Genetic variants of JNK and p38α pathways and risk of non‐small cell lung cancer in an Eastern Chinese population. Issue 4 (16th November 2016)

• Record Type: Journal Article
• Authors: Jia, Ming; Zhu, Meiling; Zhou, Fei; Wang, Mengyun; Sun, Menghong; Yang, Yajun; Wang, Xiaofeng; Wang, Jiucun; Jin, Li; Xiang, Jiaqing; Zhang, Yawei; Chang, Jianhua; Wei, Qingyi
• Is Part Of: International journal of cancer. Volume 140:Issue 4(2017:Feb. 15)
• Page Start: 807
• Page End: 817
• Publication Date: 2016-11-16
• Subjects: single nucleotide polymorphisms -- non‐small cell lung cancer -- case‐control study -- p38a pathway -- JNK pathway; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.30508
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract : The JNK and p38α pathways play an important role in carcinogenesis. Therefore, we hypothesize that single nucleotide polymorphisms (SNPs) of genes involved in these pathways are associated with risk of lung cancer. We first selected and genotyped 11 independent SNPs of the JNK and p38α pathway‐related genes in a discovery set of 1, 002 non‐small cell lung cancer (NSCLC) cases and 1, 025 cancer‐free controls of Eastern Chinese. Then, we validated those significant SNPs in a replication set of 1, 333 NSCLC cases and 1, 339 cancer‐free controls of Eastern Chinese. Multifactor dimensionality reduction (MDR) and classification and regression tree (CART) analyses were used to identify interactions between significant SNPs and other covariates. In both discovery and replication as well as their pooled analysis, carriers of GADD45G rs8252T variant genotypes had a significantly lower risk of NSCLC (adjusted OR = 0.81 and 0.79, 95% CI = 0.72–0.92 and 0.64–0.99 and p = 0.001 and 0.040 for dominant and recessive genetic models, respectively) and carriers of MAP2K7 rs3679T variant genotypes had an increased risk of NSCLC (adjusted OR = 1.19 and 1.29, 95% CI = 1.05–1.34 and 1.09–1.54 and p = 0.005 and 0.004 for dominant and recessive genetic models, respectively). Furthermore, rs8252 variant CT/TT carriers showed significantly higher levels of GADD45G mRNA expression than CC carriers in the target tissues. We observed some evidence of interactions between rs8252 genotypes and sex in NSCLC risk. These results indicate that GADD45G rs8252 and MAP2K7 rs3679 SNPs may be susceptibility biomarkers for NSCLC in Eastern Chinese populations. Abstract : What's new? Interactions of genetic factors with physiological and environmental factors may play an important role in lung carcinogenesis. This large hospital‐based case‐control study investigated whether genetic variants in the JNK and p38α pathways are associated with non‐small cell lung cancer (NSCLC) susceptibility in an Eastern Chinese population. Using 11 independent and potentially functional SNPs, the authors observed positive associations of MAP2K7 rs3679 and GADD45G rs8252 with NSCLC risk. The results, which support prior evidence from two Asian lung cancer studies, suggest that genetic variation in the JNK and p38α pathways may help explain the association between environmental stresses and lung carcinogenesis.