In contrast, a previous report suggests that individuals with the I157T missense variant of the CHEK2 gene might be at decreased risk of lung cancer and upper aero-digestive cancers.
For instance, a greater absolute risk reduction of lung and upper aerodigestive cancers in smokers than in non-smokers carrying the I157T CHEK2 variant has been observed, as has an interaction between TP53 intron 3 16-bp repeats and multiple X-ray exposures on lung cancer risk.
These results support our hypothesis that the CHEK2 rs2236141 variant modifies lung cancer susceptibility in the Chinese population by affecting CHEK2 expression.
We identified large-effect genome-wide associations for squamous lung cancer with the rare variants BRCA2 p.Lys3326X (rs11571833, odds ratio (OR) = 2.47, P = 4.74 × 10(-20)) and CHEK2 p.Ile157Thr (rs17879961, OR = 0.38, P = 1.27 × 10(-13)).