Abstract
Esophageal carcinoma (EC) is a common malignancy worldwide. Previous studies indicated that gastrointestinal gland cancer and EC share some susceptibility loci. Our aim was to identify new single nucleotide polymorphisms (SNPs) associated with EC by investigating whether known gastrointestinal cancers susceptibility loci are found in EC patients. A Chinese Han population case–control study was conducted to assess SNP associations with EC risk. Twenty-six SNPs were selected from gastrointestinal cancer susceptibility loci, and 360 EC patients and 310 controls were genotyped for these SNPs using Sequenom MassARRAY technology. The association of SNP frequencies with EC was analyzed by chi-square tests, and genetic model analysis. After Hardy–Weinberg equilibrium (HWE) p value screening, we excluded two SNPs. Based on chi-square tests, the minor alleles of rs13294589 (p = 0.046) and rs4924935 (p = 0.046) were correlated with reduced EC risk and rs4269383 (p = 0.010) and rs10953615 (p = 0.036) were correlated with increased EC risk. In the genetic model analyses, we found that the minor alleles “T” of rs401681, “A” of rs10088262, and “C” of rs4924935 may reduce the risk of EC. rs401681 has previously been reported to be associated with EC. To the best of our knowledge, we are the first to report an association of the other five SNPs with EC. Our findings provide evidence for the genetic variants associated with susceptibility to EC in the Chinese Han population, which might be used as potential molecular markers for detecting susceptibility to EC in Chinese Han people.
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Xu X, Guan X, Tao H, Yang K, Bai Y. An association study on genetic polymorphisms of Rab37 gene with the risk of esophageal squamous cell carcinoma in a Chinese Han population. Int J Med Sci. 2013;10(3):235–42. doi:10.7150/ijms.5524.
Bray F, Ren JS, Masuyer E, Ferlay J. Global estimates of cancer prevalence for 27 sites in the adult population in 2008. Int J Cancer J Int Du Cancer. 2013;132(5):1133–45. doi:10.1002/ijc.27711.
Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer J int Du Cancer. 2015;136(5):E359–86. doi:10.1002/ijc.29210.
Chen W, Zheng R, Zhang S, Zeng H, Fan Y, Qiao Y et al. Esophageal cancer incidence and mortality in China, 2010. Thoracic Cancer. 2014.
Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127(12):2893–917. doi:10.1002/ijc.25516.
Schottenfeld D, Fraumeni Jr JF. Cancer epidemiology and prevention. Eastbourne, UK; WB Saunders Co; 1982.
Lagergren J, Bergström R, Lindgren A, Nyren O. The role of tobacco, snuff and alcohol use in the aetiology of cancer of the oesophagus and gastric cardia. Int J Cancer. 2000;85(3):340–6.
Wu M, Zhao J-K, Zhang Z-F, Han R-Q, Yang J, Zhou J-Y, et al. Smoking and alcohol drinking increased the risk of esophageal cancer among Chinese men but not women in a high-risk population. Cancer Causes Control. 2011;22(4):649–57.
Gao Y, Hu N, Han XY, Ding T, Giffen C, Goldstein AM, et al. Risk factors for esophageal and gastric cancers in Shanxi Province, China: a case–control study. Cancer Epidemiol. 2011;35(6):e91–e9.
LaFramboise T, Weir BA, Zhao X, Beroukhim R, Li C, Harrington D, et al. Allele-specific amplification in cancer revealed by SNP array analysis. PLoS Comput Biol. 2005;1(6):e65. doi:10.1371/journal.pcbi.0010065.
Lerand SJ, Ireland M, Blum RW. Individual and environmental impacts on sexual health of Caribbean youth. The Scientific World Journal. 2006;6:707–17. doi:10.1100/tsw.2006.150.
Wu C, Hu Z, He Z, Jia W, Wang F, Zhou Y, et al. Genome-wide association study identifies three new susceptibility loci for esophageal squamous-cell carcinoma in Chinese populations. Nat Genet. 2011;43(7):679–84. doi:10.1038/ng.849.
Ek WE, Levine DM, D’Amato M, Pedersen NL, Magnusson PK, Bresso F, et al. Germline genetic contributions to risk for esophageal adenocarcinoma, Barrett’s esophagus, and gastroesophageal reflux. J Natl Cancer Inst. 2013;105(22):1711–8. doi:10.1093/jnci/djt303.
Li S, Qian J, Yang Y, Zhao W, Dai J, Bei JX, et al. GWAS identifies novel susceptibility loci on 6p21.32 and 21q21.3 for hepatocellular carcinoma in chronic hepatitis B virus carriers. PLoS Genet. 2012;8(7):e1002791. doi:10.1371/journal.pgen.1002791.
Low SK, Kuchiba A, Zembutsu H, Saito A, Takahashi A, Kubo M, et al. Genome-wide association study of pancreatic cancer in Japanese population. PLoS One. 2010;5(7):e11824. doi:10.1371/journal.pone.0011824.
Wu L, Goldstein AM, Yu K, Yang XR, Rabe KG, Arslan AA, et al. Variants associated with susceptibility to pancreatic cancer and melanoma do not reciprocally affect risk. Cancer Epidemiol Biomarkers Prev. 2014;23(6):1121–4. doi:10.1158/1055-9965.EPI-13-0627.
Campa D, Rizzato C, Bauer AS, Werner J, Capurso G, Costello E, et al. Lack of replication of seven pancreatic cancer susceptibility loci identified in two Asian populations. Cancer Epidemiol Biomarkers Prev. 2013;22(2):320–3. doi:10.1158/1055-9965.EPI-12-1182.
Wu C, Miao X, Huang L, Che X, Jiang G, Yu D, et al. Genome-wide association study identifies five loci associated with susceptibility to pancreatic cancer in Chinese populations. Nat Genet. 2012;44(1):62–6. doi:10.1038/ng.1020.
Wu C, Kraft P, Stolzenberg-Solomon R, Steplowski E, Brotzman M, Xu M, et al. Genome-wide association study of survival in patients with pancreatic adenocarcinoma. Gut. 2014;63(1):152–60. doi:10.1136/gutjnl-2012-303477.
Petersen GM, Amundadottir L, Fuchs CS, Kraft P, Stolzenberg-Solomon RZ, Jacobs KB, et al. A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Nat Genet. 2010;42(3):224–8. doi:10.1038/ng.522.
Cha PC, Zembutsu H, Takahashi A, Kubo M, Kamatani N, Nakamura Y. A genome-wide association study identifies SNP in DCC is associated with gallbladder cancer in the Japanese population. J Hum Genet. 2012;57(4):235–7. doi:10.1038/jhg.2012.9.
Yang Q, Guo CY, Cupples LA, Levy D, Wilson PW, Fox CS. Genome-wide search for genes affecting serum uric acid levels: the Framingham Heart Study. Metabolism. 2005;54(11):1435–41. doi:10.1016/j.metabol.2005.05.007.
Gabriel S, Ziaugra L, Tabbaa D. SNP genotyping using the Sequenom MassARRAY iPLEX platform. Curr Protocols Human Genet. 2009:2.12. 1-2. 6.
Thomas RK, Baker AC, DeBiasi RM, Winckler W, LaFramboise T, Lin WM, et al. High-throughput oncogene mutation profiling in human cancer. Nat Genet. 2007;39(3):347–51.
Simon E. Chi2 test for two by two percentage comparison table. Gynecol Obstetrique Fertilite. 2009;37(1):95–6. doi:10.1016/j.gyobfe.2008.11.005.
Sole X, Guino E, Valls J, Iniesta R, Moreno V. SNPStats: a web tool for the analysis of association studies. Bioinformatics. 2006;22(15):1928–9. doi:10.1093/bioinformatics/btl268.
Bland JM, Altman DG. Statistics notes. The odds ratio. BMJ. 2000;320(7247):1468.
Barrett JC, Fry B, Maller J, Daly MJ. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics. 2005;21(2):263–5. doi:10.1093/bioinformatics/bth457.
Shi YY, He L. SHEsis, a powerful software platform for analyses of linkage disequilibrium, haplotype construction, and genetic association at polymorphism loci. Cell Res. 2005;15(2):97–8. doi:10.1038/sj.cr.7290272.
Yin J, Wang L, Zheng L, Wang X, Shi Y, Shao A, et al. TERT-CLPTM1L Rs401681 C>T polymorphism was associated with a decreased risk of esophageal cancer in a Chinese population. PLoS One. 2014;9(7):e100667. doi:10.1371/journal.pone.0100667.
Zhao DP, Yang CL, Zhou X, Ding JA, Jiang GN. Association between CLPTM1L polymorphisms (rs402710 and rs401681) and lung cancer susceptibility: evidence from 27 case-control studies. Mol Genet Genomics: MGG. 2014;289(5):1001–12. doi:10.1007/s00438-014-0868-7.
James MA, Wen W, Wang Y, Byers LA, Heymach JV, Coombes KR, et al. Functional characterization of CLPTM1L as a lung cancer risk candidate gene in the 5p15.33 locus. PLoS One. 2012;7(6):e36116. doi:10.1371/journal.pone.0036116.
Zhang Y, Sun Y, Chen T, Hu H, Xie W, Qiao Z, et al. Genetic variations rs11892031 and rs401681 are associated with bladder cancer risk in a Chinese population. Int J Mol Sci. 2014;15(11):19330–41. doi:10.3390/ijms151119330.
Liu C, Wang Y, Huang H, Wang C, Zhang H, Kong Y, et al. Association between CLPTM1L-TERT rs401681 polymorphism and pancreatic cancer risk among Chinese Han population. Tumour Biol. 2014;35(6):5453–7. doi:10.1007/s13277-014-1711-9.
Yamamoto-Ibusuki M, Yamamoto Y, Fujiwara S, Sueta A, Yamamoto S, Hayashi M, et al. C6ORF97-ESR1 breast cancer susceptibility locus: influence on progression and survival in breast cancer patients. Eur J Human Genet: EJHG. 2014. doi:10.1038/ejhg.2014.219.
Acknowledgments
This work is supported by the National 863 High-Technology Research and Development Program (No. 2012AA02A519). We are grateful to the patients and control subjects for their participation in this study. We also thank the clinicians and hospital staff who contributed to the sample and data collection for this study. For sample collection, we thank the First Affiliated Hospital of Xi’an Jiaotong University and Tangdu Hospital for their assistance. We would also like to thank the BioScience Writers for their assistance in the preparation of this manuscript.
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Junqi Wang and Baoping Zhang are joint first authors.
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Wang, J., Zhang, B., Yang, Z. et al. Association of gastrointestinal gland cancer susceptibility loci with esophageal carcinoma among the Chinese Han population: a case–control study. Tumor Biol. 37, 1627–1633 (2016). https://doi.org/10.1007/s13277-015-3945-6
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DOI: https://doi.org/10.1007/s13277-015-3945-6