Molecular Biology Reports

, Volume 40, Issue 10, pp 5791–5796 | Cite as

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

  • Leizhen Zheng
  • Chen Zhu
  • Jianchun Gu
  • Pan Xi
  • Jiangbo Du
  • Guangfu Jin


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.


MUC1 Polymorphism rs4072037 Gastric cancer GWAS 


Conflict of interest



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).


  1. 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):1893–1907PubMedCrossRefGoogle Scholar
  2. 2.
    Shin A, Kim J, Park S (2011) Gastric cancer epidemiology in Korea. J Gastric Cancer 11(3):135–140PubMedCrossRefGoogle Scholar
  3. 3.
    Bouvard V, Baan R, Straif K et al (2009) A review of human carcinogens—part B. Lancet Oncol 10(4):321–322PubMedCrossRefGoogle Scholar
  4. 4.
    Secretan B, Straif K, Baan R et al (2009) A review of human carcinogens—part E. Lancet Oncol 10(11):1033–1034PubMedCrossRefGoogle Scholar
  5. 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):1289–1293PubMedCrossRefGoogle Scholar
  6. 6.
    Kusters JG, van Vliet AH, Kuipers EJ (2006) Pathogenesis of Helicobacter pylori infection. Clin Microbiol Rev 19(3):449–490PubMedCrossRefGoogle Scholar
  7. 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):224–228PubMedCrossRefGoogle Scholar
  8. 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):792–796PubMedCrossRefGoogle Scholar
  9. 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):730–740PubMedCrossRefGoogle Scholar
  10. 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):1131–1138PubMedCrossRefGoogle Scholar
  11. 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):435–441PubMedCrossRefGoogle Scholar
  12. 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):764–767PubMedCrossRefGoogle Scholar
  13. 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):848–852PubMedCrossRefGoogle Scholar
  14. 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):892–902PubMedCrossRefGoogle Scholar
  15. 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):313–321PubMedCrossRefGoogle Scholar
  16. 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):1313–1320PubMedGoogle Scholar
  17. 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-634Google Scholar
  18. 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):1215–1218PubMedCrossRefGoogle Scholar
  19. 19.
    Ng W, Loh AX, Teixeira AS et al (2008) Genetic regulation of MUC1 alternative splicing in human tissues. Br J Cancer 99(6):978–985PubMedCrossRefGoogle Scholar
  20. 20.
    Hollingsworth MA, Swanson BJ (2004) Mucins in cancer: protection and control of the cell surface. Nat Rev Cancer 4(1):45–60PubMedCrossRefGoogle Scholar
  21. 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):e1000617PubMedCrossRefGoogle Scholar
  22. 22.
    Singh PK, Hollingsworth MA (2006) Cell surface-associated mucins in signal transduction. Trends Cell Biol 16(9):467–476PubMedCrossRefGoogle Scholar
  23. 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):12492–12494PubMedCrossRefGoogle Scholar
  24. 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):4000–4003PubMedGoogle Scholar
  25. 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):13057–13064PubMedCrossRefGoogle Scholar
  26. 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):2313–2324PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  1. 1.Department of OncologyXin Hua Hospital Affiliated to Shanghai Jiaotong University School of MedicineShanghaiChina
  2. 2.Department of Epidemiology and Biostatistics and Ministry of Education Key Laboratory for Modern Toxicology, School of Public HealthNanjing Medical UniversityNanjingChina
  3. 3.Section of Clinical Epidemiology, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer CenterNanjing Medical UniversityNanjingChina

Personalised recommendations