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Genetic variations of mTORC1 genes and risk of gastric cancer in an Eastern Chinese population.

Publication ,  Journal Article
He, J; Wang, M-Y; Qiu, L-X; Zhu, M-L; Shi, T-Y; Zhou, X-Y; Sun, M-H; Yang, Y-J; Wang, J-C; Jin, L; Wang, Y-N; Li, J; Yu, H-P; Wei, Q-Y
Published in: Mol Carcinog
November 2013

Mammalian target of rapamycin complex 1 (mTORC1) plays an important role in maintaining proper cellular functions, and genetic variations in this complex may affect cancer risk. In this study, we examined the associations between eight potential functional single nucleotide polymorphisms in the mTORC1 genes (rs2536T>C and rs1883965G>A for mTOR, rs3160T>C, and rs26865A>G for mLST8, rs3751934C>A, rs1062935T>C, rs3751932T>C, and rs12602885G>A for Raptor, not included in published gastric cancer genome-wide association studies) and gastric cancer risk in 1125 gastric cancer cases and 1196 cancer-free controls. We performed conditional logistic regression and multifactor dimensionality reduction (MDR) analyses to assess their associations with gastric cancer risk. We also used false-positive report probabilities (FPRP) for assessing significant findings. We found that only the rs1883965A variant genotypes were associated with an increased risk of gastric cancer (AG vs. GG: adjusted odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.00-1.59; AA vs. GG: adjusted OR = 1.85, 95% CI = 0.67-5.16 and dominant model: adjusted OR = 1.28, 95% CI = 1.03-1.61). Patients with ≥1 risk genotypes of mTOR had significant increased risk (adjusted OR = 1.25, 95% CI = 1.04-1.49), compared with those having zero risk genotypes. In the stratified analysis, the risk effect of the rs1883965 AG/AA genotypes was evident in subgroups of ever-smokers, non-gastric cardia adenocarcinoma and clinical stage I + II, which were noteworthy findings as evaluated by FPRP. The MDR analysis identified smoking status and rs1883965 as the strongest two-factors for gastric cancer risk. These data support the hypothesis that functional polymorphisms of mTOR may contribute to gastric cancer risk. Clearly, our results require validation in larger studies with different ethnic populations.

Duke Scholars

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Published In

Mol Carcinog

DOI

EISSN

1098-2744

Publication Date

November 2013

Volume

52 Suppl 1

Start / End Page

E70 / E79

Location

United States

Related Subject Headings

  • mTOR Associated Protein, LST8 Homolog
  • TOR Serine-Threonine Kinases
  • Stomach Neoplasms
  • Risk Factors
  • Regulatory-Associated Protein of mTOR
  • Prognosis
  • Polymorphism, Single Nucleotide
  • Polymerase Chain Reaction
  • Oncology & Carcinogenesis
  • Neoplasm Staging
 

Citation

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He, J., Wang, M.-Y., Qiu, L.-X., Zhu, M.-L., Shi, T.-Y., Zhou, X.-Y., … Wei, Q.-Y. (2013). Genetic variations of mTORC1 genes and risk of gastric cancer in an Eastern Chinese population. Mol Carcinog, 52 Suppl 1, E70–E79. https://doi.org/10.1002/mc.22013
He, Jing, Meng-Yun Wang, Li-Xin Qiu, Mei-Ling Zhu, Ting-Yan Shi, Xiao-Yan Zhou, Meng-Hong Sun, et al. “Genetic variations of mTORC1 genes and risk of gastric cancer in an Eastern Chinese population.Mol Carcinog 52 Suppl 1 (November 2013): E70–79. https://doi.org/10.1002/mc.22013.
He J, Wang M-Y, Qiu L-X, Zhu M-L, Shi T-Y, Zhou X-Y, et al. Genetic variations of mTORC1 genes and risk of gastric cancer in an Eastern Chinese population. Mol Carcinog. 2013 Nov;52 Suppl 1:E70–9.
He, Jing, et al. “Genetic variations of mTORC1 genes and risk of gastric cancer in an Eastern Chinese population.Mol Carcinog, vol. 52 Suppl 1, Nov. 2013, pp. E70–79. Pubmed, doi:10.1002/mc.22013.
He J, Wang M-Y, Qiu L-X, Zhu M-L, Shi T-Y, Zhou X-Y, Sun M-H, Yang Y-J, Wang J-C, Jin L, Wang Y-N, Li J, Yu H-P, Wei Q-Y. Genetic variations of mTORC1 genes and risk of gastric cancer in an Eastern Chinese population. Mol Carcinog. 2013 Nov;52 Suppl 1:E70–E79.
Journal cover image

Published In

Mol Carcinog

DOI

EISSN

1098-2744

Publication Date

November 2013

Volume

52 Suppl 1

Start / End Page

E70 / E79

Location

United States

Related Subject Headings

  • mTOR Associated Protein, LST8 Homolog
  • TOR Serine-Threonine Kinases
  • Stomach Neoplasms
  • Risk Factors
  • Regulatory-Associated Protein of mTOR
  • Prognosis
  • Polymorphism, Single Nucleotide
  • Polymerase Chain Reaction
  • Oncology & Carcinogenesis
  • Neoplasm Staging