Cancer
A prospective investigation on DNA methylation-based inflammation risk scores and lung cancer among never smokers Mohammad Rahman* Mohammad Rahman Rahman Rahman Rahman Rahman Rahman Rahman Rahman Rahman Rahman Rahman Rahman Rahman National Cancer Institute, Division of Cancer Epidemiology and Genetics
Introduction: Inflammation plays a key role in carcinogenesis. We previously observed an inverse association between plasma C-reactive protein (CRP) and lung cancer risk among never-smokers. CRP fluctuates with acute inflammation, and a single measurement may not capture inflammation relevant for carcinogenesis. DNA methylation–based inflammation risk scores (DNAm-IRS) may better reflect longer-term inflammatory biology. Here, we evaluate DNAm-IRS with lung cancer among never-smokers.
Methods: This nested case-control study included 683 never-smoking women with incident lung cancer and 683 matched controls from the Shanghai Women’s Health Study. Four DNAm-IRS were calculated as weighted sums of CRP-related CpG sites using established algorithms: IRSLigthart (52 CpGs), IRSElnet (1,334 CpGs), IRSWielscher (1,333 CpGs), and IRSHillary (32,196 CpGs). Conditional logistic regression, adjusting for age and body mass index, was used to evaluate associations with overall lung cancer and lung adenocarcinoma, the most common histologic subtype among never smokers.
Results: Among controls with plasma CRP data (n = 214), Spearman correlations between biochemical CRP and DNAm-IRS were 0.20 (p= 3.4×10⁻³) for IRSLigthart, 0.31 (p= 4.6×10⁻⁶) for IRSElnet, 0.13 (p= 6.7×10⁻²) for IRSWielscher, and −0.02 (p= 7.4×10⁻¹) for IRSHillary. Higher DNAm-IRS was associated with lower lung cancer risk among never-smoking women. Per SD increase, IRSWielscher was associated with reduced risk of overall lung cancer (OR=0.87; 95% CI: 0.77–0.97; p=0.017) and lung adenocarcinoma (OR=0.83; 95% CI: 0.71–0.97; p=0.018). IRSLigthart was also inversely associated with overall lung cancer risk (OR=0.85; 95% CI: 0.78–0.97; p=0.003).
Conclusion: Our results suggest that, in the absence of a prevailing inflammatory trigger such as smoking, select CRP-related DNAm signatures are associated with lower lung cancer risk. Replication and mechanistic studies are needed.