9q33.3, a stress-related chromosome region, contributes to reducing lung squamous cell carcinoma risk.

Human chromosome 9q33.3 is one of the most important loci for pathophysiological stresses with complex genetic traits. We hypothesized that the common single-nucleotide polymorphisms on this region may affect non-small-cell lung cancer risk. We genotyped 43 single-nucleotide polymorphisms that span 13 genes on 9q33.3 in two independent cohorts: the discovery study including 485 cases and 532 controls (North China) and the replicative study including 1063 cases and 1247 controls (South China). Both of the discovery cohort and the replicative cohort were included in the combined study. In the discovery study, we identified a potential protective locus rs10118570 in mitogen-activated protein kinase associated protein 1 with a lower population attributable risk under logistical regression adjusted by age, gender, smoking, and drinking status (adjusted odds ratio [OR] 0.26, 95% confidence interval [CI] 0.10-0.71, p = 1.138 × 10 for genotype GG in lung squamous cell carcinoma). This protective quality increased in a dose-dependent manner as genotype GG decreased (ptrend = 9.675 × 10). Replicative and combined studies showed consistent association for this genotype (replicative: adjusted OR 0.36, 95% CI 0.20-0.66, p = 6.109 × 10, ptrend = 7.386 × 10; combined: adjusted OR 0.33, 95% CI 0.18-0.55, p = 1.259 × 10, ptrend = 7.725 × 10). We concluded that mitogen-activated protein kinase associated protein 1 rs10118570 may be an important protective factor for developing better management strategies in lung squamous cell carcinoma.