Prostate cancer is one of the most prevalent cancers in men. Exposure to heavy metals and their association with prostate cancer risk has been studied extensively, but combined effects remain largely inconclusive. To elucidate the association between serum concentrations of heavy metals and prostate cancer risk. Inductively coupled plasma mass spectrometry (ICP-MS) was used to determine the concentrations of a panel of 10 heavy metals (Mn, Cu, Zn, As, Se, Sb, Co, Cu, Cd and Pb) in serum samples of 141 cases and 114 controls in the Singapore Prostate Cancer Study. Linear probit regression models were used to estimate risk differences (RDs) and 95% confidence intervals (CIs) for the associations between log-centered serum metal concentrations and prostate cancer risk with adjustment for potential confounders. Bayesian kernel machine regression (BKMR) models were used to account for nonlinear, interactive, and joint metal effects. Using probit regression, four heavy metals (As, Zn, Mn, Sb) were significantly and positively associated with prostate cancer risk in the unadjusted models. Using BKMR analysis, both As and Zn had positive risk differences on prostate cancer risk when all other metals were held fixed at the 25th and 50th percentiles (RD, 25th percentile: As: 0.15, Zn: 0.19, RD, 50th percentile: As: 0.45, Zn: 0.37). In addition, the overall mixture risk difference was positive and the 95% credible intervals did not include 0 when all metals in the mixture were jointly above their 55th percentile, as compared to when all metals were below their median values. In summary, we found positive associations between the serum levels of As and Zn and prostate cancer risk on the risk difference scale using BKMR models. The overall mixture effect was also associated with increased prostate cancer risk. Future studies are warranted to validate these findings in prospective studies.

Vitamin E is a group of antioxidative tocopherols and tocotrienols that play a potential role in chemoprevention. Studies investigating the association between vitamin E and prostate cancer risk have been conflicting. We identified observational and interventional studies examining the association between vitamin E intake and prostate cancer risk from PubMed, EMBASE and the Cochrane Library. A random-effects model was used to perform a meta-analysis and estimate relative risks (RRs) and the corresponding 95% confidence intervals (CIs) of prostate cancer risk according to vitamin E intake. Subgroup analyses were conducted by study design, sample size, study population characteristics, geographical region, and dose of vitamin E intake. The association between dietary (RR = 0.97; 95% CI = 0.92–1.02) and supplemental (RR = 0.99; 95% CI = 0.94–1.04) vitamin E intake on prostate cancer risk was non-significant. In subgroup analyses, supplemental vitamin E was significantly associated with reduced prostate cancer risk in studies in Europe (RR = 0.81, 95% CI = 0.69–0.97). Overall, this meta-analysis demonstrates little evidence for a beneficial effect of vitamin E intake on prostate cancer risk but suggests that there may be some conditions in which supplements could confer a protective effect on prostate cancer risk.

To evaluate associations by EGFR mutation status for lung adenocarcinoma risk among never-smoking Asian women, we conducted a meta-analysis of 11 loci previously identified in genome-wide association studies (GWAS). Genotyping in an additional 10,780 never-smoking cases and 10,938 never-smoking controls from Asia confirmed associations with eight known single nucleotide polymorphisms (SNPs). Two new signals were observed at genome-wide significance (P < 5 × 10⁻⁸), namely, rs7216064 (17q24.3, BPTF), for overall lung adenocarcinoma risk, and rs3817963 (6p21.3, BTNL2) which is specific to cases with EGFR mutations. In further sub-analyses by EGFR status, rs9387478 (ROS1/DCBLD1) and rs2179920 (HLA-DPB1) showed stronger estimated associations in EGFR-positive compared to EGFR-negative cases. Comparison of the overall associations with published results in Western populations revealed that the majority of these findings were distinct, underscoring the importance of distinct contributing factors for smoking and non-smoking lung cancer. Our results extend the catalogue of regions associated with lung adenocarcinoma in non-smoking Asian women and highlight the importance of how the germline could inform risk for specific tumour mutation patterns, which could have important translational implications.

Previous lung diseases (PLD) are known risk factors for lung cancer. However, it remains unclear how the association varies by lung cancer subtype and socio-demographic characteristics. We conducted a systematic literature search in three electronic databases from the inception of each database up until 13 January 2021. A total of 73 studies (18 cohort and 55 case–control studies) consisting of 97 322 cases and 7 761 702 controls were included. Heterogeneity was assessed using the I² statistic. Based on the heterogeneity, either the fixed-effects or random-effects model was used to estimate the pooled summary estimate (PSE) and 95% confidence interval (CI) for the association between PLD and lung cancer risk. A history of asthma, chronic bronchitis, emphysema, pneumonia, tuberculosis, and chronic obstructive pulmonary disease (COPD) was associated with higher lung cancer risk, with a history of COPD and emphysema having at least twofold relative risk. A history of hay fever was associated with lower lung cancer risk (PSE= 0.66, 95% CI= 0.54–0.81), particularly among ever-smokers (PSE= 0.55, 95% CI= 0.41–0.73). Individuals with a diagnosis of asthma, emphysema, or pneumonia within 1–10 years prior to lung cancer diagnosis were observed to have a higher lung cancer risk as compared to those who were diagnosed more than 10 years prior to lung cancer diagnosis. Ever-smokers with a history of COPD or emphysema were observed to have at least twofold relative risk of lung cancer compared to those without this history. Due to the observed association between PLD with higher risk of lung cancer, it is advisable that individuals with PLD should be closely monitored and prioritised for lung cancer screening.