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Potentially functional variants of PLCE1 identified by GWASs contribute to gastric adenocarcinoma susceptibility in an eastern Chinese population.

Publication ,  Journal Article
Wang, M; Zhang, R; He, J; Qiu, L; Li, J; Wang, Y; Sun, M; Yang, Y; Wang, J; Yang, J; Qian, J; Jin, L; Ma, H; Wei, Q; Zhou, X
Published in: PLoS One
2012

BACKGROUND: Recent genome-wide association studies (GWAS) have found a single nucleotide polymorphism (SNP, rs2274223 A>G) in PLCE1 to be associated with risk of gastric adenocarcinoma. In the present study, we validated this finding and also explored the risk associated with another unreported potentially functional SNP (rs11187870 G>C) of PLCE1 in a hospital-based case-control study of 1059 patients with pathologically confirmed gastric adenocarcinoma and 1240 frequency-matched healthy controls. METHODOLOGY/PRINCIPAL FINDINGS: We determined genotypes of these two SNPs by the Taqman assay and used logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (95% CI). We found that a significant higher gastric adenocarcinoma risk was associated with rs2274223 variant G allele (adjusted OR = 1.35, 95% CI = 1.14-1.60 for AG+GG vs. AA) and rs11187870 variant C allele (adjusted OR = 1.26, 95% CI = 1.05-1.50 for CG+CC vs. GG). We also found that the number of combined risk alleles (i.e., rs2274223G and rs11187870C) was associated with risk of gastric adenocarcinoma in an allele-dose effect manner (P(trend) = 0.0002). Stratification analysis indicated that the combined effect of rs2274223G and rs11187870C variant alleles was more evident in subgroups of males, non-smokers, non-drinkers and patients with gastric cardia adenocarcinoma. Further real-time PCR results showed that expression levels of PLCE1 mRNA were significantly lower in tumors than in adjacent noncancerous tissues (0.019±0.002 vs. 0.008±0.001, P<0.05). CONCLUSIONS/SIGNIFICANCES: Our results further confirmed that genetic variations in PLCE1 may contribute to gastric adenocarcinoma risk in an eastern Chinese population.

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Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2012

Volume

7

Issue

3

Start / End Page

e31932

Location

United States

Related Subject Headings

  • Stomach Neoplasms
  • Polymorphism, Single Nucleotide
  • Phosphoinositide Phospholipase C
  • Middle Aged
  • Male
  • Humans
  • Genotype
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • General Science & Technology
 

Citation

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Wang, M., Zhang, R., He, J., Qiu, L., Li, J., Wang, Y., … Zhou, X. (2012). Potentially functional variants of PLCE1 identified by GWASs contribute to gastric adenocarcinoma susceptibility in an eastern Chinese population. PLoS One, 7(3), e31932. https://doi.org/10.1371/journal.pone.0031932
Wang, Mengyun, Ruoxin Zhang, Jing He, Lixin Qiu, Jin Li, Yanong Wang, Menghong Sun, et al. “Potentially functional variants of PLCE1 identified by GWASs contribute to gastric adenocarcinoma susceptibility in an eastern Chinese population.PLoS One 7, no. 3 (2012): e31932. https://doi.org/10.1371/journal.pone.0031932.
Wang, Mengyun, et al. “Potentially functional variants of PLCE1 identified by GWASs contribute to gastric adenocarcinoma susceptibility in an eastern Chinese population.PLoS One, vol. 7, no. 3, 2012, p. e31932. Pubmed, doi:10.1371/journal.pone.0031932.
Wang M, Zhang R, He J, Qiu L, Li J, Wang Y, Sun M, Yang Y, Wang J, Yang J, Qian J, Jin L, Ma H, Wei Q, Zhou X. Potentially functional variants of PLCE1 identified by GWASs contribute to gastric adenocarcinoma susceptibility in an eastern Chinese population. PLoS One. 2012;7(3):e31932.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2012

Volume

7

Issue

3

Start / End Page

e31932

Location

United States

Related Subject Headings

  • Stomach Neoplasms
  • Polymorphism, Single Nucleotide
  • Phosphoinositide Phospholipase C
  • Middle Aged
  • Male
  • Humans
  • Genotype
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • General Science & Technology