Epigenetic smoking scores predict lung and urothelial cancer risk

Researchers evaluated six blood DNA methylation-based smoking predictors in middle-aged and older Australians from the Melbourne Collaborative Cohort Study. The team tested the tools across 2,875 participants with a median age of 61 years, assessing accuracy against self-reported pack-years and testing reliability in 364 duplicated samples. They also analyzed associations with cancer incidence in two nested case-control studies containing 332 lung cancer cases and 426 urothelial cancer cases. All six predictors showed intraclass correlation coefficients above 0.9 and distinguished current from never smokers with areas under the curve between 0.94 and 0.98. The tools explained 35% to 50% of the variance in smoking pack-years. Epigenetic scores positively associated with cancer risk. The mCigarette score showed the strongest link to lung cancer (rate ratio 2.18 per standard deviation), while PCPACKYEARS showed the strongest link to urothelial cancer (rate ratio 1.62).