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Functional polymorphism rs4072037 in MUC1 gene contributes to the susceptibility to gastric cancer: evidence from pooled 6,580 cases and 10,324 controls

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Abstract

Genome-wide association studies have reported a promising association of rs4072037 with gastric cancer (GC). This variant was associated with altered physiological function of MUC1 possibly by modulating promoter activity and alternative splicing of MUC1. However, the association results were inconclusive and estimate of the effect of this variant was not well evaluated. A meta-analysis by systematically reviewing relevant reports may facilitate to address these concerns. Association studies involving MUC1 rs4072037 polymorphism and GC risk were identified up to June 30, 2012. Odds ratio (OR) and 95 % confidence interval (CI) in additive model were estimated or extracted from each study. The pooled effect size was quantitatively synthesized using meta-analysis. Heterogeneity between studies was measured by the Q test and I 2 statistic, and publication bias was evaluated by a funnel plot and the Egger’s test. A total of 10 independent case–control studies including 6,580 GC cases and 10,324 controls were included in this meta-analysis. Eight of the ten studies were Asian ethnicity and two European. The G allele of MUC1 rs4072037 was significantly associated with a decreased risk of GC (OR = 0.72, 95 % CI 0.68–0.77; P = 7.82 × 10−25), as compared with A allele. Stratification for different ethnicity, tumor localization or type showed similar results. These findings represent important evidence for association of MUC1 rs4072037 variant with GC risk, and also provide a relatively reliable estimate of effect size. MUC1 is a strong candidate as a susceptibility gene of GC.

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References

  1. Jemal A, Center MM, DeSantis C et al (2010) Global patterns of cancer incidence and mortality rates and trends. Cancer Epidemiol Biomarkers Prev 19(8):1893–1907

    Article  PubMed  Google Scholar 

  2. Shin A, Kim J, Park S (2011) Gastric cancer epidemiology in Korea. J Gastric Cancer 11(3):135–140

    Article  PubMed  Google Scholar 

  3. Bouvard V, Baan R, Straif K et al (2009) A review of human carcinogens—part B. Lancet Oncol 10(4):321–322

    Article  PubMed  Google Scholar 

  4. Secretan B, Straif K, Baan R et al (2009) A review of human carcinogens—part E. Lancet Oncol 10(11):1033–1034

    Article  PubMed  Google Scholar 

  5. Kim J, Park S, Nam BH (2010) Gastric cancer and salt preference: a population-based cohort study in Korea. Am J Clin Nutr 91(5):1289–1293

    Article  PubMed  CAS  Google Scholar 

  6. Kusters JG, van Vliet AH, Kuipers EJ (2006) Pathogenesis of Helicobacter pylori infection. Clin Microbiol Rev 19(3):449–490

    Article  PubMed  CAS  Google Scholar 

  7. Petersen GM, Amundadottir L, Fuchs CS et al (2010) A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Nat Genet 42(3):224–228

    Article  PubMed  CAS  Google Scholar 

  8. Hu Z, Wu C, Shi Y et al (2011) A genome-wide association study identifies two new lung cancer susceptibility loci at 13q12.12 and 22q12.2 in Han Chinese. Nat Genet 43(8):792–796

    Article  PubMed  CAS  Google Scholar 

  9. Sakamoto H, Yoshimura K, Saeki N et al (2008) Genetic variation in PSCA is associated with susceptibility to diffuse-type gastric cancer. Nat Genet 40(6):730–740

    Article  PubMed  CAS  Google Scholar 

  10. Wu C, Wang G, Yang M et al (2009) Two genetic variants in prostate stem cell antigen and gastric cancer susceptibility in a Chinese population. Mol Carcinog 48(12):1131–1138

    Article  PubMed  CAS  Google Scholar 

  11. Lochhead P, Frank B, Hold GL et al (2011) Genetic variation in the prostate stem cell antigen gene and upper gastrointestinal cancer in white individuals. Gastroenterology 140(2):435–441

    Article  PubMed  CAS  Google Scholar 

  12. Abnet CC, Freedman ND, Hu N et al (2010) A shared susceptibility locus in PLCE1 at 10q23 for gastric adenocarcinoma and esophageal squamous cell carcinoma. Nat Genet 42(9):764–767

    Article  PubMed  CAS  Google Scholar 

  13. Zhang H, Jin G, Li H et al (2011) Genetic variants at 1q22 and 10q23 reproducibly associated with gastric cancer susceptibility in a Chinese population. Carcinogenesis 32(6):848–852

    Article  PubMed  CAS  Google Scholar 

  14. Saeki N, Saito A, Choi IJ et al (2011) A functional single nucleotide polymorphism in mucin 1, at chromosome 1q22, determines susceptibility to diffuse-type gastric cancer. Gastroenterology 140(3):892–902

    Article  PubMed  CAS  Google Scholar 

  15. Jia Y, Persson C, Hou L et al (2010) A comprehensive analysis of common genetic variation in MUC1, MUC5AC, MUC6 genes and risk of stomach cancer. Cancer Causes Control 21(2):313–321

    Article  PubMed  Google Scholar 

  16. Xu Q, Yuan Y, Sun LP et al (2009) Risk of gastric cancer is associated with the MUC1 568 A/G polymorphism. Int J Oncol 35(6):1313–1320

    PubMed  CAS  Google Scholar 

  17. Palmer AJ, Lochhead P, Hold GL et al (2012) Mo1584 genetic variation in C20orf54, PLCE1 and MUC1 and risk of upper gastrointestinal cancers in Caucasian populations. Gastroenterology 142(Supplement 1):S-634

    Google Scholar 

  18. Shi Y, Hu Z, Wu C et al (2011) A genome-wide association study identifies new susceptibility loci for non-cardia gastric cancer at 3q13.31 and 5p13.1. Nat Genet 43(12):1215–1218

    Article  PubMed  CAS  Google Scholar 

  19. Ng W, Loh AX, Teixeira AS et al (2008) Genetic regulation of MUC1 alternative splicing in human tissues. Br J Cancer 99(6):978–985

    Article  PubMed  CAS  Google Scholar 

  20. Hollingsworth MA, Swanson BJ (2004) Mucins in cancer: protection and control of the cell surface. Nat Rev Cancer 4(1):45–60

    Article  PubMed  CAS  Google Scholar 

  21. Linden SK, Sheng YH, Every AL et al (2009) MUC1 limits Helicobacter pylori infection both by steric hindrance and by acting as a releasable decoy. PLoS Pathog 5(10):e1000617

    Article  PubMed  Google Scholar 

  22. Singh PK, Hollingsworth MA (2006) Cell surface-associated mucins in signal transduction. Trends Cell Biol 16(9):467–476

    Article  PubMed  CAS  Google Scholar 

  23. Yamamoto M, Bharti A, Li Y et al (1997) Interaction of the DF3/MUC1 breast carcinoma-associated antigen and beta-catenin in cell adhesion. J Biol Chem 272(19):12492–12494

    Article  PubMed  CAS  Google Scholar 

  24. Pandey P, Kharbanda S, Kufe D (1995) Association of the DF3/MUC1 breast cancer antigen with Grb2 and the Sos/Ras exchange protein. Cancer Res 55(18):4000–4003

    PubMed  CAS  Google Scholar 

  25. Schroeder JA, Thompson MC, Gardner MM et al (2001) Transgenic MUC1 interacts with epidermal growth factor receptor and correlates with mitogen-activated protein kinase activation in the mouse mammary gland. J Biol Chem 276(16):13057–13064

    Article  PubMed  CAS  Google Scholar 

  26. McAuley JL, Linden SK, Png CW et al (2007) MUC1 cell surface mucin is a critical element of the mucosal barrier to infection. J Clin Invest 117(8):2313–2324

    Article  PubMed  CAS  Google Scholar 

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Funding

This study was supported by the Jiangsu Natural Science Foundation (BK2012841, BK20130042), the National Natural Science Foundation of China (81001276, 81373090), the National Key Basic Research Program Grant (2013CB910304), and the Priority Academic Program for the Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine).

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Correspondence to Leizhen Zheng or Guangfu Jin.

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Leizhen Zheng and Chen Zhu contributed equally to this study.

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Zheng, L., Zhu, C., Gu, J. et al. Functional polymorphism rs4072037 in MUC1 gene contributes to the susceptibility to gastric cancer: evidence from pooled 6,580 cases and 10,324 controls. Mol Biol Rep 40, 5791–5796 (2013). https://doi.org/10.1007/s11033-013-2682-4

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  • DOI: https://doi.org/10.1007/s11033-013-2682-4

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