Evaluating the Association of Eight Polymorphisms with Cancer Susceptibility in a Han Chinese Population

Abstract

BackgroundThe identification of susceptibility genes for specific types of cancer can provide necessary information for the complete characterization of cancer syndromes. Eight single nucleotide polymorphisms (SNPs), rs465498, rs17728461, rs4488809, rs753955, rs13361707, rs9841504, rs2274223, and rs13042395, were reported by genome wide association studies (GWASs) to be closely related to the susceptibility of lung cancer (LC), gastric cancer (GC) or esophageal cancer (EC) in Han population from northern or southern China. However, Chinese Han people from different geographic areas may have different genetic backgrounds. This study aims to assess the genetic associations of the eight SNPs mentioned above with three cancers risk in a Han population from northwest China.MethodsA total of 186 cancer-free controls and 436 cases with non-small cell lung cancer (NSCLC) (159 cases), non-cardia GC (167 cases) or EC (110 cases) were enrolled in this study. Chi-square test and polytomous logistic regression analyses were used to estimate the association between eight cancer-related SNPs and three cancers in a Han Chinese population from northwest China. The logistic regression results were adjusted for confounding factors and Benjamini and Hochberg False Discovery Rate (FDR) method was used to adjust the multiple hypothesis tests. Association analyses by cigarette smoking or alcohol drinking status were analyzed by crossover analyses.ResultsOne of the eight SNPs, rs17728461 was associated with NSCLC susceptibility (in a heterozygous model, OR = 0.44, 95% CI = 0.27–0.72, p = 0.001). Two SNPs, rs753955 and rs13042395, were associated with the risk of non-cardia GC in different genetic models (p < 0.05). No SNPs were associated with EC. The crossover analyses showed that the rs13042395 CT genotype, combined with cigarette smoking or alcohol drinking, could further increase the risk for non-cardia GC (p < 0.05).ConclusionsThese results indicated that rs17728461 may be specifically associated with the risk of NSCLC. rs753955 and rs13042395 were specifically associated with susceptibility to non-cardia GC in Ningxia Han Chinese. Susceptibility-associated polymorphisms in the northwestern Han Chinese were not very consistent with those in the northern Han Chinese or southern Han Chinese. The validation of these findings with a functional evaluation and a larger population is still required.

Environmental factors, seven GWAS‐identified susceptibility loci, and risk of gastric cancer and its precursors in a Chinese population

“…A previous study conducted by Dong et al . found that subjects carrying SLC52A3 rs13042395 T carriers showed a significantly increased risk of noncardia GC when they were alcohol drinkers, similar to the results of our study. In addition, we identified an additive interaction between SLC52A3 rs13042395 and alcohol drinking status, suggesting that SLC52A3 may interact with certain metabolic changes induced by alcohol drinking and influence the susceptibility to GC.…”

ZBTB20 promotes cell migration and invasion of gastric cancer by inhibiting IκBα to induce NF-κB activation

“…However, Shi et al, found a significant association between the rs9841504 polymorphism in ZBTB20 and decreased gastric cancer susceptibility, suggested that the ZBTB20 rs9841504 polymorphism is a protective factor for gastric cancer [11]. Meanwhile, no statistical difference was found between the rs9841504 polymorphism in ZBTB20 and gastric cancer risk in other previous studies [16][17][18]. It is likely that the contradictory results were due to the relatively small sample sizes and different genetic backgrounds.…”

A shared susceptibility locus in p53 for both gastric cancer and esophageal cancer in a northwestern Chinese population

“…Compared with the rs1042522 Pro allele, the rs1042522 Arg allele increased the GC risk by 1.810 times, and the EC risk by 2.285 times as well. A group of studies supported that rs1042522 Arg was a potential cancer genetic risk factor, such as in breast cancer in Turkish patients and cutaneous melanoma in Caucasians [22]. Cheng et al [25] reported that the rs1042522 Arg allele increased the GC risk by 1.17-fold compared with the rs1042522 Pro allele in a meta-analysis with 7,444 GC cases and 9,984 controls among Eastern Asians.…”

“…Eight SNPs, including rs1042522, rs2395655, rs3176320, rs3829963, rs3829964, rs4135234, rs730506 and rs762624, in p53 or CDKN1A were tested. The polymerase chain reaction (PCR) primer pairs used to amplify the eight SNPs were the same as previously described [22] and were designed by Oligo5.0 software.…”