Abstract
Introduction PARP-1 plays important role in the BER (base excision repair) and maintenance of genomic integrity. Previous study found the Val762Ala genetic variant in the PARP-1 gene contributed to susceptibility of some cancers and decreased PARP-1 enzyme activity in response to oxidative damage. Helicobacter pylori (H. pylori) infection was thought to be one of the major causes of gastric cancer. In this study, we investigated the association between the PARP-1 Val762Ala polymorphism, CagA+ H. pylori infection, and the risk for gastric cancer. Methods This hospital-based, case–control study was performed involving 556 individuals (236 cases with gastric cancer and 320 controls without evidence of neoplasm and gastrointestinal disease) using a PCR-RFLP method. Chi-square test and logistic regression analysis were used to count OR and 95% CI. Results 762Ala/Ala genotype was overrepresented in the cases (16.9%) compared with controls (10.3%), (OR, 1.942; 95% CI, 1.157–3.257, P = 0.011). Multivariate analysis showed that two factors were significantly associated with risk of gastric cancer, including CagA+ H. pylori infection (OR, 2.562; 95% CI, 1.174–5.240, P = 0.037), PARP-1 762AA genotype (OR, 1.772; 95% CI, 1.065–3.867; P = 0.042). Stratification analysis indicated that among Cag+ H. pylori positive subjects, 762Ala/Ala carriers had higher risk for developing gastric cancer compared with 762Val/Val carrier (OR, 2.337; 95% CI, 1.148–4.758; P = 0.017). Conclusion PARP-1 762Ala/Ala could be a risk factor for gastric cancer in Han Chinese population; PARP-1 762Val/Ala polymorphism and Cag+ H. pylori infection jointly contribute to higher risk for gastric cancer.
Similar content being viewed by others
References
Xiuti S, Ren M, Shangyou Z et al (2002) Analyses of gastric cancer mortality in China from 1990 to 1992. Chin J Oncol 24(1):4–8
Wood RD, Mitchell M, Sgouros J, Lindahl T (2001) Human DNA repair genes. Science 291:1284–1289. doi:10.1126/science.1056154
Wang Z-Q, Stingl L, Morrison C, Jantsch M, Los M, Schulze-Osthoff K, Wagner EF (1997) PARP is important for genomic stability but dispensable in apoptosis. Genes Dev 11:234–237
Süsse S, Scholz C-J, Bürkle A, Wiesmüller L (2004) Poly(ADP-ribose) polymerase (PARP-1) and p53 independently function in regulating double-strand break repair in primate cells. Nucleic Acids Res 32:669–680. doi:10.1093/nar/gkh227
Simbulan-Rosenthal CM, Haddad BR, Rosenthal DS, Weaver Z, Coleman A, Luo R, Young HM, Wang Z-Q, Ried T, Smulson ME (1999) Chromosomal aberrations in PARP−/−mice: genome stabilization in immortalized cells by reintroduction of poly(ADP-ribose) polymerase cDNA. Proc Natl Acad Sci USA 96:13191–13196. doi:10.1073/pnas.96.23.13191
Cottet F, Blanche H, Verasdonck P, Le Gall I, Schachter F, Burkle A et al (2000) New polymorphisms in the human poly(ADP-ribose) polymerase-1 coding sequence: lack of association with longevity or with increased cellular poly(ADP-ribosyl)ation capacity. J Mol Med 78(8):431–440. doi:10.1007/s001090050488
Kumari SR, Mendoza-Alvarez H, Alvarez-Gonzalez R (1998) Functional interactions of p53 with poly(ADP-ribose) polymerase (PARP) during apoptosis following DNA damage: covalent poly(ADP-ribosyl)ation of p53 by exogenous PARP and noncovalent binding of p53 to the Mr 85,000 proteolytic fragment. Cancer Res 58:5075–5078
Kim MY, Zhang T, Kraus WL (2005) Poly(ADP-ribosyl)ation by PARP-1: ‘PAR-laying’ NAD+ into a nuclear signal. Genes Dev 19:1951–1967. doi:10.1101/gad.1331805
Shiokawa M, Masutani M, Fujihara H, Ueki K, Nishikawa R, Sugimura T, Kubo H, Nakagama H (2005) Genetic alteration of poly(ADP-ribose)polymerase-1 in human germ cell tumors. Jpn J Clin Oncol 35:97–102. doi:10.1093/jjco/hyi028
Lockett KL, Hall MC, Xu J, Zheng SL, Berwick M, Chuang S-C, Clark PE, Cramer SD, Lohman K, Hu JJ (2004) The ADPRT V762A genetic variant contributes to prostate cancer susceptibility and deficient enzyme function. Cancer Res 64:6344–6348. doi:10.1158/0008-5472.CAN-04-0338
Zhang X, Miao X, Liang G, Hao B, Wang Y, Tan W, Li Y, Guo Y, He F, Wei Q, Lin D (2005) Polymorphisms in DNA base excision repair genes ADPRT and XRCC1 and risk of lung cancer. Cancer Res 65:722–726
Hao B, Wang H, Zhou K, Li Y, Chen X, Zhou G, Zhu Y, Miao X, Tan W, Wei Q, Lin D, He F (2004) Identification of genetic variants in base excision repair pathway and their associations with risk of esophageal squamous cell carcinoma. Cancer Res 64:4378–4384. doi:10.1158/0008-5472.CAN-04-0372
Blaser MJ, Chyou PH, Nomura A (1995) Age at establishment of Helicobacter pylori infection and gastric carcinoma, gastric ulcer, and duodenal ulcer risk. Cancer Res 55:562–565
Koehler CI, Mues MB, Dienes HP, Kriegsmann J, Schirmacher P, Odenthal M (2003) Helicobacter pylori genotyping in gastric adenocarcinoma and MALT lymphoma by multiplex PCR analyses of paraffin wax embedded tissues. Mol Pathol 56:36–42. doi:10.1136/mp.56.1.36
Forman D (1996) Helicobacter pylori and gastric cancer. Scand J Gastroenterol Suppl 220:23–26. doi:10.3109/00365529609094746
Moss SF, Sordillo EM, Abdalla AM, Makarov V, Hanzely Z, Perez-Perez GI, Blaser MJ, Holt PR (2001) Increased gastric epithelial cell apoptosis associated with colonization with CagA+ Helicobacter pylori strains. Cancer Res 61:1406–1411
Kidd M, Lastovica AJ, Atherton JC, Louw JA (2001) Conservation of the cag pathogenicity island is associated with vacA alleles and gastroduodenal disease in South African Helicobacter pylori isolates. Gut 49:11–17. doi:10.1136/gut.49.1.11
Figueiredo C, Quint W, Nouhan N, van den Munckhof H, Herbrink P, Scherpenisse J, de Boer W, Schneeberger P, Perez-Perez G, Blaser MJ, van Doorn L-J (2001) Assessment of Helicobacter pylori vacA and cagA Genotypes and Host Serological Response. JCM 39(4):1339–1344
Blaser MJ, Perez-Perez GI, Kleanthous H, Cover TL, Peek RM, Chyou PH, Stemmermann GN, Nomura A (1995) Infection with Helicobacter pylori strains possessing cagA is associated with an increased risk of developing adenocarcinoma of the stomach. Cancer Res 55:2111–2115
Parsonnet J, Friedman GD, Orentreich N, Vogelman H (1997) Risk for gastric cancer in people with CagA positive or CagA negative Helicobacter pylori infection. Gut 40:297–301
Huang JQ, Zheng GF, Sumanac K, Irvine EJ, Hunt RH (2003) Meta-analysis of the relationship between cagA seropositivity and gastric cancer. Gastroenterology 125(6):1636–1644. doi:10.1053/j.gastro.2003.08.033
Ohyauchi M, Imatani A, Yonechi M, Asano N, Miura A, Iijima K et al (2005) The polymorphism interleukin 8–251 A/T influences the susceptibility of Helicobacter pylori related gastric diseases in the Japanese population. Gut 54:330–335. doi:10.1136/gut.2003.033050
Yea SS, Yang YI, Jang WH, Lee YJ, Bae H-S, Paik K-H (2001) Association between TNF-αpromoter polymorphism and Helicobacter pylori cagA subtype infection. J Clin Pathol 54(9):703–706
Pieper AA, Blackshaw S, Clements EE, Brat DJ, Krug DK, White AJ, Pinto-Garcia P, Favit A, Conover JR, Snyder SH, Verma A (2000) Poly(ADP-ribosyl)ation basally activated by DNA strand breaks reflects glutamate–nitric oxide neurotransmission. Proc Natl Acad Sci USA 97(4):1845–1850. doi:10.1073/pnas.97.4.1845
Virag L, Szabo C (2002) The therapeutic potential of poly(ADP-Ribose) polymerase inhibitors. Pharmacol Rev 54:375–429. doi:10.1124/pr.54.3.375
Zhu Y, Spitz MR, Amos CI, Lin J, Schabath MB, Wu X (2004) Nucleotide polymorphism screening in molecular cancer epidemiology. Cancer Res 64(3):2251–2257. doi:10.1158/0008-5472.CAN-03-2800
Kim JJ, Tao H, Carloni E, Leung WK, Graham DY, Sepulveda AR (2002) Helicobacter pylori impairs DNA mismatch repair in gastric epilthelial cells. J Gastroenterol 123(2):542–553
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Zhang, Q., Li, Y., Li, X. et al. PARP-1 Val762Ala polymorphism, CagA+ H. pylori infection and risk for gastric cancer in Han Chinese population. Mol Biol Rep 36, 1461–1467 (2009). https://doi.org/10.1007/s11033-008-9336-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11033-008-9336-y