Previous meta-analyses of randomized controlled trials (RCTs) of vitamin D supplementation and total cancer incidence and mortality found inconsistent results, and most included trials administered generally low doses of vitamin D (≤ 1100 IU/day). We updated the meta-analysis by incorporating recent RCTs that have tested higher doses of vitamin D supplements. PubMed and Embase were searched from the inception to November, 2018. Summary relative risks (RRs) and 95% confidence intervals (CIs) were estimated using a random-effects model. For total cancer incidence, 10 trials were included (6,547 cases; 3-10 years of follow-up; 54-135 nmol/L of attained levels of circulating 25(OH)vitamin D [25(OH)D] in the intervention group). The summary RR was 0.98 (95% CI, 0.93 to 1.03; P=.42; I²=0%). The results remained null across subgroups tested, including even when attained 25(OH)D levels exceeded 100 nmol/L (RR, 0.95; 95% CI, 0.83 to 1.09; P=.48; I²=26%). For total cancer mortality, 5 trials were included (1,591 deaths; 3-10 years of follow-up; 54-135 nmol/L of attained levels of circulating 25(OH)D in the intervention group). The summary RR was 0.87 (95% CI, 0.79 to 0.96; P=.005; I²=0%), which was largely attributable to interventions with daily dosing (as opposed to infrequent bolus dosing). No statistically significant heterogeneity was observed by attained levels of circulating 25(OH)D (P_{heterogeneity}=.83), with RR being 0.88 (95% CI, 0.78 to 0.98; P=.02; I²=0%) for ≤ 100 nmol/L and 0.85 (95% CI, 0.70-1.03; P=.11; I²=0%) for > 100 nmol/L. In an updated meta-analysis of RCTs, vitamin D supplementation significantly reduced total cancer mortality but did not reduce total cancer incidence.

Adiposity, measured by body mass index, is implicated in carcinogenesis. While adult weight gain has diverse advantages over body mass index in measuring adiposity, systematic reviews on adult weight gain in relation to adiposity-related cancers are lacking. PubMed and Embase were searched through September 2014 for prospective observational studies investigating the relationship between adult weight gain and the risk of 10 adiposity-related cancers. Dose-response meta-analyses were performed using a random-effects model to estimate summary relative risk (RR) and 95% confidence interval (CI) for each cancer type. All statistical tests were two-sided. A total of 50 studies were included. For each 5kg increase in adult weight gain, the summary relative risk was 1.11 (95% CI = 1.08 to 1.13) for postmenopausal breast cancer among no- or low-hormone replacement therapy (HRT) users, 1.39 (95% CI = 1.29 to 1.49) and 1.09 (95% CI = 1.02 to 1.16) for postmenopausal endometrial cancer among HRT nonusers and users, respectively, 1.13 (95% CI = 1.03 to 1.23) for postmenopausal ovarian cancer among no or low HRT users, 1.09 (95% CI = 1.04 to 1.13) for colon cancer in men. The relative risk of kidney cancer comparing highest and lowest level of adult weight gain was 1.42 (95% CI = 1.11 to 1.81). Adult weight gain was unrelated to cancers of the breast (premenopausal women, postmenopausal HRT users), prostate, colon (women), pancreas, and thyroid. An increase in risk associated with adult weight gain for breast cancer was statistically significantly greater among postmenopausal women (P_{heterogeneity} = .001) and HRT nonusers (P_{heterogeneity} = .001); that for endometrial cancer was alike among HRT nonusers (P_{heterogeneity} = .04). Avoiding adult weight gain itself may confer protection against certain types of cancers, particularly among HRT nonusers.

Whether the risk of gastric cancer varies by the types of meat consumption still remains disputable. The purpose of this meta-analysis was to identify the exact associations that red, processed, and white meat have with gastric cancer. We searched relevant studies in Medline, EMBASE, and the Cochrane Library before November 2018, including cohort and case-control studies. We used random-effect models to estimate the adjusted relative risk (RR), and Egger’s tests to evaluate publication bias. Through stepwise screening, 43 studies were included in this analysis (11 cohort studies and 32 case-control studies with 16,572 cases). In a meta-analysis for the highest versus lowest categories of meat consumption, both red (RR: 1.41, 95% confidence interval (CI): 1.21–1.66) and processed (RR: 1.57, 95% CI: 1.37–1.81) meat consumption were positively associated with gastric cancer risk, while white meat consumption was negatively associated with gastric cancer risk (RR: 0.80, 95% CI: 0.69–0.92). In a dose–response meta-analysis, the RRs of gastric cancer were 1.26 (95% CI: 1.11–1.42) for every 100 g/day increment in red meat consumption, 1.72 (95% CI: 1.36–2.18) for every 50 g/day increment in processed meat consumption, and 0.86 (95% CI: 0.64–1.15) for every 100 g/day increment in white meat consumption. The increase of white meat consumption may reduce the risk of gastric cancer, while red or processed meat may increase the risk of gastric cancer. Further studies are required to identify these associations, especially between white meat and gastric cancer.

Observational studies suggest that effects of vitamin D may be stronger for cancer mortality than for incidence. Yet, existing randomised controlled trials (RCTs) of vitamin D supplementation have limited power to examine the relationships as their primary end points are not cancer incidence or mortality. Meta-analyses of RCTs of vitamin D supplementation and total cancer incidence and mortality were conducted. Over 2-7 years of duration, vitamin D supplementations had little effect on total cancer incidence (400-1100 IU per day, summary relative risk (RR)=1.00, 95% confidence interval (CI)=0.94-1.06, I(2)=0%; four RCTs with combined 4333 cases), but significantly reduced total cancer mortality (400-833 IU per day, summary RR=0.88, 95% CI=0.78-0.98, I(2)=0%, three RCTs with combined 1190 deaths). Over 2-7 years of duration, the benefit of vitamin D supplementation may be limited to cancer mortality.

Digestive system cancers (DSCs) include cancers of the digestive tract (mouth, throat, esophagus, stomach, small intestine, colorectum) and cancers of digestive accessory organs (pancreas, gallbladder, liver). While individual DSCs are etiologically heterogeneous, accumulating evidence suggests the potential presence of common carcinogenic pathways underlying DSCs. The most substantiated is the proinflammatory pathway mediated by cyclooxygenase (COX)-2 enzyme. For instance, a functional polymorphism in the COX-2 gene was associated with an increased risk of DSCs, in particular.¹ Furthermore, observational studies and randomized clinical trials consistently observed that aspirin, which inhibits COX-2, was notably protective against DSCs.^2,3 Thus, factors that affect the COX-2 pathway may modify the risk of overall DSC. One potential candidate is physical activity (PA), which is shown to reduce the COX-2 proinflammatory pathway.⁴ In addition, the benefit of PA on colorectal cancer survival was confined to COX-2–positive cancers.⁵