Genetic variants of JNK and p38α pathways and risk of non‐small cell lung cancer in an Eastern Chinese population

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.

Potentially functional genetic variants in the complement‐related immunity gene‐set are associated with non‐small cell lung cancer survival

“…2 The leftmost was used as the reference. 3 14 missing date were excluded. 4 rs73049469 and rs3788142 in an additive genetic model.…”

“…2 14 missing date were excluded. 3 10 missing date were excluded. 4 Risk genotypes were VWF rs73049469 CA + AA and ITGB2 rs3788142 GA + AA.…”

“…2 Obtained from an additive genetic model with adjustment for age, sex, stage, histology, smoking status, chemotherapy, radiotherapy, surgery, PC1, PC2, PC3 and PC4. 3 FDR and FPRP were available in the PLCO dataset because the HLCS study provided only the summary data. 4 Obtained from an additive genetic model with adjustment for age, sex, stage, histology, smoking status, chemotherapy, radiotherapy, surgery, PC1, PC2 and PC3.…”

“…Clinically, the known clinicopathological variables, such as age, sex, performance status and most importantly tumor stage, are commonly used for predicting prognosis; however, the response of individuals is heterogeneous, suggesting that genetic factors also account for the variability in treatment response, likely due to genetic variation in drug disposition, pharmacokinetic effects and host immunity. Some studies found that single‐nucleotide polymorphisms (SNPs) could influence short‐term response and long‐term prognosis of cancer patients . Therefore, identifying the role of these genetic factors in the prognosis may lead to a better understanding of lung cancer prognosis.…”

“…Some studies found that single-nucleotide polymorphisms (SNPs) could influence short-term response and long-term prognosis of cancer patients. [3][4][5] Therefore, identifying the role of these genetic factors in the prognosis may lead to a better understanding of lung cancer prognosis.…”