietary intake of certain meats and fats was associated with a higher risk of non-Hodgkin's lymphoma. These relationships and their potential mechanisms deserve further examination.

A prospective study of folate intake and the risk of breast cancer.

CONTEXT: Folate is involved in DNA synthesis and methylation and may reduce breast cancer risk, particularly among women with greater alcohol consumption. OBJECTIVES: To assess the association between folate intake and risk of breast cancer and whether higher folate intake may reduce excess risk among women who consume alcohol. DESIGN: Prospective cohort study performed in 1980, with 16 years of follow-up. SETTING AND PARTICIPANTS: A total of 88818 women who completed the dietary questionnaire section of the Nurses' Health Study in 1980. MAIN OUTCOME MEASURE: Incidence of invasive breast cancer by levels of folate and alcohol intake. RESULTS: A total of 3483 cases of breast cancer were documented. Total folate intake was not associated with overall risk of breast cancer. However, among women who consumed at least 15 g/d of alcohol, the risk of breast cancer was highest among those with low folate intake. For total folate intake of at least 600 microg/d compared with 150 to 299 microg/d, the multivariate relative risk (RR) was 0.55 (95% confidence interval [CI], 0.39-0.76; P for trend = .001). This association was only slightly attenuated after additional adjustment for intake of beta carotene, lutein/zeaxanthin, preformed vitamin A, and total vitamins C and E. The risk of breast cancer associated with alcohol intake was strongest among women with total folate intake of less than 300 microg/d (for alcohol intake > or =15 g/d vs <15 g/d, multivariate RR, 1.32; 95% CI, 1.15-1.50). For women who consumed at least 300 microg/d of total folate, the multivariate RR for intake of at least 15 g/d of alcohol vs less than 15 g/d was 1.05 (95% CI, 0.92-1.20). Current use of multivitamin supplements, the major source of folate, was associated with lower breast cancer risk among women who consumed at least 15 g/d of alcohol (for current users of supplements vs never users, RR, 0.74; 95% CI, 0.59-0.93). CONCLUSIONS: Our findings suggest that the excess risk of breast cancer associated with alcohol consumption may be reduced by adequate folate intake.

A prospective study of egg consumption and risk of cardiovascular disease in men and women.

CONTEXT: Reduction in egg consumption has been widely recommended to lower blood cholesterol levels and prevent coronary heart disease (CHD). Epidemiologic studies on egg consumption and risk of CHD are sparse. OBJECTIVE: To examine the association between egg consumption and risk of CHD and stroke in men and women. DESIGN AND SETTING: Two prospective cohort studies, the Health Professionals Follow-up Study (1986-1994) and the Nurses' Health Study (1980-1994). PARTICIPANTS: A total of 37851 men aged 40 to 75 years at study outset and 80082 women aged 34 to 59 years at study outset, free of cardiovascular disease, diabetes, hypercholesterolemia, or cancer. MAIN OUTCOME MEASURES: Incident nonfatal myocardial infarction, fatal CHD, and stroke corresponding to daily egg consumption as determined by a food-frequency questionnaire. RESULTS: We documented 866 incident cases of CHD and 258 incident cases of stroke in men during 8 years of follow-up and 939 incident cases of CHD and 563 incident cases of stroke in women during 14 years of follow-up. After adjustment for age, smoking, and other potential CHD risk factors, we found no evidence of an overall significant association between egg consumption and risk of CHD or stroke in either men or women. The relative risks (RRs) of CHD across categories of intake were less than 1 per week (1.0), 1 per week (1.06), 2 to 4 per week (1.12), 5 to 6 per week (0.90), and > or =1 per day (1.08) (P for trend = .75) for men; and less than 1 per week (1.0), 1 per week (0.82), 2 to 4 per week (0.99), 5 to 6 per week (0.95), and > or =1 per day (0.82) (P for trend = .95) for women. In subgroup analyses, higher egg consumption appeared to be associated with increased risk of CHD only among diabetic subjects (RR of CHD comparing more than 1 egg per day with less than 1 egg per week among diabetic men, 2.02 [95% confidence interval, 1.05-3.87; P for trend = .04], and among diabetic women, 1.49 [0.88-2.52; P for trend = .008]). CONCLUSIONS: These findings suggest that consumption of up to 1 egg per day is unlikely to have substantial overall impact on the risk of CHD or stroke among healthy men and women. The apparent increased risk of CHD associated with higher egg consumption among diabetic participants warrants further research.

Dietary carotenoids and vitamins A, C, and E and risk of breast cancer.

BACKGROUND: Data on intake of specific carotenoids and breast cancer risk are limited. Furthermore, studies of vitamins A, C, and E in relation to breast cancer risk are inconclusive. We have conducted a large, prospective study to evaluate long-term intakes of these nutrients and breast cancer risk. METHODS: We examined, by use of multivariate analysis, associations between intakes of specific carotenoids, vitamins A, C, and E , consumption of fruits and vegetables, and breast cancer risk in a cohort of 83234 women (aged 33-60 years in 1980) who were participating in the Nurses' Health Study. Through 1994, we identified 2697 incident cases of invasive breast cancer (784 premenopausal and 1913 postmenopausal). RESULTS: Intakes of beta-carotene from food and supplements, lutein/zeaxanthin, and vitamin A from foods were weakly inversely associated with breast cancer risk in premenopausal women. Strong inverse associations were found for increasing quintiles of alpha-carotene, beta-carotene, lutein/zeaxanthin, total vitamin C from foods, and total vitamin A among premenopausal women with a positive family history of breast cancer. An inverse association was also found for increasing quintiles of beta-carotene among premenopausal women who consumed 15 g or more of alcohol per day. Premenopausal women who consumed five or more servings per day of fruits and vegetables had modestly lower risk of breast cancer than those who had less than two servings per day (relative risk [RR] = 0.77; 95% confidence interval [CI] = 0.58-1.02); this association was stronger among premenopausal women who had a positive family history of breast cancer (RR = 0.29; 95% CI = 0.13-0.62) or those who consumed 15 g or more of alcohol per day (RR = 0.53; 95% CI = 0.27-1.04). CONCLUSIONS: Consumption of fruits and vegetables high in specific carotenoids and vitamins may reduce premenopausal breast cancer risk.