Occupational exposure to arsenic and risk of nonmelanoma skin cancer in a multinational European study

Occupational studies show a high risk of lung cancer related to arsenic exposure by inhalation; however, only a few studies, and with conflicting results, previously examined a potential link between arsenic exposure at work and skin cancer. The aim of this study is to assess airborne arsenic exposures at the workplace and to quantify associations with nonmelanoma skin cancer (NMSC). The study sample consists of 618 incident cases of NMSC and 527 hospital‐based controls aged 30–79 years from Hungary, Romania and Slovakia. Exposures were evaluated by local experts using occupational histories. Information on host factors and other exposures was collected and used to adjust the associations of interest using multivariable logistic regression. The lifetime prevalence of exposure to work‐related arsenic is 23.9% for cases and 15.5% for controls. No significant association between arsenic exposure in the workplace and NMSC was detected, although an increased adjusted odd ratio was observed for participants with higher cumulative lifetime workplace exposure to arsenic in dust and fumes compared to referents [odds ratios (OR) = 1.94, 95% confidence interval (CI) = 0.76–4.95]. There is evidence for modification of the workplace arsenic–NMSC association by work‐related sunlight exposure in women, with a markedly increased adjusted OR in the presence of workplace sunlight exposure (OR = 10.22, 95% CI = 2.48–42.07). Workplace coexposure to arsenic and sunlight may thus pose an increased risk of NMSC.     

Niacin intake and risk of skin cancer in US women and men

A recent clinical trial found a protective role of niacinamide, a derivative of niacin, against skin cancer recurrence. However, there is no epidemiologic study to assess the association between niacin intake and risk of skin cancer [basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and melanoma]. We prospectively evaluated whether total, dietary and supplemental niacin intake was associated with skin cancer risk based on 72,308 women in the Nurses' Health Study (1984–2010) and 41,808 men in the Health Professionals Follow‐up Study (1986–2010). Niacin intake was assessed every 2 to 4 years during follow‐up and cumulative averaged intake. Cox proportional hazard models were used to compute the hazard ratios (HR) and 95% confidence intervals (CI) and cohort‐specific results were pooled using a random‐effects model. During the follow‐up, we documented 23,256 BCC, 2,530 SCC and 887 melanoma cases. Total niacin intake was inversely associated with SCC risk; the pooled HR for top vs. bottom quintiles was 0.84 (95% CI = 0.74–0.95; p_trend = 0.08). However, there were a marginally positive association between total niacin intake and BCC risk; the pooled HR for top versus bottom quintiles was 1.05 (95% CI = 1.01–1.10; p_trend < 0.01). Higher total niacin intake was also marginally positively associated with melanoma risk in men, but not in women. The results were similar in stratified analyses according to sun exposure related factors and by body location of melanoma and SCC. Our study supports a potential beneficial role of niacin intake in relation to SCC but not of BCC or melanoma.     

Dietary nitrate and nitrite intake and risk of colorectal cancer in the Shanghai Women's Health Study

Nitrate and nitrite are precursors of endogenously formed N‐nitroso compounds (NOC), known animal carcinogens. Nitrosation reactions forming NOCs can be inhibited by vitamin C and other antioxidants. We prospectively investigated the association between dietary nitrate and nitrite intake and risk of colorectal cancer in the Shanghai Women's Health Study, a cohort of 73,118 women ages 40–70 residing in Shanghai. We evaluated effect modification by factors that affect endogenous formation of NOCs: vitamin C (at or above/below median) and red meat intake (at or above/below median). Nitrate, nitrite and other dietary intakes were estimated from a 77‐item food frequency questionnaire administered at baseline. Over a mean of 11 years of follow‐up, we identified 619 colorectal cancer cases (n = 383, colon; n = 236, rectum). Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazard regression. Overall, nitrate intake was not associated with colorectal cancer risk (HR = 1.08; 95% CI: 0.73–1.59). However, among women with vitamin C intake below the median (83.9 mg day^?1) and hence higher potential exposure to NOCs, risk of colorectal cancer increased with increasing quintiles of nitrate intake (highest vs. lowest quintile HR = 2.45; 95% CI: 1.15–5.18; p trend = 0.02). There was no association among women with higher vitamin C intake. We found no association between nitrite intake and risk of colorectal cancer overall or by intake level of vitamin C. Our findings suggest that high dietary nitrate intake among subgroups expected to have higher exposure to endogenously formed NOCs increases risk of colorectal cancer.     

Dietary calcium, vitamin D, VDR genotypes and colorectal cancer

The vitamin D receptor (VDR) may importantly modulate risk of colorectal cancer either independently or in conjunction with calcium and vitamin D intake. We evaluate the association between calcium, vitamin D, dairy products, and VDR polymorphisms in 2 case-control studies of colon and rectal cancer (n = 2,306 cases and 2,749 controls). Dietary intake was evaluated using a detailed diet history questionnaire. Two VDR polymorphisms were evaluated: an intron 8 Bsm 1 polymorphism and a 3' untranslated region poly-A length polymorphism (designated S for short and L for long). The SS genotype reduced risk of colorectal cancer for men (odds ratio [OR] = 0.71; 95% confidence interval [CI] = 0.55-0.92). High levels of calcium intake reduced risk of rectal cancer in women (OR = 0.39; 95% CI = 0.24-0.64) but were not associated with rectal cancer in men (OR = 1.02; 95% CI = 0.66-1.56). Similar reduced rectal cancer risk among women was observed at high levels of vitamin D (OR = 0.52; 95% CI = 0.32-0.85) and low-fat dairy products (OR = 0.61; 95% CI = 0.39-0.94). High levels of sunshine exposure reduced risk of rectal cancer among those diagnosed when <60 years of age (OR = 0.62, 95% CI = 0.42-0.93). Examination of calcium in conjunction with VDR genotype showed that a significant 40% reduction in risk of rectal cancer was observed for the SS or BB VDR genotypes when calcium intake was low (p interaction = 0.01 for calcium interaction). For colon cancer, high levels of dietary intake of calcium, vitamin D, and low-fat dairy products reduced risk of cancer for the SS or BB VDR genotypes, although the p for interaction was not statistically significant. These data support previous observations that high levels of calcium and vitamin D reduce risk of rectal cancer and provide support for a weak protective effect for the SS and BB VDR genotypes. The risk associated with VDR genotype seems to depend upon the level of dietary calcium and vitamin D and tumor site.     

Vitamin D intake and breast cancer risk in postmenopausal women: the Iowa Women’s Health Study

Vitamin D, a prosteroid hormone with anti-proliferative and pro-differentiation activity, is thought to act as a cancer chemopreventive agent. This study evaluated the association between vitamin D intake and breast cancer risk among women in a large prospective cohort study. A total of 34,321 postmenopausal women who had completed a questionnaire that included diet and supplement use were followed for breast cancer incidence from 1986 to 2004. Adjusted relative risks (RR) for breast cancer were calculated for dietary, supplemental, and total vitamin D intake among all women. The adjusted RR of breast cancer for women consuming >800 IU/day versus <400 IU/day total vitamin D was 0.89 (95% CI: 0.77–1.03). RRs were stronger among women with negative than positive ER or PR status. The association of high vitamin D intake with breast cancer was strongest in the first 5 years after baseline dietary assessment (RR = 0.66; 95% CI: 0.46–0.94 compared with lowest-intake group), and diminished over time. Changes in vitamin D intake over time might have contributed to the diminished association observed in later years. Vitamin D intake of >800 IU/day appears to be associated with a small decrease in risk of breast cancer among postmenopausal women. Studies evaluating all sources of vitamin D, especially sun exposure, are needed to fully understand the association between vitamin D and breast cancer risk.     

Association between dietary antioxidant vitamins intake/blood level and risk of gastric cancer

We aimed to systematically evaluate the association between dietary intake/blood levels of antioxidant vitamins (vitamin C, vitamin E, β‐carotene, and α‐carotene) and gastric cancer risk. Systematic literature searches were conducted until April 2013 in Pubmed and Embase to identify relevant studies. Either a fixed‐ or a random‐effects model was adopted to estimate overall odds ratios (ORs). Dose–response, meta‐regression, subgroup, and publication bias analyses were applied. Forty articles were finally included in the present study. Higher dietary intake of vitamin C, vitamin E, β‐carotene, and α‐carotene was inversely associated with gastric cancer risk (for vitamin C, pooled OR = 0.58, 95% CI 0.51–0.65; for vitamin E, pooled OR = 0.65, 95% CI 0.57–0.74; for β‐carotene, pooled OR = 0.59, 95% CI 0.49–0.70; for α‐carotene, pooled OR = 0.69, 95% CI 0.52–0.93). Subgroup analyses suggested the effects of these antioxidant vitamins were different in gastric cancer subtypes. As indicated by dose–response analysis, a 100 mg/day increment of vitamin C intake conferred an OR of 0.78 (95% CI 0.67–0.90); a 15 mg/day increment of vitamin E intake conferred an OR of 0.79 (95% CI 0.66–0.94); and a 5 mg/day increment in β‐carotene intake conferred an OR of 0.80 (95% CI 0.60–1.04). No significant association was observed between blood vitamin C, α‐tocopherol, γ‐ tocopherol, β‐carotene and α‐carotene levels and gastric cancer risk. In conclusion, dietary intake of vitamin C, vitamin E, β‐carotene and α‐carotene was inversely associated with gastric cancer risk while no such association was observed for blood levels of these antioxidant vitamins, thus the results should be interpreted cautiously.     

Breast cancer in postmenopausal women after non-melanomatous skin cancer: the Women’s Health Initiative observational study

An increased risk of breast cancer has been reported in patients with non-melanomatous skin cancer (NMSC), but this association has not been studied in a large, multi-geographic population. We utilized data from the Women’s Health Initiative observational study to assess whether history of NMSC is associated with breast cancer risk. This analysis included 70,246 postmenopausal White and Hispanic women aged 50–79, in which 4,247 breast cancer cases were identified over a mean (SD) of 11.3 (3.2) years. Baseline information was collected on demographics, medical history, sun exposure, and vitamin D intake. Cox proportional hazards regression was used to calculate hazard ratios (HRs) with 95 % confidence intervals (CIs). The relationship between NMSC and breast cancer was examined as a time-dependent exposure using updated information on NMSC gathered during follow-up visits. All statistical tests were two sided. There were 5,595 women diagnosed with NMSC at study entry. The annualized rate of breast cancer was 0.64 % among women with a history of NMSC and 0.55 % among women with no history of NMSC. The multivariable-adjusted HR for breast cancer among women with a history of NMSC versus no history of NMSC was 1.07 (95 % CI 0.95–1.20, P = 0.27). Further evaluation stratified by tumor characteristics showed an increased risk of lymph node-positive disease, HR = 1.30 (95 % CI 1.01–1.67, P = 0.04), and regional-stage disease, HR = 1.33 (95 % CI 1.05–1.70, P = 0.02), among women with NMSC. There was no significant overall association between NMSC and breast cancer; however, there was an increased risk of more advanced-stage breast cancer which needs further exploration.     

Vitamin C and survival among women with breast cancer: A Meta-analysis

BackgroundThe association between dietary vitamin C intake and breast cancer survival is inconsistent and few studies have specifically examined vitamin C supplement use among women with breast cancer. The purpose of this study was to summarise results from prospective studies on the association between vitamin C supplement use and dietary vitamin C intake and breast cancer-specific mortality and total mortality.MethodsStudies were identified using the PubMed database through February 6, 2014 and by examining the references of retrieved articles. Prospective studies were included if they reported relative risks (RR) with 95% confidence intervals (95% CIs) for at least two categories or as a continuous exposure. Random-effects models were used to combine study-specific results.ResultsThe ten identified studies examined vitamin C supplement use (n = 6) and dietary vitamin C intake (n = 7) and included 17,696 breast cancer cases, 2791 total deaths, and 1558 breast cancer-specific deaths. The summary RR (95% CI) for post-diagnosis vitamin C supplement use was 0.81 (95% CI 0.72–0.91) for total mortality and 0.85 (95% CI 0.74–0.99) for breast cancer-specific mortality. The summary RR for a 100 mg per day increase in dietary vitamin C intake was 0.73 (95% CI 0.59–0.89) for total mortality and 0.78 (95% CI 0.64–0.94) for breast cancer-specific mortality.ConclusionResults from this meta-analysis suggest that post-diagnosis vitamin C supplement use may be associated with a reduced risk of mortality. Dietary vitamin C intake was also statistically significantly associated with a reduced risk of total mortality and breast cancer-specific mortality.     

Sun Exposure Makes no Discrimination based on Vitamin D Status and VDR-Foki Polymorphisms for Non-Melanoma Skin Cancers Risk in Iranian Subjects: A Case-Control Study

Background and Objective: Sunlight exposure, the main source of endogenous vitamin D synthesis, may increase the risk of non-melanoma skin cancers (NMSC) development. Vitamin D receptor (VDR) polymorphisms are associated with various malignancies. This study aimed to examine the associations between vitamin D status and VDR FokI polymorphisms in Iranian subjects with NMSC. Materials and Methods: This case-control study included 73 diagnosed cases of NMSC and 72 healthy controls from dermatology clinics at Razi Hospital, Tehran, Iran. A questionnaire was used to assess sunlight exposure. The extracted DNA from whole blood samples was genotyped and serum concentrations of 25-hydroxycalciferol (25(OH)D)) and intact parathyroid hormone (iPTH) were measured. Results: We found a significant higher duration of cumulative sunlight exposure in cases compared with controls (p<0.001). However, 25(OH)D and iPTH concentrations were not significantly different between cases and controls (30±15 vs. 29±15 ng/mL, p=0.78 and 46.0±20 vs. 40.5±23 pg/mL, p=0.14, respectively). We did not observe any significant increased risk of NMSC due to f allele, as compared with FF (OR =2.33, 95% CI 0.81-6.75, p=0.12). Conclusion: Though sunlight exposure was associated with increased NMSC risk, there were no significant associations between vitamin D status or VDR FokI polymorphisms with NMSC development in our subjects.     

Dietary vitamin D and cancers of the oral cavity and esophagus

BackgroundData on the association between vitamin D and upper digestive tract neoplasms are limited.MethodsIn two case–control studies in Italy, we examined the relation between dietary vitamin D intake and squamous cell carcinoma of the esophagus (SCCE; 304 cases) and oral/pharyngeal cancer (804 cases). Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by multiple logistic regression.ResultsAdjusted ORs for SCCE and oral/pharyngeal cancer were 0.58 (95% CI 0.39–0.86) and 0.76 (95% CI 0.60–0.94), respectively, for the highest tertile of vitamin D intake. Using a reference group of those in the highest tertile of vitamin D who were never/former smokers, ORs were 8.7 (95% CI 4.1–18.7) for SCCE and 10.4 (95% CI 6.9–15.5) for oral/pharyngeal cancer among heavy smokers in the lowest vitamin D tertile; similarly, compared with those in the highest tertile of vitamin D who drank <3 alcoholic drinks/day, corresponding ORs were 41.9 (95% CI 13.7–128.6) for SCCE and 8.5 (95% CI 5.7–12.5) for oral/pharyngeal cancer, among heavy alcohol drinkers in the lowest vitamin D tertile.ConclusionWe observed inverse associations between dietary vitamin D intake and risk of SCCE and, perhaps, oral/pharyngeal cancer, which were most pronounced among heavy current smokers and heavy consumers of alcohol.     

Vitamin D and pancreatic cancer: a pooled analysis from the Pancreatic Cancer Case–Control Consortium

BackgroundThe potential role of vitamin D in the aetiology of pancreatic cancer is unclear, with recent studies suggesting both positive and negative associations.Patients and methodsWe used data from nine case–control studies from the International Pancreatic Cancer Case–Control Consortium (PanC4) to examine associations between pancreatic cancer risk and dietary vitamin D intake. Study-specific odds ratios (ORs) were estimated using multivariable logistic regression, and ORs were then pooled using a random-effects model. From a subset of four studies, we also calculated pooled estimates of association for supplementary and total vitamin D intake.ResultsRisk of pancreatic cancer increased with dietary intake of vitamin D [per 100 international units (IU)/day: OR = 1.13, 95% confidence interval (CI) 1.07–1.19, P = 7.4 × 10^-6, P-heterogeneity = 0.52; ≥230 versus <110 IU/day: OR = 1.31, 95% CI 1.10–1.55, P = 2.4 × 10^-3, P-heterogeneity = 0.81], with the association possibly stronger in people with low retinol/vitamin A intake.ConclusionIncreased risk of pancreatic cancer was observed with higher levels of dietary vitamin D intake. Additional studies are required to determine whether or not our finding has a causal basis.     

Calcium, dairy foods, vitamin D, and colorectal cancer risk: the Fukuoka Colorectal Cancer Study

Epidemiologic evidence supporting a protective role of calcium and vitamin D in colorectal carcinogenesis has been accumulating in Western populations, but it is limited in Asian populations, whose intake of calcium is relatively low. We investigated the association of intakes of these nutrients with colorectal cancer risk in Japanese. Study subjects were participants of a large-scale case-control study in Fukuoka, Japan. Diet was assessed through interview regarding 148 dietary items by showing typical foods or dishes on the display of a personal computer. In a multivariate analysis adjusting for potential confounding variables, calcium intake was significantly, inversely associated with colorectal cancer risk (P for trend=0.01); the odds ratio for the highest versus lowest quintile of calcium intake was 0.64 (95% confidence interval, 0.45-0.93). Higher levels of dietary vitamin D were significantly associated with decreased risk of colorectal cancer among those who had fewer chances of sunlight exposure at work or in leisure (P for trend=0.02). A decreased risk of colorectal cancer associated with high calcium intake was observed among those who had higher levels of vitamin D intake or among those who had a greater chance of daily sunlight exposure, but not among those with medium or lower intake of vitamin D or among those with potentially decreased sunlight exposure. These results add to support for a joint action of calcium and vitamin D in the prevention of colorectal carcinogenesis.     

Dairy foods and nutrients in relation to risk of ovarian cancer and major histological subtypes

Inconsistent results for the role of dairy food intake in relation to ovarian cancer risk may reflect the potential adverse effects of lactose, which has been hypothesized to increase gonadotropin levels, and the beneficial antiproliferative effects of calcium and vitamin D. Using data from the New England case–control study (1,909 cases and 1,989 controls), we examined dairy foods and nutrients in relation to risk of ovarian cancer overall, histological subtypes and rapidly fatal versus less aggressive disease. We used logistic regression and polytomous logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). In models that were simultaneously adjusted for total (dietary plus supplements) calcium, total vitamin D and lactose, we observed a decreased overall risk of ovarian cancer with high intake of total calcium [Quartile 4 (Q4, >1,319 mg/day) vs. Quartile 1 (Q1, <655 mg/day), OR = 0.62, 95% CI = 0.49–0.79]; the inverse association was strongest for serous borderline and mucinous tumors. High intake of total vitamin D was not associated overall with ovarian cancer risk, but was inversely associated with risk of serous borderline (Q4, >559 IU/day vs. Q1, <164 IU/day, OR = 0.51, 95% CI = 0.34–0.76) and endometrioid tumors (Q4 vs. Q1, OR = 0.55, 95% CI = 0.39–0.80). We found no evidence that lactose intake influenced ovarian cancer risk or that risk varied by tumor aggressiveness in the analyses of intake of dairy foods and nutrients. The overall inverse association with high intake of calcium and the inverse associations of calcium and vitamin D with specific histological subtypes warrant further investigation.     

Polymorphisms in the MTHFR and VDR genes and skin cancer risk

Folate and vitamin D have been shown to be influenced by ultraviolet (UV) radiation. UVA radiation can break down plasma folate, whereas vitamin D can be synthesized in UVB-exposed skin. Folate metabolism is involved in DNA synthesis and repair, and vitamin D processes anti-proliferative effects. The functions of both nutrients are implicated in skin carcinogenesis. We evaluated genetic polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene (C677T and A1298C) and the vitamin D receptor (VDR) gene (Fok1, Bsm1 and Cdx2) with skin cancer risk in a nested case-control study within the Nurses' Health Study [219 melanoma, 286 squamous cell carcinoma (SCC), 300 basal cell carcinoma (BCC) and 873 controls]. No significant associations were observed for the two MTHFR polymorphisms on skin cancer risk. We observed an interaction between the C677T polymorphism and total folate intake on SCC risk (P, interaction=0.04); the highest risk was observed among women with TT genotype and low folate intake (OR=2.14; 95% CI=1.01-4.50). The VDR Bsm1 BB genotype was significantly associated with an increased SCC risk (OR=1.51; 95% CI=1.00-2.28). An interaction between the Bsm1 polymorphism and total vitamin D intake on SCC was observed, with the highest risk seen in women with the BB genotype and high vitamin D intake (OR=2.38; 95% CI=1.22-4.62) (P, interaction=0.08). This study suggests a possible role of the polymorphisms in MTHFR and VDR interacting with dietary intakes of folate and vitamin D in skin cancer development, especially for SCC. Due to a large number of comparisons and tests, the possible associations should be interpreted with caution and confirmed by other studies.     

Prescribing sunshine: a cross-sectional survey of 500 Australian general practitioners' practices and attitudes about vitamin D

This study aimed to assess the attitudes, practices and knowledge of general practitioners (GPs) with regards to vitamin D. A cross-sectional survey of a random sample of GPs stratified by location of practice (rural/remote or metropolitan) and employment status (full-time or part-time) in New South Wales (NSW), Australia was conducted. Of 500 respondents, 58.1% (95% CI 53.8-62.4) reported that up to 39% of their tested patients showed vitamin D deficiency or insufficiency and a further 37.7% (95% CI 33.5-41.9) of respondents said that over 40% of their patients were vitamin D insufficient. Vitamin D supplementation and advice to receive more natural sunlight were the most common ways vitamin D insufficiency was managed (97.1%; 95% CI 95.6-98.6 and 82%, 95% CI 78.6-85.4, respectively). Some gaps in knowledge were identified. Most respondents (64%; 95% CI 59.8-68.2) believed that a person of average sun sensitivity required 10 min of direct sun exposure during summer in peak UV time and a further 21.6% (95% CI 18.0-25.2) believed that people required 30 min of direct sun. A third of respondents (33.1%; 95% CI 29.0-37.2) advised their patients to use sun protection at all times during winter. In general, the attitude items showed that respondents expressed greater concern about vitamin D deficiency than skin cancer. The results reveal some confusion in general practice regarding vitamin D, sun exposure, sun protection and skin cancer risk. Some of the advice that GPs are offering may needlessly increase their patients' risk for vitamin D insufficiency or skin cancer.     

Association between dietary vitamin C intake and risk of esophageal cancer: A dose–response meta‐analysis

While several epidemiological studies have investigated the association between vitamin C and risk of esophageal cancer, the results remain inconsistent. In the present study, a meta‐analysis was conducted to assess the impact of dietary vitamin C intake on esophageal cancer risk. Online databases were searched up to March 29, 2015, for studies on the association between dietary vitamin C intake and esophageal cancer risk. Pooled risk ratios (RRs) or odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random‐effects model. Dose–response analyses were performed using the method of restricted cubic splines with four knots at percentiles of 5, 35, 65 and 95% of the distribution. Publication bias was estimated using Egger's tests and funnel plots. In all, 15 articles were included in this meta‐analysis, including 20 studies, containing 7063 controls and 3955 cases of esophageal cancer. By comparing the highest vs. the lowest categories of vitamin C intake, we found that vitamin C was inversely associated with the risk of esophageal cancer [overall OR = 0.58, 95% CI = 0.49–0.68, I² = 56%]. A linear dose–response relationship was found. With an increase in dietary vitamin C intake of 50 mg/day, the risk of esophageal cancer statistically decreased by 13% (OR = 0.87, 95% CI = 0.80–0.93, p_linearity = 0.0002). In conclusion, our analysis suggested that the higher intake of dietary vitamin C might have a protective effect against esophageal cancer.     

Micronutrients and the risk of renal cell cancer: a case-control study from Italy

The role of various micronutrients on the risk of renal cell cancer (RCC) was examined in a multicentric case-control study from Italy, in which information on dietary habits were collected using a validated food-frequency questionnaire. Cases were 767 patients (494 men and 273 women) with incident, histologically confirmed RCC; controls were 1,534 subjects (988 men and 546 women) admitted to the same hospitals as cases for a wide spectrum of acute, nonneoplastic conditions. After allowing for energy and other major covariates, a significant inverse association was found for vitamin E (odds ratio, OR, for the highest quintile of intake versus the lowest one 0.56, 95% confidence interval, CI 0.41-0.75), and vitamin C (OR = 0.72, 95% CI = 0.54-0.96), although the trend in risk for vitamin C was of borderline significance. No significant trend of decreasing risk was found for other micronutrients analyzed, although for most of them the risk estimates were below unity for intakes above the lowest. The ORs for the upper quintile of intake when compared with the lowest one were 0.80 (95% confidence interval, CI = 0.59-1.08) for retinol, 0.82 (95% CI = 0.61-1.10) for alpha-carotene, 0.90 (95% CI = 0.68-1.20) for beta-carotene, 0.94 (95% CI = 0.73-1.21) for beta-criptoxanthin, 0.85 (95% CI = 0.63-1.14) for lutein/zeaxanthin, 0.76 (95% CI = 0.57-1.01) for vitamin D, 0.75 (95% CI = 0.55-1.01) for thiamine, 0.88 (95% CI = 0.66-1.19) for riboflavin, 0.85 for vitamin B6 (95% CI = 0.64-1.13), 0.85 (95% CI = 0.64-1.12) for folate and 0.80 (95% CI = 0.60-1.07) for niacin. No meaningful associations emerged for lycopene (OR = 1.11). The present findings support a possible beneficial effect of vitamin E and C on RCC.     

Estimated intake of vitamin D and its interaction with vitamin A on lung cancer risk among smokers

Data are very limited on vitamin D and lung cancer prevention in high‐risk populations. The authors investigated whether estimated vitamin D intake was associated with lung cancer risk and whether effect modification by vitamin A existed among current/former heavy smokers and workers with occupational exposure to asbestos. A case–cohort study selected 749 incident lung cancers and 679 noncases from the Carotene and Retinol Efficacy Trial (CARET), 1988–2005. The active intervention was supplementation of 30 mg β‐carotene + 25,000 IU retinyl palmitate/day. Baseline total intake including both diet (from food frequency questionnaire) and personal supplements (from brand names linked to the labeled potencies) was assessed. Hazard ratios (HRs) were estimated by Cox proportional hazard models. No significant association of total vitamin D intake with lung cancer was observed overall. However, total vitamin D intake ≥600 versus <200 IU/day was associated with a lower risk of non‐small cell lung cancer among former smokers [HR = 0.36, 95% confidence interval (CI) = 0.13–0.96]. Total vitamin D intake ≥400 versus <400 IU/day was associated with a lower risk of total lung cancer among participants who received the CARET active intervention (HR = 0.56, 95% CI = 0.32–0.99) and among those who had total vitamin A intake ≥1,500 µg/day retinol activity equivalent (RAE; HR = 0.46, 95% CI = 0.23–0.91). The beneficial associations were attenuated among those who did not receive the CARET active intervention or who had total vitamin A intake <1,500 µg/day RAE (p‐interaction = 0.02 for current smokers). Our observation suggests that vitamin A may assist vitamin D in preventing lung cancer among smokers.     

Personal history of non‐melanoma skin cancer diagnosis and death from melanoma in women

Melanoma incidence is increasing. We evaluated risk of melanoma death after diagnosis of non‐melanoma skin cancer (NMSC). We followed 77,288 female American nurses from the Nurses’ Health Study from 1986 to 2012. We used Cox proportional hazards models to determine the hazard ratio (HR) of lethal and non‐lethal melanoma diagnosis and melanoma death, according to personal NMSC history. Among melanoma cases, we examined the HR of melanoma death and the odds ratio (OR) of melanoma with a Breslow thickness ≥0.8 mm or Clark's levels of IV and V according to history of NMSC. We documented 930 melanoma cases without NMSC history and 615 melanoma cases with NMSC history over 1.8 million person‐years. The multivariate‐adjusted HR (95% confidence interval) of melanoma death associated with personal history of NMSC was 2.89 (1.85–4.50). Women with history of NMSC were more likely to develop non‐lethal melanoma than lethal melanoma (HR (95% CI): 2.31 (2.05–2.60) vs. 1.74 (1.05–2.87)). Among melanoma cases, women with history of NMSC had a non‐significant decreased risk of melanoma deaths (0.87 (0.55–1.37)), Breslow thickness ≥0.8 mm (0.85 (0.59–1.21)) and Clark's levels IV and V (0.81(0.52–1.24)). Women with NMSC history were less likely to be diagnosed with a lethal melanoma than a non‐lethal melanoma, but overall rate of melanoma diagnosis was increased in both subtypes, leading to the increased risk of melanoma death. Our findings suggest the continued need for dermatologic screening for patients after NMSC diagnosis, given increased melanoma risk. Early detection among NMSC patients may decrease deaths from melanoma.