Associations of genetic variants in the PSCA, MUC1 and PLCE1 genes with stomach cancer susceptibility in a Chinese population

PLoS One. 2015 Feb 6;10(2):e0117576. doi: 10.1371/journal.pone.0117576. eCollection 2015.

Abstract

Background: Several genetic variants including PSCA rs2294008 C>T and rs2976392 G>A, MUC1 rs4072037 T>C, and PLCE1 rs2274223 A>G have shown significant association with stomach cancer risk in the previous genome-wide association studies (GWASs).

Methods: To evaluate associations of these SNPs in the Han Chinese, an independent hospital based case-control study was performed by genotyping these four polymorphisms in a total of 692 stomach cancer cases and 774 healthy controls acquired by using frequency matching for age and gender. False-positive report probability (FPRP) analysis was also performed to validate all statistically significant findings.

Results: In the current study, significant association with stomach cancer susceptibility was observed for all the four polymorphisms of interest. Specifically, a significant increased stomach cancer risk was associated with PSCA rs2294008 (CT vs. CC: adjusted OR = 1.37, 95% CI = 1.07-1.74, and CT/TT vs.CC: adjusted OR = 1.30, 95% CI = 1.03-1.63), PSCA rs2976392 (AG vs. GG: adjusted OR = 1.30, 95% CI = 1.02-1.65, and AG/AA vs. GG: adjusted OR = 1.26, 95% CI = 1.00-1.59), or PLCE1 rs2274223 (AG vs. AA: adjusted OR = 1.48, 95% CI = 1.15-1.90, and AG/GG vs. AA: adjusted OR = 1.45, 95% CI = 1.14-1.84), respectively. In contrast, MUC1 rs4072037 was shown to decrease the cancer risk (CT vs. TT: adjusted OR = 0.77, 95% CI = 0.60-0.98). Patients with more than one risk genotypes had significant increased risk to develop stomach cancer (adjusted OR = 1.30, 95% CI = 1.03-1.64), when compared with those having 0-1 risk genotypes. Stratified analysis indicated that the increased risk was more pronounced in younger subjects, men, ever smokers, smokers with pack years ≤ 27, patients with high BMI, or non-cardia stomach cancer.

Conclusions: This study substantiated the associations between four previous reported genetic variants and stomach cancer susceptibility in an independent Han Chinese population. Further studies with larger sample size and different ethnicities are warranted to validate our findings.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / genetics*
  • Asian People / genetics
  • Case-Control Studies
  • Female
  • GPI-Linked Proteins / genetics
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Mucin-1 / genetics*
  • Neoplasm Proteins / genetics*
  • Phosphoinositide Phospholipase C / genetics*
  • Polymorphism, Single Nucleotide
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology
  • Young Adult

Substances

  • Antigens, Neoplasm
  • GPI-Linked Proteins
  • MUC1 protein, human
  • Mucin-1
  • Neoplasm Proteins
  • PSCA protein, human
  • Phosphoinositide Phospholipase C
  • phospholipase C epsilon

Grants and funding

The study was supported by China National Natural Science Foundation (No. 81370563) grant and Zhejiang Provincial Program for the Cultivation of High-level Innovative Health talents and a Provincial Administration of Traditional Chinese Medicine of Zhejiang Province, China (No.2011ZA072) and Project supported by ministry of health of China-the major medicine science and technology project in Zhejiang province (No. WKJ2012-2-033) and Public welfare technology application research project supported by science technology department of Zhejiang province (No.2012C23108) and Excellent Youth Foundation of Zhejiang Provincial Natural Science (No.LR14H030001) and project of science and technology of Wencheng county. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.