James M. Shikany

Calcium Plus Vitamin D Supplementation and the Risk of Breast Cancer

BACKGROUND Although some observational studies have associated higher calcium intake and especially higher vitamin D intake and 25-hydroxyvitamin D levels with lower breast cancer risk, no randomized trial has evaluated these relationships. METHODS Postmenopausal women (N = 36 282) who were enrolled in a Womens Health Initiative clinical trial were randomly assigned to 1000 mg of elemental calcium with 400 IU of vitamin D(3) daily or placebo for a mean of 7.0 years to determine the effects of supplement use on incidence of hip fracture. Mammograms and breast exams were serially conducted. Invasive breast cancer was a secondary outcome. Baseline serum 25-hydroxyvitamin D levels were assessed in a nested case-control study of 1067 case patients and 1067 control subjects. A Cox proportional hazards model was used to estimate the risk of breast cancer associated with random assignment to calcium with vitamin D(3). Associations between 25-hydroxyvitamin D serum levels and total vitamin D intake, body mass index (BMI), recreational physical activity, and breast cancer risks were evaluated using logistic regression models. Statistical tests were two-sided. RESULTS Invasive breast cancer incidence was similar in the two groups (528 supplement vs 546 placebo; hazard ratio = 0.96; 95% confidence interval = 0.85 to 1.09). In the nested case-control study, no effect of supplement group assignment on breast cancer risk was seen. Baseline 25-hydroxyvitamin D levels were modestly correlated with total vitamin D intake (diet and supplements) (r = 0.19, P < .001) and were higher among women with lower BMI and higher recreational physical activity (both P < .001). Baseline 25-hydroxyvitamin D levels were not associated with breast cancer risk in analyses that were adjusted for BMI and physical activity (P(trend) = .20). CONCLUSIONS Calcium and vitamin D supplementation did not reduce invasive breast cancer incidence in postmenopausal women. In addition, 25-hydroxyvitamin D levels were not associated with subsequent breast cancer risk. These findings do not support a relationship between total vitamin D intake and 25-hydroxyvitamin D levels with breast cancer risk.

Serum Vitamin D Concentration and Prostate Cancer Risk: A Nested Case - Control Study

BACKGROUND Epidemiological studies have yielded inconsistent associations between vitamin D status and prostate cancer risk, and few studies have evaluated whether the associations vary by disease aggressiveness. We investigated the association between vitamin D status, as determined by serum 25-hydroxyvitamin D [25(OH)D] level, and risk of prostate cancer in a case-control study nested within the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. METHODS The study included 749 case patients with incident prostate cancer who were diagnosed 1-8 years after blood draw and 781 control subjects who were frequency matched by age at cohort entry, time since initial screening, and calendar year of cohort entry. All study participants were selected from the trial screening arm (which includes annual standardized prostate cancer screening). Conditional logistic regression was used to estimate adjusted odds ratios (ORs) with 95% confidence intervals (CIs) by quintile of season-standardized serum 25(OH)D concentration. Statistical tests were two-sided. RESULTS No statistically significant trend in overall prostate cancer risk was observed with increasing season-standardized serum 25(OH)D level. However, serum 25(OH)D concentrations greater than the lowest quintile (Q1) were associated with increased risk of aggressive (Gleason sum > or = 7 or clinical stage III or IV) disease (in a model adjusting for matching factors, study center, and history of diabetes, ORs for Q2 vs Q1 = 1.20, 95% CI = 0.80 to 1.81, for Q3 vs Q1 =1.96, 95% CI = 1.34 to 2.87, for Q4 vs Q1 = 1.61, 95% CI = 1.09 to 2.38, and for Q5 vs Q1 = 1.37, 95% CI = 0.92 to 2.05; P(trend) = .05). The rates of aggressive prostate cancer for increasing quintiles of serum 25(OH)D were 406, 479, 780, 633, and 544 per 100 000 person-years. In exploratory analyses, these associations with aggressive disease were consistent across subgroups defined by age, family history of prostate cancer, diabetes, body mass index, vigorous physical activity, calcium intake, study center, season of blood collection, and assay batch. CONCLUSION The findings of this large prospective study do not support the hypothesis that vitamin D is associated with decreased risk of prostate cancer; indeed, higher circulating 25(OH)D concentrations may be associated with increased risk of aggressive disease.

Obesity and Thyroid Cancer Risk among U.S. Men and Women: A Pooled Analysis of Five Prospective Studies

Background: Thyroid cancer incidence has risen dramatically in the United States since the early 1980s. Although the prevalence of obesity has doubled during this time period, the relationship between obesity and thyroid cancer is uncertain. Methods: We examined the association between body mass index (BMI) and thyroid cancer risk in a pooled analysis of five prospective U.S. studies, including 413,979 women and 434,953 men. Proportional hazards models with attained age as the time metric were adjusted for education, race, marital status, smoking, alcohol intake, and (where appropriate) cohort and sex. Results: Over follow-up (mean = 10.3 years), 768 women and 388 men were diagnosed with thyroid cancer. The risk of thyroid cancer was greater with increasing BMI [per 5 kg/m2: HR in women, 1.16 (95% CI, 1.08–1.24); HR in men, 1.21 (95% CI, 0.97–1.49)]. There was no significant heterogeneity between studies (both P > 0.05). For women and men combined, the HRs for overweight (25.0–29.9 kg/m2) and obesity (≥30 kg/m2) compared with normal-weight (18.5–24.9 kg/m2) were 1.20 (95% CI, 1.04–1.38) and 1.53 (95% CI, 1.31–1.79), respectively. We found no significant effect modification by other factors, and the results did not differ significantly by histologic type. A significant positive association for BMI in young adulthood (ages 18–20) with thyroid cancer risk was also observed [per 5-kg/m2 increase: HR, 1.18 (95% CI, 1.03–1.35)]. Conclusion: BMI was positively associated with thyroid cancer risk in both men and women. Impact: Our study provides strong evidence that obesity is an independent risk factor for thyroid cancer. Cancer Epidemiol Biomarkers Prev; 20(3); 464–72. ©2011 AACR.

Multivitamin use and risk of cancer and cardiovascular disease in the women's health initiative cohorts

BACKGROUND Millions of postmenopausal women use multivitamins, often believing that supplements prevent chronic diseases such as cancer and cardiovascular disease (CVD). Therefore, we decided to examine associations between multivitamin use and risk of cancer, CVD, and mortality in postmenopausal women. METHODS The study included 161 808 participants from the Womens Health Initiative clinical trials (N = 68 132 in 3 overlapping trials of hormone therapy, dietary modification, and calcium and vitamin D supplements) or an observational study (N = 93 676). Detailed data were collected on multivitamin use at baseline and follow-up time points. Study enrollment occurred between 1993 and 1998; the women were followed up for a median of 8.0 years in the clinical trials and 7.9 years in the observational study. Disease end points were collected through 2005. We documented cancers of the breast (invasive), colon/rectum, endometrium, kidney, bladder, stomach, ovary, and lung; CVD (myocardial infarction, stroke, and venous thromboembolism); and total mortality. RESULTS A total of 41.5% of the participants used multivitamins. After a median of 8.0 years of follow-up in the clinical trial cohort and 7.9 years in the observational study cohort, 9619 cases of breast, colorectal, endometrial, renal, bladder, stomach, lung, or ovarian cancer; 8751 CVD events; and 9865 deaths were reported. Multivariate-adjusted analyses revealed no association of multivitamin use with risk of cancer (hazard ratio [HR], 0.98, and 95% confidence interval [CI], 0.91-1.05 for breast cancer; HR, 0.99, and 95% CI, 0.88-1.11 for colorectal cancer; HR, 1.05, and 95% CI, 0.90-1.21 for endometrial cancer; HR, 1.0, and 95% CI, 0.88-1.13 for lung cancer; and HR, 1.07, and 95% CI, 0.88-1.29 for ovarian cancer); CVD (HR, 0.96, and 95% CI, 0.89-1.03 for myocardial infarction; HR, 0.99, and 95% CI, 0.91-1.07 for stroke; and HR, 1.05, and 95% CI, 0.85-1.29 for venous thromboembolism); or mortality (HR, 1.02, and 95% CI, 0.97-1.07). CONCLUSION After a median follow-up of 8.0 and 7.9 years in the clinical trial and observational study cohorts, respectively, the Womens Health Initiative study provided convincing evidence that multivitamin use has little or no influence on the risk of common cancers, CVD, or total mortality in postmenopausal women.

25-Hydroxyvitamin D levels and cognitive performance and decline in elderly men

Objective: To test the hypothesis that lower 25-hydroxyvitamin D [25(OH)D] levels are associated with a greater likelihood of cognitive impairment and risk of cognitive decline. Methods: We measured 25(OH)D and assessed cognitive function using the Modified Mini-Mental State Examination (3MS) and Trail Making Test Part B (Trails B) in a cohort of 1,604 men enrolled in the Osteoporotic Fractures in Men Study and followed them for an average of 4.6 years for changes in cognitive function. Results: In a model adjusted for age, season, and site, men with lower 25(OH)D levels seemed to have a higher odds of cognitive impairment, but the test for trend did not reach significance (impairment by 3MS: odds ratio [OR] 1.84, 95% confidence interval [CI] 0.81–4.19 for quartile [Q] 1; 1.41, 0.61–3.28 for Q2; and 1.18, 0.50–2.81 for Q3, compared with Q4 [referent group; p trend = 0.12]; and impairment by Trails B: OR 1.66, 95% CI 0.98–2.82 for Q1; 0.96, 0.54–1.69 for Q2; and 1.30, 0.76–2.22 for Q3, compared with Q4 [p trend = 0.12]). Adjustment for age and education further attenuated the relationships. There was a trend for an independent association between lower 25(OH)D levels and odds of cognitive decline by 3MS performance (multivariable OR 1.41, 95% CI 0.89–2.23 for Q1; 1.28, 0.84–1.95 for Q2; and 1.06, 0.70–1.62 for Q3, compared with Q4 [p = 0.10]), but no association with cognitive decline by Trails B. Conclusion: We found little evidence of independent associations between lower 25-hydroxyvitamin D level and baseline global and executive cognitive function or incident cognitive decline.

Association of Race and Sex With Risk of Incident Acute Coronary Heart Disease Events

CONTEXT It is unknown whether long-standing disparities in incidence of coronary heart disease (CHD) among US blacks and whites persist. OBJECTIVE To examine incident CHD by black and white race and by sex. DESIGN, SETTING, AND PARTICIPANTS Prospective cohort study of 24,443 participants without CHD at baseline from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, who resided in the continental United States and were enrolled between 2003 and 2007 with follow-up through December 31, 2009. MAIN OUTCOME MEASURE Expert-adjudicated total (fatal and nonfatal) CHD, fatal CHD, and nonfatal CHD (definite or probable myocardial infarction [MI]; very small non-ST-elevation MI [NSTEMI] had peak troponin level <0.5 μg/L). RESULTS Over a mean (SD) of 4.2 (1.5) years of follow-up, 659 incident CHD events occurred (153 in black men, 138 in black women, 254 in white men, and 114 in white women). Among men, the age-standardized incidence rate per 1000 person-years for total CHD was 9.0 (95% CI, 7.5-10.8) for blacks vs 8.1 (95% CI, 6.9-9.4) for whites; fatal CHD: 4.0 (95% CI, 2.9-5.3) vs 1.9 (95% CI, 1.4-2.6), respectively; and nonfatal CHD: 4.9 (95% CI, 3.8-6.2) vs 6.2 (95% CI, 5.2-7.4). Among women, the age-standardized incidence rate per 1000 person-years for total CHD was 5.0 (95% CI, 4.2-6.1) for blacks vs 3.4 (95% CI, 2.8-4.2) for whites; fatal CHD: 2.0 (95% CI, 1.5-2.7) vs 1.0 (95% CI, 0.7-1.5), respectively; and nonfatal CHD: 2.8 (95% CI, 2.2-3.7) vs 2.2 (95% CI, 1.7-2.9). Age- and region-adjusted hazard ratios for fatal CHD among blacks vs whites was near 2.0 for both men and women and became statistically nonsignificant after multivariable adjustment. The multivariable-adjusted hazard ratio for incident nonfatal CHD for blacks vs whites was 0.68 (95% CI, 0.51-0.91) for men and 0.81 (95% CI, 0.58-1.15) for women. Of the 444 nonfatal CHD events, 139 participants (31.3%) had very small NSTEMIs. CONCLUSIONS The higher risk of fatal CHD among blacks compared with whites was associated with cardiovascular disease risk factor burden. These relationships may differ by sex.

Food price and diet and health outcomes: 20 years of the CARDIA Study.

BACKGROUND Despite surging interest in taxation as a policy to address poor food choice, US research directly examining the association of food prices with individual intake is scarce. METHODS This 20-year longitudinal study included 12 123 respondent days from 5115 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Associations between food price, dietary intake, overall energy intake, weight, and homeostatic model assessment insulin resistance (HOMA-IR) scores were assessed using conditional log-log and linear regression models. RESULTS The real price (inflated to 2006 US dollars) of soda and pizza decreased over time; the price of whole milk increased. A 10% increase in the price of soda or pizza was associated with a -7.12% (95% confidence interval [CI], -63.50 to -10.71) or -11.5% (95% CI, -17.50 to -5.50) change in energy from these foods, respectively. A

Predictors of Non-Spine Fracture in Elderly Men: The MrOS Study†

1.00 increase in soda price was also associated with lower daily energy intake (-124 [95% CI, -198 to -50] kcal), lower weight (-1.05 [95% CI, -1.80 to -0.31] kg), and lower HOMA-IR score (0.42 [95% CI, -0.60 to -0.23]); similar trends were observed for pizza. A

Vitamin D deficiency in older men.

1.00 increase in the price of both soda and pizza was associated with greater changes in total energy intake (-181.49 [95% CI, -247.79 to -115.18] kcal), body weight (-1.65 [95% CI, -2.34 to 0.96] kg), and HOMA-IR (-0.45 [95% CI, -0.59 to -0.31]). CONCLUSION Policies aimed at altering the price of soda or away-from-home pizza may be effective mechanisms to steer US adults toward a more healthful diet and help reduce long-term weight gain or insulin levels over time.

Will reducing sugar‐sweetened beverage consumption reduce obesity? Evidence supporting conjecture is strong, but evidence when testing effect is weak

We examined determinants of nonvertebral fracture in elderly men from six U.S. communities followed an average of 4.1 years. Six clinical risk factors predicted fracture risk independent of hip BMD: tricyclic antidepressant use, previous fracture, inability to complete a narrow walk trial, falls in previous year, age ≥80 years, and depressed mood.