Ecological studies in North America have suggested that mortality from several potentially life-threatening chronic health conditions such as cancer, cardiovascular diseases, and diabetes mellitus would increase with increasing latitude, that is, with residence increasingly distant from the equator.^1,2 Other studies have shown that the survival of patients with cardiovascular disease or with some cancer (eg, lung, colorectal, and breast cancer) was greater if the diagnosis was made during summer as compared with the winter.^3,4 Increasing distance from the equator and winter period were equated to decreasing exposure to sunlight, especially to UV-B radiation (280-315 nm) because with increasing latitude, amounts of UV-B radiation reaching the earth surface decrease faster than amounts of UV-A radiation (315-400 nm).⁵ Also, seasonal variations are more pronounced for UV-B radiation than for the UV-A radiation.⁵ Because UV-B radiation is necessary for the synthesis of vitamin D in the skin, it has been hypothesized that associations found between latitude or seasonality and mortality from several chronic conditions could be owing to variations in vitamin D status.^6-10Some food products may also represent a source of vitamin D, although of highly variable content (eg, fortified foods, oily fish, eggs, and butter). Hence, low vitamin D status could proceed from the conjunction of insufficient intakes (exogenous source) and of insufficient skin synthesis (endogenous source) of vitamin D. Biological findings have reinforced the likelihood of the vitamin D hypothesis. First, vitamin D receptors have been found in various organs, and activation of these receptors by 1α,25 dihydroxyvitamin D₃ (calcitriol), the physiologically active form of vitamin D, induces cell differentiation and inhibits proliferation, invasiveness, angiogenesis, and metastatic potential.^11,12 These biological phenomena are typical of cancer genesis and some of them (eg, differentiation and proliferation) are also involved in cardiovascular ischemic diseases. Second, many tissues express the 1α-hydroxylase enzyme.¹¹ So, after 25-hydroxylation of vitamin D in the liver, many cell types are able to convert the circulating 25-hydroxyvitamin D into 1α,25-dihydroxyvitamin D, and autocrine or paracrine production of 1α,25-dihydroxyvitamin D would depend on serum concentration of 25-hydroxyvitamin D.

We conducted a systematic meta‐analysis of observational studies on cigarette smoking and cancer from 1961 to 2003. The aim was to quantify the risk for 13 cancer sites, recognized to be related to tobacco smoking by the International Agency for Research on Cancer (IARC), and to analyze the risk variation for each site in a systematic manner. We extracted data from 254 reports published between 1961 and 2003 (177 case‐control studies, 75 cohorts and 2 nested case‐control studies) included in the 2004 IARC Monograph on Tobacco Smoke and Involuntary Smoking. The analyses were carried out on 216 studies with reported estimates for ‘current’ and/or ‘former’ smokers. We performed sensitivity analysis, and looked for publication and other types of bias. Lung (RR = 8.96; 95% CI: 6.73–12.11), laryngeal (RR = 6.98; 95% CI: 3.14–15.52) and pharyngeal (RR = 6.76; 95% CI: 2.86–15.98) cancers presented the highest relative risks (RRs) for current smokers, followed by upper digestive tract (RR = 3.57; 95% CI: 2.63–4.84) and oral (RR = 3.43; 95% CI: 2.37–4.94) cancers. As expected, pooled RRs for respiratory cancers were greater than the pooled estimates for other sites. The analysis of heterogeneity showed that study type, gender and adjustment for confounding factors significantly influence the RRs estimates and the reliability of the studies.

Metformin, an insulin-lowering agent, has been associated with decreased cancer risk in epidemiologic studies in diabetic patients. We performed a comprehensive literature search and meta-analysis of epidemiologic studies to assess the effect of metformin on cancer incidence and mortality in diabetic patients, using Pubmed, ISI Web of Science, Embase, and the Cochrane library until May 2009, with no language or time restrictions. Independent reports with sufficient information to allow risk estimation of cancer risk/mortality and a measure of uncertainty were reviewed and cross-checked independently by three investigators. Eleven studies were selected for relevance in terms of intervention, population studied, independence, and reporting of cancer incidence or mortality data, reporting 4,042 cancer events and 529 cancer deaths. A 31% reduction in overall summary relative risk (0.69; 95% confidence interval, 0.61-0.79) was found in subjects taking metformin compared with other antidiabetic drugs. The inverse association was significant for pancreatic and hepatocellular cancer, and nonsignificant for colon, breast, and prostate cancer. A trend to a dose-response relationship was noted. Metformin is associated with a decreased risk of cancer incidence compared with other treatments among diabetic patients. Given the retrospective nature of most studies and the possibility that the control treatments increase risk, phase II trials are needed before large cancer prevention trials are launched. Cancer Prev Res; 3(11); 1451–61. ©2010 AACR.