Search

Although smoking and oxidative stress are known contributors to lung carcinogenesis, their mechanisms of action remain poorly understood. To shed light into these mechanisms, we applied a novel approach using Cys34-adductomics in a lung cancer nested case-control study (n = 212). Adductomics profiles were integrated with DNA-methylation data at established smoking-related CpG sites measured in the same individuals. Our analysis identified 42 Cys34-albumin adducts, of which 2 were significantly differentially abundant in cases and controls: adduct of N-acetylcysteine (NAC, p = 4.15 × 10-3 ) and of cysteinyl-glycine (p = 7.89 × 10-3 ). Blood levels of the former were found associated to the methylation levels at 11 smoking-related CpG sites. We detect, for the first time in prospective blood samples, and irrespective of time to diagnosis, decreased levels of NAC adduct in lung cancer cases. Altogether, our results highlight the potential role of these adducts in the oxidative stress response contributing to lung carcinogenesis years before diagnosis.

DNA methylation changes are associated with cigarette smoking. We used the Illumina Infinium HumanMethylation450 array to determine whether methylation in DNA from pre-diagnostic, peripheral blood samples is associated with lung cancer risk. We used a case-control study nested within the EPIC-Italy cohort and a study within the MCCS cohort as discovery sets (a total of 552 case-control pairs). We validated the top signals in 429 case-control pairs from another 3 studies. We identified six CpGs for which hypomethylation was associated with lung cancer risk: cg05575921 in the AHRR gene (p-valuepooled = 4 × 10-17 ), cg03636183 in the F2RL3 gene (p-valuepooled = 2 × 10 - 13 ), cg21566642 and cg05951221 in 2q37.1 (p-valuepooled = 7 × 10-16 and 1 × 10-11 respectively), cg06126421 in 6p21.33 (p-valuepooled = 2 × 10-15 ) and cg23387569 in 12q14.1 (p-valuepooled = 5 × 10-7 ). For cg05951221 and cg23387569 the strength of association was virtually identical in never and current smokers. For all these CpGs except for cg23387569, the methylation levels were different across smoking categories in controls (p-valuesheterogeneity ≤ 1.8 x10 - 7 ), were lowest for current smokers and increased with time since quitting for former smokers. We observed a gain in discrimination between cases and controls measured by the area under the ROC curve of at least 8% (p-values ≥ 0.003) in former smokers by adding methylation at the 6 CpGs into risk prediction models including smoking status and number of pack-years. Our findings provide convincing evidence that smoking and possibly other factors lead to DNA methylation changes measurable in peripheral blood that may improve prediction of lung cancer risk.

Background Few occupational studies have addressed head and neck cancer, and these studies have been predominantly conducted in men. Accordingly, our objective was to investigate the association between head and neck cancer and occupation in women. Methods ICARE, a French population-based case–control study, included 296 squamous cell carcinomas of the head and neck in women and 775 controls. Lifelong occupational history was collected. Odds ratios (ORs) and 95% confidence intervals (CI), adjusted for smoking, alcohol drinking and education level, were estimated for occupations and industries. Results An elevated OR was observed for working proprietors working for 10 years or more (OR = 3.83, 95% CI: 1.12–13.0) with a significant trend with duration of employment (P = 0.047). Elevated but non-significant ORs were observed for street vendors (OR = 3.76, 95% CI: 0.99–14.3, P for trend = 0.13), bakers (OR = 4.19, 95% CI: 0.63–27.9, P for trend = 0.06), and welders and flame cutters (OR = 2.18, 95% CI: 0.33–14.4, P for trend = 0.05). Conclusions This exploratory study suggests a role of occupational exposures in the development of HN cancer in women. Further investigations of exposures to specific agents are needed. Am. J. Ind. Med. 57:1386–1397, 2014. © 2014 Wiley Periodicals, Inc.