Abstract
TP53 (TP53 Arg72Pro) gene polymorphisms at codon 72 have been associated with risk and susceptibility to various cancers. In this case-control study we examined the genotype distribution of TP53 Arg72Pro single nucleotide polymorphisms (SNP) by using a PCR-RFLP approach to determine that if this SNP can modulate the risk factor for gastric cancer development and to check for the possible correlation of this SNP with clinicopathological variables of gastric cancer. We in this study investigated the genotype distribution of this SNP in 120 gastric cancer cases in comparison with 170 healthy subjects. We found significant association of the Pro/Pro mutant related to clinical tumor stage (p=0.000164), lymph node involvement (p=0.00193), Age (p=0.00568) and EGD biopsy (p= 0.0097), but not to other variables. We by these investigations conclude that Arg72Pro SNP is associated with susceptibility to developing gastric cancer and lymph node development in ethnic Kashmiri population.
Keywords: Gastric cancer,Kashmiri population, SNP (single nucleotide polymorphism), TP53.
References
- Khuroo, M.S., et al., High incidence of oesophageal and gastric cancer in Kashmir in a population with special personal and dietary habits. Gut, 1992. 33(1): p. 11-15.
- Fuchs, C.S. and R.J. Mayer, Gastric Carcinoma. New England Journal of Medicine, 1995. 333(1): p. 32-41.
- Green, S., et al., Human oestrogen receptor cDNA: sequence, expression and homology to v-erb-A. Nature, 1986. 320(6058): p. 134-139.
- Levine, A.J., J. Momand, and C.A. Finlay, The p53 tumour suppressor gene. Nature, 1991. 351(6326): p. 453-456.
- Clarke, A.R., et al., Thymocyte apoptosis induced by p53-dependent and independent pathways. Nature, 1993. 362(6423): p. 849-852.
- Lowe, S., et al., p53 status and the efficacy of cancer therapy in vivo. Science, 1994. 266(5186): p. 807-810.
- Hulleman, E. and J. Boonstra*, Regulation of G1 phase progression by growth factors and the extracellular matrix. Cellular and Molecular Life Sciences, 2001. 58(1): p. 80-93.
- Zhou, R., et al., A role for mitochondria in NLRP3 inflammasome activation. 469(7329): p. 221-225.
- Kastan, M.B., et al., A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia. Cell, 1992. 71(4): p. 587-597.
- Kinzler, K.W. and B. Vogelstein, Cancer Therapy Meets p53. New England Journal of Medicine, 1994. 331(1): p. 49-50.
- Lowe, S.W., et al., p53 is required for radiation-induced apoptosis in mouse thymocytes. Nature, 1993. 362(6423): p. 847-849.
- Sameer, A.S., et al., TP53 Pro47Ser and Arg72Pro polymorphisms and colorectal cancer predisposition in an ethnic Kashmiri population. Genetics and Molecular Research. 9(2): p. 651-660.
- Abdullah, S., et al., P53- The Molecular Guardian Crashes in Gastric Adenocarcinomas - A Study in an Ethnic Kashmiri Population. Journal of Carcinogenesis & Mutagenesis. 01(02).
- Hiyama, T., et al., p53 Codon 72 polymorphism in gastric cancer susceptibility in patients withHelicobacter pylori-associated chronic gastritis. International Journal of Cancer, 2002. 100(3): p. 304-308.
- Irarrazabal, C., Chilean pilot study on the risk of lung cancer associated with codon 72 polymorphism in the gene of protein p53. Toxicology Letters, 2003. 144(1): p. 69-76.
- Commentaire du travail de Lee YJ et al., pp. 1018. 47(11): p. 1065-1065.
- Thomas, C.G., et al., Estrogen receptor beta decreases survival of p53-defective cancer cells after DNA damage by impairing G2/M checkpoint signaling. Breast Cancer Research and Treatment. 127(2): p. 417-427.
- Zhu, Z.-Z., et al., Association of the TP53 Codon 72 Polymorphism with Colorectal Cancer in a Chinese Population. Japanese Journal of Clinical Oncology, 2007. 37(5): p. 385-390.
- Frasor, J., et al., Gene Expression Preferentially Regulated by Tamoxifen in Breast Cancer Cells and Correlations with Clinical Outcome. Cancer Research, 2006. 66(14): p. 7334-7340.
- Koff, R.S., Textbook of gastroenterology. Edited by T. Yamada, D.H. Alpers, C. Owyang, D.W. Powell and F.E. Silverstein, 2,683 pp. Philadelphia: J. B. Lippincott, 1991. $180. Hepatology, 1992. 15(3): p. 559-560.
- Thomas, M., et al., Two Polymorphic Variants of Wild-Type p53 Differ Biochemically and Biologically. Molecular and Cellular Biology, 1999. 19(2): p. 1092-1100.
- Dumont, P., et al., The codon 72 polymorphic variants of p53 have markedly different apoptotic potential. Nature Genetics, 2003. 33(3): p. 357-365.
- Siddique, M.M., Evidence for Selective Expression of the p53 Codon 72 Polymorphs: Implications in Cancer Development. Cancer Epidemiology Biomarkers & Prevention, 2005. 14(9): p. 2245-2252.
- Devesa, S.S. and W.-H. Chow, Variation in colorectal cancer incidence in the united states by subsite of origin. Cancer, 1993. 71(12): p. 3819-3826.
- Gapstur, S.M., J.D. Potter, and A.R. Folsom, Alcohol Consumption and Colon and Rectal Cancer in Postmenopausal Women. International Journal of Epidemiology, 1994. 23(1): p. 50-57.
- Murtaza, I., A study on p53 gene alterations in esophageal squamous cell carcinoma and their correlation to common dietary risk factors among population of the Kashmir valley. World Journal of Gastroenterology, 2006. 12(25): p. 4033.
- Siddiqi, M., et al., Increased exposure to dietary amines and nitrate in a population at high risk of oesophageal and gastric cancer in Kashmir (India). Carcinogenesis, 1992. 13(8): p. 1331-1335.
Corresponding Author
Prof. Mushtaq A. Siddiq
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DOI: https://dx.doi.org/10.18535/jmscr/v7i2.151
