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Polymorphisms in mTORC1 genes modulate risk of esophageal squamous cell carcinoma in eastern Chinese populations.

Publication ,  Journal Article
Zhu, M-L; Yu, H; Shi, T-Y; He, J; Wang, M-Y; Li, Q-X; Sun, M-H; Jin, L; Yang, Y-J; Wang, J-C; Xiang, J-Q; Wei, Q-Y
Published in: J Thorac Oncol
June 2013

INTRODUCTION: Mammalian target of rapamycin complex 1 (mTORC1) is an evolutionary conserved multiprotein complex that functions as a key regulator of gene transcription, protein translation, and autophagy. No studies have assessed associations between functional single nucleotide polymorphisms (SNPs) in mTORC1 genes and risk of esophageal squamous cell carcinoma (ESCC). METHODS: : In a case-control study of 1126 ESCC patients and 1131 cancer-free controls, we genotyped eight SNPs in mTORC1 (mTOR rs1883965 G>A and rs2536 T>C, mLST8 rs3160 C>T and rs26865 G>A, RPTOR rs3751934 C>A, rs1062935 T>C, rs3751932 T>C and rs12602885 G>A) and assessed their associations with risk of ESCC. RESULTS: In the single-locus analyses, we found a significantly altered risk of ESCC associated with mTOR rs1883965 A variant genotypes (adjusted OR = 1.27 and 1.26; 95% confidence interval = 1.01-1.60 and 1.01-1.58 for GA and GA/AA, respectively, compared with GG) but not with other SNPs. In the combined analysis of the eight SNPs, we found individuals with two or more unfavorable genotypes exhibited an increased risk for ESCC (adjusted OR = 1.35; 95% confidence interval = 1.20-1.62), compared with those with less than two unfavorable genotypes. Such a cumulative effect was dose-dependent (ptrend = 0.004). In the multiple dimension reduction analysis, mTOR rs1883965 was consistently suggested as the strongest individual factor for ESCC risk, and the model including all SNPs yielded the lowest prediction error of 17.66% for model validation. CONCLUSIONS: These findings suggest that functional SNPs of mTORC1 genes may individually or collectively contribute to ESCC risk. Further validation of these findings is warranted.

Duke Scholars

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Published In

J Thorac Oncol

DOI

EISSN

1556-1380

Publication Date

June 2013

Volume

8

Issue

6

Start / End Page

788 / 795

Location

United States

Related Subject Headings

  • TOR Serine-Threonine Kinases
  • Risk Factors
  • Prognosis
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Multiprotein Complexes
  • Middle Aged
  • Mechanistic Target of Rapamycin Complex 1
  • Male
  • Humans
 

Citation

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Zhu, M.-L., Yu, H., Shi, T.-Y., He, J., Wang, M.-Y., Li, Q.-X., … Wei, Q.-Y. (2013). Polymorphisms in mTORC1 genes modulate risk of esophageal squamous cell carcinoma in eastern Chinese populations. J Thorac Oncol, 8(6), 788–795. https://doi.org/10.1097/JTO.0b013e31828916c6
Zhu, Mei-Ling, Hongping Yu, Ting-Yan Shi, Jing He, Meng-Yun Wang, Qiao-Xin Li, Meng-Hong Sun, et al. “Polymorphisms in mTORC1 genes modulate risk of esophageal squamous cell carcinoma in eastern Chinese populations.J Thorac Oncol 8, no. 6 (June 2013): 788–95. https://doi.org/10.1097/JTO.0b013e31828916c6.
Zhu M-L, Yu H, Shi T-Y, He J, Wang M-Y, Li Q-X, et al. Polymorphisms in mTORC1 genes modulate risk of esophageal squamous cell carcinoma in eastern Chinese populations. J Thorac Oncol. 2013 Jun;8(6):788–95.
Zhu, Mei-Ling, et al. “Polymorphisms in mTORC1 genes modulate risk of esophageal squamous cell carcinoma in eastern Chinese populations.J Thorac Oncol, vol. 8, no. 6, June 2013, pp. 788–95. Pubmed, doi:10.1097/JTO.0b013e31828916c6.
Zhu M-L, Yu H, Shi T-Y, He J, Wang M-Y, Li Q-X, Sun M-H, Jin L, Yang Y-J, Wang J-C, Xiang J-Q, Wei Q-Y. Polymorphisms in mTORC1 genes modulate risk of esophageal squamous cell carcinoma in eastern Chinese populations. J Thorac Oncol. 2013 Jun;8(6):788–795.
Journal cover image

Published In

J Thorac Oncol

DOI

EISSN

1556-1380

Publication Date

June 2013

Volume

8

Issue

6

Start / End Page

788 / 795

Location

United States

Related Subject Headings

  • TOR Serine-Threonine Kinases
  • Risk Factors
  • Prognosis
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Multiprotein Complexes
  • Middle Aged
  • Mechanistic Target of Rapamycin Complex 1
  • Male
  • Humans