Michelle D. Holmes

Plasma 25-Hydroxyvitamin D Levels and Risk of Incident Hypertension

Hydroxylation of 25(OH)D to 1,25-dihydroxyvitamin D and signaling through the vitamin D receptor occur in various tissues not traditionally involved in calcium homeostasis. Laboratory studies indicate that 1,25-dihydroxyvitamin D suppresses renin expression and vascular smooth muscle cell proliferation; clinical studies demonstrate an inverse association between ultraviolet radiation, a surrogate marker for vitamin D synthesis, and blood pressure. We prospectively studied the independent association between measured plasma 25-hydroxyvitamin D [25(OH)D] levels and risk of incident hypertension and also the association between predicted plasma 25(OH)D levels and risk of incident hypertension. Two prospective cohort studies including 613 men from the Health Professionals’ Follow-Up Study and 1198 women from the Nurses’ Health Study with measured 25(OH)D levels were followed for 4 to 8 years. In addition, 2 prospective cohort studies including 38 388 men and 77 531 women with predicted 25(OH)D levels were followed for 16 to 18 years. During 4 years of follow-up, the multivariable relative risk of incident hypertension among men whose measured plasma 25(OH)D levels were <15 ng/mL (ie, vitamin D deficiency) compared with those whose levels were ≥30 ng/mL was 6.13 (95% confidence interval [CI]: 1.00 to 37.8). Among women, the same comparison yielded a relative risk of 2.67 (95% CI: 1.05 to 6.79). The pooled relative risk combining men and women with measured 25(OH)D levels using the random-effects model was 3.18 (95% CI: 1.39 to 7.29). Using predicted 25(OH)D levels in the larger cohorts, the multivariable relative risks comparing the lowest to highest deciles were 2.31 (95% CI: 2.03 to 2.63) in men and 1.57 (95% CI: 1.44 to 1.72) in women. Plasma 25(OH)D levels are inversely associated with risk of incident hypertension.

Physical Activity and Survival After Colorectal Cancer Diagnosis

PURPOSE Physically active individuals have a lower risk of developing colorectal cancer but the influence of exercise on cancer survival is unknown. PATIENTS AND METHODS By a prospective, observational study of 573 women with stage I to III colorectal cancer, we studied colorectal cancer-specific and overall mortality according to predefined physical activity categories before and after diagnosis and by change in activity after diagnosis. To minimize bias by occult recurrences, we excluded women who died within 6 months of their postdiagnosis physical activity assessment. RESULTS Increasing levels of exercise after diagnosis of nonmetastatic colorectal cancer reduced cancer-specific mortality (P for trend = .008) and overall mortality (P for trend = .003). Compared with women who engaged in less than 3 metabolic equivalent task [MET] -hours per week of physical activity, those engaging in at least 18 MET-hours per week had an adjusted hazard ratio for colorectal cancer-specific mortality of 0.39 (95% CI, 0.18 to 0.82) and an adjusted hazard ratio for overall mortality of 0.43 (95% CI, 0.25 to 0.74). These results remained unchanged even after excluding women who died within 12 and 24 months of activity assessment. Prediagnosis physical activity was not predictive of mortality. Women who increased their activity (when comparing prediagnosis to postdiagnosis values) had a hazard ratio of 0.48 (95% CI, 0.24 to 0.97) for colorectal cancer deaths and a hazard ratio of 0.51 (95% CI, 0.30 to 0.85) for any-cause death, compared with those with no change in activity. CONCLUSION Recreational physical activity after the diagnosis of stages I to III colorectal cancer may reduce the risk of colorectal cancer-specific and overall mortality.

Non-communicable diseases in sub-Saharan Africa: what we know now

BACKGROUND Sub-Saharan Africa (SSA) has a disproportionate burden of both infectious and chronic diseases compared with other world regions. Current disease estimates for SSA are based on sparse data, but projections indicate increases in non-communicable diseases (NCDs) caused by demographic and epidemiologic transitions. We review the literature on NCDs in SSA and summarize data from the World Health Organization and International Agency for Research on Cancer on the prevalence and incidence of cardiovascular diseases, diabetes mellitus Type 2, cancer and their risk factors. METHODS We searched the PubMed database for studies on each condition, and included those that were community based, conducted in any SSA country and reported on disease or risk factor prevalence, incidence or mortality. RESULTS We found few community-based studies and some countries (such as South Africa) were over-represented. The prevalence of NCDs and risk factors varied considerably between countries, urban/rural location and other sub-populations. The prevalence of stroke ranged from 0.07 to 0.3%, diabetes mellitus from 0 to 16%, hypertension from 6 to 48%, obesity from 0.4 to 43% and current smoking from 0.4 to 71%. Hypertension prevalence was consistently similar among men and women, whereas women were more frequently obese and men were more frequently current smokers. CONCLUSIONS The prevalence of NCDs and their risk factors is high in some SSA settings. With the lack of vital statistics systems, epidemiologic studies with a variety of designs (cross-sectional, longitudinal and interventional) capable of in-depth analyses of risk factors could provide a better understanding of NCDs in SSA, and inform health-care policy to mitigate the oncoming NCD epidemic.

Dietary Factors and the Survival of Women with Breast Carcinoma

Little is known regarding how specific dietary factors affect the survival of women with breast carcinoma.

Dietary patterns and the risk of postmenopausal breast cancer.

The association between individual foods and breast cancer has been inconsistent. Therefore, we examined the association between diet and risk of postmenopausal breast cancer by the alternative approach of dietary patterns. Dietary patterns were identified with factor analysis from food consumption data collected from a food frequency questionnaire in 1984. Relative risks were computed using proportional hazard models and adjusted for known risk factors for breast cancer. Between 1984 and 2000, we ascertained 3,026 incident cases of postmenopausal breast cancer. We identified 2 major dietary patterns. The prudent pattern is characterized by higher intake of fruits, vegetables, whole grains, low‐fat dairy products, fish and poultry, while the Western pattern is characterized by higher intake of red and processed meats, refined grains, sweets and desserts and high‐fat dairy products. Neither of the patterns was associated with overall risk of postmenopausal breast cancer. However, a positive association between the Western pattern score was observed among smokers at baseline (relative risk = 1.44, comparing top to bottom quintiles; 95% CI = 1.02–2.03; p for trend = 0.03). An inverse association was observed between the prudent pattern and estrogen receptor‐negative cancer (relative risk = 0.62; 95% CI = 0.45–0.88; p for trend = 0.006). Among the major food groups, higher consumptions of fruits (relative risk for 1 serving/day increase = 0.88; 95% CI = 0.80–0.97; p = 0.009) and vegetables (relative risk = 0.94; 95% CI = 0.88–0.99; p = 0.03) were significantly associated with decreased risk for ER− breast cancer. In conclusion, we did not observe an overall association between the prudent or Western pattern and overall breast cancer risk. However, a Western‐type diet may elevate risk of breast cancer among smokers, and a prudent diet may protect against estrogen receptive‐negative tumors.

Milk consumption and acne in teenaged boys

OBJECTIVE We sought to examine the association between dietary dairy intake and teenaged acne among boys. METHODS This was a prospective cohort study. We studied 4273 boys, members of a prospective cohort study of youths and of lifestyle factors, who reported dietary intake on up to 3 food frequency questionnaires from 1996 to 1998 and teenaged acne in 1999. We computed multivariate prevalence ratios and 95% confidence intervals for acne. RESULTS After adjusting for age at baseline, height, and energy intake, the multivariate prevalence ratios (95% confidence interval; P value for test of trend) for acne comparing highest (>2 servings/d) with lowest (<1/wk) intake categories in 1996 were 1.16 (1.01, 1.34; 0.77) for total milk, 1.10 (0.94, 1.28; 0.83) for whole/2% milk, 1.17 (0.99, 1.39; 0.08) for low-fat (1%) milk, and 1.19 (1.01, 1.40; 0.02) for skim milk. LIMITATIONS Not all members of the cohort responded to the questionnaire. Acne assessment was by self-report and boys whose symptoms might have been part of an underlying disorder were not excluded. We did not adjust for steroid use and other lifestyle factors that may affect occurrence of acne. CONCLUSION We found a positive association between intake of skim milk and acne. This finding suggests that skim milk contains hormonal constituents, or factors that influence endogenous hormones, in sufficient quantities to have biological effects in consumers.

Vitamin D intake and risks of systemic lupus erythematosus and rheumatoid arthritis in women

Objectives: Vitamin D has immune-modulating effects and may protect against the development of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Methods: We identified incident cases of SLE and RA among 186 389 women followed from 1980 to 2002 in the Nurses’ Health Study and Nurses’ Health Study II cohorts. We excluded subjects where SLE or RA was not confirmed by medical record review, and those who failed to return questionnaires. Semi-quantitative food frequency questionnaires assessed vitamin D intake from food and supplements. We used cumulative-updated total energy-adjusted dietary exposures for each 2-year cycle. Relationships between vitamin D intake and incident SLE and RA were examined in age-adjusted and Cox proportional hazards models, adjusted for confounders. Results were pooled using meta-analysis random effects models. Results: We confirmed 190 incident cases of SLE and 722 of RA with dietary information. Increasing levels of vitamin D intake had no relationship to the relative risk of developing either SLE or RA. Conclusions: Vitamin D intake was not associated with risk of SLE or RA in these large prospective cohorts of women.

Body mass index before and after breast cancer diagnosis: Associations with all-cause, breast cancer, and cardiovascular disease mortality

Background: Factors related to improving outcomes in breast cancer survivors are of increasing public health significance. We examined postdiagnosis weight change in relation to mortality risk in a cohort of breast cancer survivors. Methods: We analyzed data from a cohort of 3,993 women with ages 20 to 79 years living in New Hampshire, Massachusetts, or Wisconsin with invasive nonmetastatic breast cancers diagnosed in 1988 to 1999 identified through state registries. Participants completed a structured telephone interview 1 to 2 years after diagnosis and returned a mailed follow-up questionnaire in 1998 to 2001 that addressed postdiagnosis weight and other factors. Vital status information was obtained from the National Death Index through December 2005. Hazard ratios and 95% confidence intervals were estimated from Cox proportional hazards models and adjusted for prediagnosis weight, age, stage, smoking, physical activity, and other important covariates. Results: During an average 6.3 years of follow-up from the postdiagnosis questionnaire, we identified 421 total deaths, including 121 deaths from breast cancer and 95 deaths from cardiovascular disease. Increasing postdiagnosis weight gain and weight loss were each associated with greater all-cause mortality. Among women who gained weight after breast cancer diagnosis, each 5-kg gain was associated with a 12% increase in all-cause mortality (P = 0.004), a 13% increase in breast cancer–specific mortality (P = 0.01), and a 19% increase in cardiovascular disease mortality (P = 0.04). Associations with breast cancer mortality were not modified by prediagnosis menopausal status, cigarette smoking, or body mass index. Conclusion: These findings suggest that efforts to minimize weight gain after a breast cancer diagnosis may improve survival. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1403–9)

Active and passive smoking in breast cancer: prospective results from the nurses' health study

Background. The role of active and passive smoking in breast cancer remains controversial. Methods. Using data collected in the prospective Nurses’ Health Study, we examined the influence of active and passive smoking on the incidence of invasive breast cancer. The analysis was based on women responding to the 1982 questionnaire, which included questions on passive smoking exposure. Information on active smoking was collected in biennial questionnaires. A total of 78,206 women were followed prospectively from 1982 until June 1996. Results. Of these women, 3,140 reported a diagnosis of invasive breast cancer during follow-up. Compared with never active smoking, relative risks (RR) of breast cancer were 1.04 (95% CI = 0.94–1.15) for current active smoking and 1.09 (95% CI = 1.00–1.18) for past active smoking. The RR for regular passive exposure at work and at home was 0.90 (95% CI = 0.67–1.22). For active smoking, a modest increase in risk was confined to women who began smoking before the age of 17 (RR = 1.19; 95% CI = 1.03–1.37). Conclusion. Results suggest that passive smoking is unrelated to breast cancer. However, results for active smoking are compatible with a small increase in risk when smoking is initiated at young ages.

Disparities across the breast cancer continuum

Objective: We performed a structured review of the literature to identify areas of greater and lesser knowledge of the nature of disparities across the breast cancer continuum from risk and prevention to treatment and mortality.Methods: We searched OvidMedline and PubMed to identify published studies from January 1990 to March 2004 that address disparities in breast cancer. We read the abstracts of the identified articles and then reviewed the articles if they were in English, were limited to American populations, limited to women, and described quantitative outcomes. We designated the articles as addressing one or more disparities across one or more of the domains of the breast cancer continuum.Results: Substantial research exists on racial disparities in breast cancer screening, diagnosis, treatment, and survival. Disparities in screening and treatment exist across other domains of disparities including age, insurance status, and socioeconomic position. Several gaps were identified including how factors interact.Conclusion: A structured review of breast cancer disparities suggests that research in other domains of social inequality and levels of the cancer continuum may uncover further disparities. A multidisciplinary and multi-pronged approach is needed to translate the knowledge from existing research into interventions to reduce or eliminate disparities.