Abstract
Gastric cancer is a multifactorial disease with the involvement of both genetic and environmental risk factors. Genetic variation in genes encoding cytokines and their receptors determine the intensity of the inflammatory response, which may contribute to individual differences in the outcome and severity of the disease. Transforming growth factor (TGF-β) signaling pathway plays an important role in the genesis and progression of tumors through regulating cell proliferation and differentiation. A hospital-based case–control study was conducted to investigate whether TGF-β1 −509 C/T polymorphism can modify the risk of gastric cancer. Seventy endoscopically and histopathologically confirmed gastric cancer patients and 100 age and sex-matched healthy controls were enrolled in the case–control study. TGF-β1 −509 C/T gene polymorphism was carried out by amplification refractory mutation system polymerase chain reaction (ARMS-PCR) method followed by agarose gel electrophoresis. Statistical analysis was applied to test for the significance of the results. The distribution of TGF-β1 genotypes at −509 C/T were CC 37.14%, CT 50%, and TT 12.86% in gastric cancer patients and CC 52%, CT 42%, and TT 6% in control subjects. The allelic frequencies of C and T were 0.621 and 0.379 in gastric cancer patients and 0.73 and 0.27 in control subjects, respectively. Our study imply that T allele of TGF-β1 −509 C/T genotypes may be a risk factor of genetic susceptibility to gastric cancer in south Indian population.
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References
Cancer (Fact sheet N297). World Health Organization. February 2009 http://www.who.int/mediacentre/factsheets/fs297/en/. Accessed on 24March 2011.
Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55(2):74–108.
Singh K, Ghoshal UC. Causal role of Helicobacter pylori infection in gastric cancer: an Asian enigma. World J Gastroenterol. 2006;12(9):1346–51.
Gao L, Nieters A, Brenner H. Meta-analysis: tumour invasion related genetic polymorphisms and gastric cancer susceptibility. Aliment Pharmacol Therapeut. 2008;28(5):565–73.
Gonzalez CA, Sala N, Capella G. Genetic susceptibility and gastric cancer risk. Int J Canc. 2002;100(3):249–60.
Massague J. TGF beta in cancer. Cell. 2008;134:215–30.
Blobe GC, Schiemann WP, Lodish HF. Role of transforming growth factor beta in human disease. N Engl J Med. 2000;342:1350–8.
Saito H, Tsujitani S, Oka S, Kondo A, Ikeguchi M, Maeta M, et al. An elevated serum level of transforming growth factor-beta 1 (TGF-beta 1) significantly correlated with lymph node metastasis and poor prognosis in patients with gastric carcinoma. Anticancer Res. 2000;20(6B):4489–93.
Siegel PM, Massague J. Cytostatic and apoptotic actions of TGF-beta in homeostasis and cancer. Nat Rev Cancer. 2003;3:807–21.
Cui W, Fowlis DJ, Bryson S, Duffie E, Ireland H, Balmain A, et al. TGFbeta1 inhibits the formation of benign skin tumors, but enhances progression to invasive spindle carcinomas in transgenic mice. Cell. 1996;86(4):531–42.
Wakefield LM, Yang YA, Dukhanina O. Transforming growth factor-beta and breast cancer: lessons learned from genetically altered mouse models. Breast Canc Res. 2000;2(2):100–6.
Grainger DJ, Heathcote K, Chiano M, Snieder H, Kemp PR, Metcalfe JC, et al. Genetic control of the circulating concentration of transforming growth factor type β1. Hum Mol Genet. 1999;8:93–7.
Vaira D, Holton J, Cairns SR, Falzon M, Salman PR. Urease test for Helicobacter pylori. J Clin Pathol. 1988;41:355–6.
Lahiri D, Nurnberger J. A rapid non-enzymatic method for the preparation of HMW DNA from blood for RFLP studies. Nucleic Acids Res. 1991;19(19):5444.
Perrey C, Turner SJ, Pravica V, Howell WM, Hutchinson IV. ARM-SPCR methodologies to determine IL-10, TNF-α, TNF-β and TGF-β1 gene polymorphisms. Transplant Immunology. 1999;7(2):127–8.
Derynck R, Akhurst RJ, Balmain A. TGF-beta signaling in tumor suppression and cancer progression. Nat Genet. 2001;29(2):117–29.
Pulleyn LJ, Newton R, Adcock IM, Barnes PJ. TGFbeta1 allele association with asthma severity. Hum Genet. 2001;109(6):623–7.
Silverman ES, Palmer LJ, Subramaniam V, Hallock A, Mathew S, Vallone J, et al. Transforming growth factor-beta1 promoter polymorphism C-509T is associated with asthma. Am J Respir Crit Care Med. 2004;169(2):214–9.
Lin Y, Kikuchi S, Obata Y, Yagyu K, The Tokyo Research Group on Prevention of Gastric Cancer. Serum levels of transforming growth factor β1 are significantly correlated with venous invasion in patients with gastric cancer. J Gastroenterol Hepatol. 2006;21(2):432–7.
Hawinkels LJAC, Verspaget HW, Wvan Duijn JM, van der Zon ZK, Kubben FJGM, Verheijen JH, et al. Tissue level, activation and cellular localisation of TGF-β1 and association with survival in gastric cancer patients. Br J Canc. 2007;97:398–404.
Yoshida K, Yokozaki H, Niimoto M, Ito H, Ito M, Tahara E. Expression of TGF-beta and procollagen type I and type III in human gastric carcinomas. Int J Canc. 1989;44(3):394–8.
Shu XO, Gao YT, Cai Q, Pierce L, Cai H, Ruan ZX, et al. Genetic polymorphisms in the TGF-beta 1 gene and breast cancer survival: a report from the Shanghai. Breast Cancer Study. Canc Res. 2004;64(3):836–9.
Dunning AM, Ellis PD, McBride S, Kirschenlohr HL, Healey CS, Kemp PR, et al. A transforming growth factor beta1 signal peptide variant increases secretion in vitro and is associated with increased incidence of invasive breast cancer. Canc Res. 2003;63(10):2610–5.
Lundberg M, Pajusto M, Koskinen WJ, Makitie AA, Aaltonen LM, Mattila PS. Association between transforming growth factor beta1 genetic polymorphism and response to chemoradiotherapy in head and neck squamous cell cancer. Head Neck. 2009;31(5):664–72.
Kang HG, Chae MH, Park JM, Kim EJ, Park JH, Kam S, et al. Polymorphisms in TGF-beta1 gene and the risk of lung cancer. Lung Cancer. 2006;52(1):1–7.
Zhang P, Di JZ, Zhu ZZ, Wu HM, Wang Y, Zhu G, et al. Association of transforming growth factor-beta 1 polymorphisms with genetic susceptibility to TNM stage I or II gastric cancer. Jpn J Clin Oncol. 2008;38(12):861–6.
Li T, Cao B-W, Dai Y, Cui H, Yang Hong-Li, Chang-Qing Xu. Correlation of transforming growth factor beta-1 gene polymorphisms C-509T and T869C and the risk of gastric cancer in China. J Gastroenterol Hepatol. 2008;23(4):638–42.
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Financial support from Council for Scientific and Industrial Research (CSIR) is kindly acknowledged.
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Bhayal, A.C., Prabhakar, B., Rao, K.P.R. et al. Role of transforming growth factor-β1 −509 C/T promoter polymorphism in gastric cancer in south Indian population. Tumor Biol. 32, 1049–1053 (2011). https://doi.org/10.1007/s13277-011-0208-z
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DOI: https://doi.org/10.1007/s13277-011-0208-z