Background Dietary supplements are widely used by cancer survivors. However, health effects among older cancer survivors are unclear. Methods We used the Iowa Women’s Health Study, a prospective cohort study with 2,118 postmenopausal women with a confirmed cancer diagnosis (1986–2002), to evaluate the association between postdiagnosis dietary supplement use assessed in 2004 and subsequent all-cause mortality. Risk of death was evaluated using multivariable-adjusted Cox proportional hazards regression. We performed stratified analyses by diet quality score, dietary micronutrient intake, and perceived general health. Results Through 2010, 608 deaths were identified. Approximately 85% of the cancer survivors used dietary supplements. Overall supplement use and multivitamin (MV) use were not associated with mortality. Iron supplement use was associated with 39% higher risk of death (95%CI=1.09–1.77). This association was stronger among survivors with deteriorating general health. Folic acid supplement use was associated with higher risk of death, only among survivors reporting low quality diets (HR=2.33, 95%CI=1.33–4.08, pinteraction=0.006). MV use and using a greater number of supplements was associated with a trend towards higher mortality only among those with poor diet quality. Using vitamin E supplements in combination with MV was associated with lower risk of death only among survivors with higher dietary vitamin E intake (HR=0.61, 95%CI=0.39–0.94, pinteraction=0.02). Conclusions Postdiagnosis supplement use was associated with higher mortality among older female cancer survivors with poor general health and/or poor dietary intake. Impact The association between postdiagnosis dietary supplement use and mortality may differ by diet quality and health status among older female cancer survivors.

Extensive media coverage of the potential health benefits of vitamin D supplementation has translated into substantial increases in supplement sales over recent years. Yet, the potential for drug-vitamin D interactions is rarely considered. This systematic review of the literature was conducted to evaluate the extent to which drugs affect vitamin D status or supplementation alters drug effectiveness or toxicity in humans. Electronic databases were used to identify eligible peer-reviewed studies published through September 1, 2010. Study characteristics and findings were abstracted, and quality was assessed for each study. A total of 109 unique reports met the inclusion criteria. The majority of eligible studies were classified as Class C (non-randomized trials, case-control studies, or time series) or D (cross-sectional, trend, case report/series, or before-and-after studies). Only two Class C and three Class D studies were of positive quality. Insufficient evidence was available to determine whether lipase inhibitors, antimicrobial agents, antiepileptic drugs, highly active antiretroviral agents or H2 receptor antagonists alter serum 25(OH)D concentrations. Atorvastatin appears to increase 25(OH)D concentrations, while concurrent vitamin D supplementation decreases concentrations of atorvastatin. Use of thiazide diuretics in combination with calcium and vitamin D supplements may cause hypercalcemia in the elderly, or those with compromised renal function or hyperparathyroidism. Larger studies with stronger study designs are needed to clarify potential drug-vitamin D interactions, especially for drugs metabolized by cytochrome P450 3A4 (CYP3A4). Health care providers should be aware of the potential for drug-vitamin D interactions.

Objective: To review the literature on bisphenol A (BPA) exposure and obesity in human populations. Design: Systematic review of the literature via searches of PubMed, EMBASE, Web of Science and reference lists for articles published to 1 August 2014. Setting: China, Italy, Japan, Republic of Korea, Sweden, UK, USA. Subjects: Adults (≥18 years). Results: Eighteen articles were identified and included in the review. Twelve studies included secondary evaluations of BPA exposure and BMI, and six studies evaluated body composition as the primary outcome. All analyses were crosssectional and no study included in the review received a positive quality rating (twelve negative, six neutral). Eight studies observed a statistically significant positive association between urinary or serum BPA levels and BMI, and ten studies observed no association. Studies where BMI was a primary outcome and studies of neutral quality were more likely to observe an association. Conclusions: Study results are conflicting and significant methodological issues limit the ability to draw conclusions from these studies. Prospective studies that measure BPA exposure and changes in body weight and composition are needed to establish temporality, causality and the direction of any observed associations.

Ovarian cancer is the seventh most common type of cancer in the United States and is often not diagnosed until late stages. Thus, identifying potential risk factors and prevention strategies is particularly important. This systematic review analyzes existing evidence on the association between tea consumption and epithelial ovarian cancer risk in human observational studies. PubMed was searched through September 30, 2010 for eligible articles; 16 articles met the inclusion criteria for this systematic review. Five studies found overall tea intake to be associated with a decreased epithelial ovarian cancer risk, 1 found a borderline decreased risk, 9 found no association, and 1 found a borderline increased risk. Overall, it does not appear that tea consumption increases risk of ovarian cancer, but there is insufficient evidence at this point to conclude that it is protective against ovarian cancer. Many of the studies included in this review had important limitations, especially related to the lack of detailed data collected on tea consumption. Further research is needed and should focus on more detailed assessment of type of tea consumed, frequency, and duration of tea intake. Future studies should also explore potential differences in the association between tea intake and ovarian cancer risk among subpopulations.

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The enzymes folylpolyglutamate synthase (FPGS) and gamma-glutamyl hydrolase (GGH) are essential for determining intracellular folate availability for one-carbon metabolism (OCM) pathways. FPGS adds glutamyl groups to the folate molecule, thereby converting folate into the preferred substrate for several enzymes in OCM pathways. GGH removes glutamyl groups, allowing folate metabolites to leave the cell. The purpose of this study was to evaluate whether single nucleotide polymorphisms (SNPs) in the FPGS and GGH genes influence measured plasma homocysteine levels. Study participants were a sub-cohort (n = 482) from the Singapore Chinese Health Study. SNPs were selected using HapMap tagSNPs and SNPs previously reported in the scientific literature. Multiple linear regression was used to evaluate the association between individual SNPs and plasma homocysteine levels. Two FPGS (rs10106, rs1098774) and 9 GGH (rs719235, rs1031552, rs1800909, rs3758149, rs3780126, rs3824333, rs4617146, rs11545076, rs11545078) SNPs were included in the final analysis. Neither of the FPGS SNPs, but three GGH SNPs were associated with plasma homocysteine levels: rs11545076 (p=0.001), rs1800909 (p=0.02), and rs3758149 (p = 0.006). Only one (rs11545076) remained statistically significant after adjusting for multiple comparisons. This study suggests that GGH SNPs, rs11545076, rs1800909, and rs3758149, may have functional relevance and result in alterations in plasma homocysteine levels. Since this is one of the first studies to assess FPGS and GGH genetic variants in relation to plasma homocysteine, further research is needed to confirm these findings and characterize the functional effects of these variants.

Taller height, family history of breast and ovarian cancer, younger age at menarche, and older age at menopause are non-modifiable breast cancer risk factors. In previous studies, adherence to the 2007 World Cancer Research Fund (WCRF)/ American Institute for Cancer Research (AICR) diet and physical activity recommendations were associated with lower cancer risk. We hypothesized that guideline adherence would be associated with lower breast cancer risk, and that the recommendations might be more beneficial among women with non-modifiable risk factors. This analysis included data from 36,626 postmenopausal women in the Iowa Women's Health Study with no history of cancer at baseline. Data from the 1986 baseline questionnaire were used to create scores for the WCRF/AICR recommendations for BMI, physical activity, and intake of fruits and vegetables, fiber, alcohol, red and processed meat, sugary beverages and sodium. One point was assigned for complete adherence, 0.5 points for partial adherence and 0 points for non-adherence. Points were summed to create an overall adherence score (max. = 8). Multivariate-adjusted Cox regression was used to evaluate associations between the overall score and single recommendation adherence with breast cancer risk (n = 3189, baseline - 2010). Stratified analyses were used to evaluate whether associations differed by height (<66 in./≥66 in.), family history of breast or ovarian cancer (yes/no), and ages at menarche (quartiles) and menopause (quartiles). The mean adherence score was 5.0 (range: 0.5 - 8.0). Overall, a higher score was associated with a lower breast cancer risk (HR: 0.94, 95% CI: 0.91-0.97). Alcohol intake (HR: 0.81, 95% CI: 0.70 - 0.94) and BMI (HR: 0.79, 95% CI: 0.72 - 0.87) were the only specific recommendations significantly associated with breast cancer risk. The association between adherence score and breast cancer risk did not differ significantly across strata for any of the non-modifiable risk factors. Alcohol intake was more strongly associated with breast cancer risk in taller women (HR: 0.72, 95% CI: 0.55 - 0.93 vs. HR: 0.85, 95% CI: 0.71 - 1.03 for shorter women; pinteraction = 0.46), while a stronger association with BMI was observed in shorter women (HR: 0.75, 95% CI: 0.67 - 0.84 vs. HR: 0.86, 95% CI: 0.86 - 1.01 for taller women; pinteraction = 0.12). High physical activity was associated with lower breast cancer risk in women who where younger at menarche (HR: 0.77, 95% CI: 0.61 - 0.97 vs. HR: 1.05, 95% CI: 0.88 - 1.25 for older age at menarche; pinteraction = 0.01). Alcohol intake <10g/day and maintaining a BMI between 18.5 - 25 were most strongly associated with lower breast cancer risk among all women. The results suggest women with non-modifiable risk factors may not receive additional benefit, but that limiting alcohol intake, maintaining a healthy BMI and regular physical activity may be important recommendations for these women. Citation Format: Sarah Oppeneer, Maki Inoue-Choi, DeAnn Lazovich, Kim Robien. WCRF/AICR recommendation adherence and breast cancer incidence among postmenopausal women with non-modifiable risk factors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 146. doi:10.1158/1538-7445.AM2013-146