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Association of mismatch repair gene polymorphism with susceptibility to sporadic colorectal cancer in Tianjin region

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  • 1. Department of Anus & Intestine Surgery, Tianjin People’s Hospital, Tianjin 300121, China; 
    2. Tianjin Medical College, Tianjin 300222, China; 
    3. Department of Clinical Laboratory, Tianjin People’s Hospital, Tianjin 300121, China

Received date: 2010-02-09

  Revised date: 2010-04-26

  Online published: 2010-12-20

Abstract

To investigate the possible association of mismatch repair gene single nucleotide polymorphisms (SNPs) with susceptibility to sporadic colorectal cancer (SCRC), the genotypes of hMLH1 394G/C, hMSH2 943-1G/A, hMSH2 1917T/G, and hMSH2 2783C/A were detected by PCR-denaturing high-performance liquid chromatography (DHPLC) in 600 SCRC patients and 600 healthy controls. The genotype distribution of hMSH2 2783C/A in SCRC patients (90%, 9%, and 1%) was significantly different from that in the controls (95%, 4.8%, and 0.23%; χ2=11.91, P<0.01). Compared to hMSH2 2783C/C, genotypes C/A and A/A significantly increased the risk of developing SCRC (OR were 1.77 and 11.94, and the reanges of 95% CI were 1.03-3.03 and 1.38-103.2). When combined analysis of three SNPs was performed, the haplotype distribution in SCRC patients was significantly different from that in controls (χ2=38.38, P<0.01). In reference to 394G/943-1G /2783C haplotype, 394G/943-1G /2783A haplotype contributed significantly to SCRC (OR=2.18, 95% CI: 1.40-3.40). These results indicate that hMSH2 2783C/A polymorphism has potential to be a susceptibility factor for SCRC and the 394G/943-1G /2783A haplotype might increase the risk of developing SCRC.

Cite this article

LI Hui-Chen, FENG Hui-Yuan, ZHANG Ti-Peng, LIU Juan, MA Dong-Wang, QIN Hai, ZHOU Yi, SHU Lin . Association of mismatch repair gene polymorphism with susceptibility to sporadic colorectal cancer in Tianjin region[J]. Hereditas(Beijing), 2010 , 32(12) : 1241 -1246 . DOI: 10.3724/SP.J.1005.2010.01241

References

[1] Mohrenweiser HW, Jones IM. Variation in DNA repair is a factor in cancer susceptibility: a paradigm for the promises and perils of individual and population risk estimation? Mutat Res, 1998, 400(1–2): 15–24. [2] Knudson AG. Hereditary predisposition to cancer. Ann N Y Acad Sci, 1997, 833(1): 58–67. [3] Scartozzi M, Bianchi F, Rosati S, Galizia E, Antolini A, Loretelli C, Piga A, Bearzi I, Cellerino R, Porfiri E. Muta-tions of hMLH1 and hMSH2 in patients with suspected hereditary nonpolyposis colorectal cancer: correlation with microsatellite instability and abnormalities of mis-match repair protein expression. J Clin Oncol, 2002, 20(5): 1203–1208. [4] Liu B, Parsons R, Papadopoulos N, Nicolaides NC, Lynch HT, Watson P, Jass JR, Dunlop M, Wyllie A, Peltomäki P, de la Chapelle A, Hamilton SR, Vogelstein B, Kinzler KW. Analysis of mismatch repair genes in hereditary non-polyposis colorectal cancer patients. Nat Med, 1996, 2(2): 169–174. [5] Mitchell RJ, Farrington SM, Dunlop MG, Campbell H. Mismatch repair genes hMLH1 and hMSH2 and colorectal cancer: a HuGE review. Am J Epidemiol, 2002, 156(10): 885–902. [6] Kim JC, Roh SA, Koo KH, Ka IH, Kim HC, Yu CS, Lee KH, Kim JS, Lee H I, Bodmer WF. Genotyping possible polymorphic variants of human mismatch repair genes in healthy Korean individuals and sporadic colorectal cancer patients. Fam Cancer, 2004, 3(2): 129–137. [7] Lipkin SM, Rozek LS, Rennert G, Yang W, Chen PC, Ha-cia J, Hunt N, Shin B, Fodor S, Kokoris M, Greenson J K, Fearon E, Lynch H, Collins F, Gruber SB. The MLH1 D132H variant is associated with susceptibility to sporadic colorectal cancer. Nat Genet, 2004, 36(7): 694–699. [8] Shin BY, Chen HP, Rozek LS, Paxton L, Peel DJ, An-ton-Culver H, Rennert G, Mutch DG, Goodfellow PJ, Gruber SB, Lipkin SM. Low allele frequency of MLH1 D132H in American colorectal and endometrial cancer pa-tients. Dis Colon Rectum, 2005, 48(9): 1723–1727. [9] Palicio M, Blanco I, Tórtola S, González I, Marcuello E, Brunet J, Lluis F, González-Aguilera JJ, Peinado MA, Capella G. Intron splice acceptor site polymorphism in the hMSH2 gene in sporadic and familial colorectal cancer. Br J Cancer, 2000, 82(3): 535–537. [10] Nejda N, Iglesias D, Moreno Azcoita M, Medina Arana V, Gonzalez-Aguilera JJ, Fernandez-Peralta AM. A MLH1 polymorphism that increases cancer risk is associated with better outcome in sporadic colorectal cancer. Cancer Genet Cytogenet, 2009, 193(2): 71–77. [11] Koessler T, Oestergaard MZ, Song H, Tyrer J, Perkins B, Dunning AM, Easton DF, Pharoah PD. Common variants in mismatch repair genes and risk of colorectal cancer. Gut, 2008, 57(8): 1097–1101. [12] Schafmayer C, Buch S, Egberts JH, Franke A, Brosch M, El Sharawy A, Conring M, Koschnick M, Schwiedernoch S, Katalinic A, Kremer B, Fölsch UR, Krawczak M, Fän- drich F, Schreiber S, Tepel J, Hampe J. Genetic investiga-tion of DNA-repair pathway genes PMS2, MLH1, MSH2, MSH6, MUTYH, OGG1 and MTH1 in sporadic colon cancer. Int J Cancer, 2007, 121(3): 555–558. [13] Mei Q, Yan HL, Ding FX, Xue G, Huang JJ, Wang YZ, Sun SH. Single-nucleotide polymorphisms of mismatch repair genes in healthy Chinese individuals and sporadic colorectal cancer patients. Cancer Genet Cytogenet, 2006, 171(1): 17–23. [14] Feigelson HS, Cox DG, Cann HM, Wacholder S, Kaaks R, Henderson BE, Albanes D, Altshuler D, Berglund G, Ber-rino F, Bingham S, Buring JE, Burtt NP, Calle EE, Chanock SJ, Clavel-Chapelon F, Colditz G, Diver WR, Freedman ML, Haiman CA, Hankinson SE, Hayes RB, Hirschhorn JN, Hunter D, Kolonel LN, Kraft P, LeMar-chand L, Linseisen J, Modi W, Navarro C, Peeters PH, Pike MC, Riboli
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