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TGFB1 and TGFBR2 functional polymorphisms and risk of esophageal squamous cell carcinoma: a case–control analysis in a Chinese population

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Abstract

Purpose

Transforming growth factor β1 (TGF-β1) and its receptor II (TGF-βRII) are two key components of TGF-β signaling and play an important role in carcinogenesis. Several functional polymorphisms were identified in TGFB1 and TGFBR2 and associated with elevated serum or plasma level of TGF-β1 and enhanced transcription activity of TGFBR2. This population-based case–control study was to evaluate the contribution of functional polymorphisms in TGFB1 C-509T, Leu10Pro and TGFBR2 G-875A to the risk of esophageal squamous cell carcinoma (ESCC).

Methods

Genotyping was performed using the primer-introduced restriction analysis-PCR assay in 255 ESCC cases and 704 cancer-free controls in a Chinese population.

Results

The variant genotypes (-509CT/TT) of TGFB1 C-509T were associated with a 63% significantly decreased risk of ESCC (adjusted OR = 0.37, 95% CI = 0.27–0.50) compared with -509CC wild-type homozygote. In addition, a moderately decreased risk of ESCC was related to -875GA (adjusted OR = 0.70, 95% CI = 0.49–0.99) but not -875AA genotype (adjusted OR = 1.09, 95% CI = 0.51–2.35) in TGFBR2, compared with -875GG common genotype. Furthermore, subjects carrying variant genotypes either or both of TGFB1 C-509T and TGFBR2 G-875A had a significantly reduced risk of ESCC (adjusted OR = 0.37, 95% CI = 0.26–0.53 for either one variant genotype and adjusted OR = 0.30, 95% CI = 0.19–0.48 for both variant genotypes) in a dose-response manner (χ 2trend  = 33.87, P < 0.001) compared with subjects with both wild-type genotypes.

Conclusions

These results are consistent with our previous findings in gastric cancer and support the hypothesis that genetic variants in TGFB1 and TGFBR2 may modulate the risk of ESCC.

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Abbreviations

TGF-β1:

Transforming growth factor β1

TGF-βRI/II:

Transforming growth factor β receptor types I/II

ESCC:

Esophageal squamous cell carcinoma

SNPs:

Single nucleotide polymorphisms

OR:

Odds ratio

CI:

Confidence interval

LD:

Linkage disequilibrium

PIRA:

Primer-introduced restriction analysis

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Acknowledgments

This study was supported in part by the National Natural Science Foundation of China, Grant numbers: 30571605 and 30671814; Jiangsu Natural Science Foundation, Grant number: BK2005143.

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Authors and Affiliations

  1. Department of Epidemiology and Biostatistics, Nanjing Medical University School of Public Health, 140 Hanzhong Road, 210029, Nanjing, China

    Guangfu Jin, Yimei Deng, Ruifen Miao, Zhibin Hu, Lina Wang, Wensen Chen, Jing Shen, Yaochu Xu & Hongbing Shen

  2. Laboratory of Toxicology, Nanjing Medical University School of Public Health, 210029, Nanjing, China

    Guangfu Jin, Xinru Wang & Hongbing Shen

  3. Yixing People’s Hospital, Yixing City, Jiangsu Province, China

    Yan Zhou, Yongfei Tan & Weiliang Ding

  4. Yangzhong Cancer Institute, Yangzhong City, Jiangsu Province, China

    Jianming Wang & Zhaolai Hua

Authors
  1. Guangfu Jin
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  2. Yimei Deng
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  3. Ruifen Miao
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  4. Zhibin Hu
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  5. Yan Zhou
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  13. Xinru Wang
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  15. Hongbing Shen
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Corresponding author

Correspondence to Hongbing Shen.

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Jin, G., Deng, Y., Miao, R. et al. TGFB1 and TGFBR2 functional polymorphisms and risk of esophageal squamous cell carcinoma: a case–control analysis in a Chinese population. J Cancer Res Clin Oncol 134, 345–351 (2008). https://doi.org/10.1007/s00432-007-0290-1

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  • DOI: https://doi.org/10.1007/s00432-007-0290-1

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