Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2008

Open Access 01-12-2008 | Research article

A novel diffuse gastric cancer susceptibility variant in E-cadherin (CDH1) intron 2: A case control study in an Italian population

Authors: Soroush Nasri, Helen More, Francesco Graziano, Annamaria Ruzzo, Emily Wilson, Anita Dunbier, Cushla McKinney, Tony Merriman, Parry Guilford, Mauro Magnani, Bostjan Humar

Published in: BMC Cancer | Issue 1/2008

Login to get access

Abstract

Background

Inherited genetic factors such as E-cadherin (CDH1) promoter variants are believed to influence the risk towards sporadic diffuse gastric cancer (DGC). Recently, a new regulatory region essential for CDH1 transcription has been identified in CDH1 intron 2.

Methods

We genotyped all known polymorphisms located within conserved sequences of CDH1 intron 2 (rs10673765, rs9932686, rs1125557, rs9282650, rs9931853) in an Italian population consisting of 134 DGC cases and 100 healthy controls (55 patient relatives and 45 unrelated, matched individuals). The influence of individual variants on DGC risk was assessed using χ2-tests and logistic regression. The relative contribution of alleles was estimated by haplotype analysis.

Results

We observed a significant (p < 0.0004) association of the CDH1 163+37235G>A variant (rs1125557) with DGC risk. Odds ratios were 4.55 (95%CI = 2.09–9.93) and 1.38 (95%CI = 0.75–2.55) for AA and GA carriers, respectively. When adjusted for age, sex, smoking status, alcohol intake and H. pylori infection, the risk estimates remained largely significant for AA carriers. Haplotype analysis suggested the 163+37235A-allele contributes to disease risk independently of the other variants studied.

Conclusion

The CDH1 163+37235G>A polymorphism may represent a novel susceptibility variant for sporadic DGC if confirmed in other populations. Considering the broad expression of E-cadherin in epithelia, this exploratory study encourages further evaluation of the 163+37235A-allele as a susceptibility variant in other carcinomas.
Literature
1.
Ushijima T, Sasako M: Focus on gastric cancer. Cancer Cell. 2004, 5: 121-125. 10.1016/S1535-6108(04)00033-9.CrossRefPubMed
2.
Lauren PA, Nevalainen TJ: Epidemiology of intestinal and diffuse types of gastric carcinoma. A time-trend study in Finland with comparison between studies from high- and low-risk areas. Cancer. 1993, 71: 2926-2933. 10.1002/1097-0142(19930515)71:10<2926::AID-CNCR2820711007>3.0.CO;2-X.CrossRefPubMed
3.
Humar B, Fukuzawa R, Blair V, Dunbier A, More H, Charlton A, Yang HK, Kim WH, Reeve AE, Martin I, Guilford P: Destabilized adhesion in the gastric proliferative zone and c-Src kinase activation mark the development of early diffuse gastric cancer. Cancer Res. 2007, 67: 2480-2489. 10.1158/0008-5472.CAN-06-3021.CrossRefPubMed
4.
Karayiannakis AJ, Syrigos KN, Chatzigianni E, Papanikolaou S, Karatzas G: E-cadherin expression as a differentiation marker in gastric cancer. Hepatogastroenterology. 1998, 45: 2437-2442.PubMed
5.
Larue L, Ohsugi M, Hirchenhain J, Kemler R: E-cadherin null mutant embryos fail to form a trophectoderm epithelium. Proc Natl Acad Sci USA. 1994, 91: 8263-8267. 10.1073/pnas.91.17.8263.CrossRefPubMedPubMedCentral
6.
Berx G, Becker KF, Hofler H, van Roy F: Mutations of the human E-cadherin (CDH1) gene. Hum Mut. 1998, 12: 226-237. 10.1002/(SICI)1098-1004(1998)12:4<226::AID-HUMU2>3.0.CO;2-D.CrossRefPubMed
7.
Tamura G, Yin J, Wang S, Fleisher AS, Zou T, Abraham JM, Kong D, Smolinski KN, Wilson KT, James SP, Silverberg SG, Nishizuka S, Terashima M, Motoyama T, Meltzer SJ: E-Cadherin gene promoter hypermethylation in primary human gastric carcinomas. J Natl Cancer Inst. 2000, 92: 569-573. 10.1093/jnci/92.7.569.CrossRefPubMed
8.
Guilford P, Hopkins J, Harraway J, McLeod M, McLeod N, Harawira P, Taite H, Scoular R, Miller A, Reeve AE: E-cadherin germline mutations in familial gastric cancer. Nature. 1998, 392: 402-405. 10.1038/32918.CrossRefPubMed
9.
10.
Humar B, Graziano F, Cascinu S, Catalano V, Ruzzo AM, Magnani M, Toro T, Burchill T, Futschik ME, Merriman T, Guilford P: Association of CDH1 haplotypes with susceptibility to sporadic diffuse gastric cancer. Oncogene. 2002, 21: 8192-8195. 10.1038/sj.onc.1205921.CrossRefPubMed
11.
Cattaneo F, Venesio T, Molatore S, Russo A, Fiocca R, Frattini M, Scovassi AI, Ottini L, Bertario L, Ranzani GN: Functional analysis and case-control study of -160C/A polymorphism in the E-cadherin gene promoter: association with cancer risk. Anticancer research. 2006, 26: 4627-4632.PubMed
12.
Medina-Franco H, Ramos-De la Medina A, Vizcaino G, Medina-Franco JL: Single nucleotide polymorphisms in the promoter region of the E-cadherin gene in gastric cancer: case-control study in a young Mexican population. Ann Surg Oncol. 2007, 14: 2246-2249. 10.1245/s10434-006-9054-4.CrossRefPubMed
13.
Yamada H, Shinmura K, Ikeda S, Tao H, Otani T, Hanaoka T, Tsuneyoshi T, Tsugane S, Sugimura H: Association between CDH1 haplotypes and gastric cancer risk in a Japanese population. Scand J Gastroenterol. 2007, 42: 1479-1485. 10.1080/00365520701478436.CrossRefPubMed
14.
Stemmler MP, Hecht A, Kemler R: E-cadherin intron 2 contains cis-regulatory elements essential for gene expression. Development. 2005, 132 (5): 965-976. 10.1242/dev.01662.CrossRefPubMed
15.
16.
17.
18.
Humar B, Toro T, Graziano F, Muller H, Dobbie Z, Kwang-Yang H, Eng C, Hampel H, Gilbert D, Winship I, Parry S, Ward R, Findlay M, Christian A, Tucker M, Tucker K, Merriman T, Guilford P: Novel germline CDH1 mutations in hereditary diffuse gastric cancer families. Hum Mut. 2002, 19: 518-525. 10.1002/humu.10067.CrossRefPubMed
19.
20.
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: 97-98. 10.1038/sj.cr.7290286.CrossRefPubMed
21.
22.
Driller K, Pagenstecher A, Uhl M, Omran H, Berlis A, Grunder A, Sippel AE: Nuclear factor I X deficiency causes brain malformation and severe skeletal defects. Mol Cell Biol. 2007, 27: 3855-3867. 10.1128/MCB.02293-06.CrossRefPubMedPubMedCentral
23.
Chaudhry AZ, Lyons GE, Gronostajski RM: Expression patterns of the four nuclear factor I genes during mouse embryogenesis indicate a potential role in development. Dev Dyn. 1997, 208: 313-325. 10.1002/(SICI)1097-0177(199703)208:3<313::AID-AJA3>3.0.CO;2-L.CrossRefPubMed
24.
Rafty LA, Santiago FS, Khachigian LM: NF1/X represses PDGF A-chain transcription by interacting with Sp1 and antagonizing Sp1 occupancy of the promoter. EMBO J. 2002, 21: 334-343. 10.1093/emboj/21.3.334.CrossRefPubMedPubMedCentral
25.
Ouellet S, Vigneault F, Lessard M, Leclerc S, Drouin R, Guerin SL: Transcriptional regulation of the cyclin-dependent kinase inhibitor 1A (p21) gene by NFI in proliferating human cells. Nucleic Acids Res. 2006, 34: 6472-6487. 10.1093/nar/gkl861.CrossRefPubMedPubMedCentral
26.
Luciakova K, Barath P, Poliakova D, Persson A, Nelson BD: Repression of the human adenine nucleotide translocase-2 gene in growth-arrested human diploid cells: the role of nuclear factor-1. J Biol Chem. 2003, 278: 30624-30633. 10.1074/jbc.M303530200.CrossRefPubMed
27.
Schuur ER, Kruse U, Iacovoni JS, Vogt PK: Nuclear factor I interferes with transformation induced by nuclear oncogenes. Cell Growth Differ. 1995, 6: 219-227.PubMed
28.
Furuya T, Uchiyama T, Adachi A, Chochi Y, Oga A, Kawauchi S, Ishiglo K, Sasaki K: Relation of DNA ploidy to genetic aberrations detected by chromosomal CGH and FISH in gastric adenocarcinomas. Oncol Rep. 2006, 15: 1491-1496.PubMed
29.
Weiss MM, Kuipers EJ, Postma C, Snijders AM, Pinkel D, Meuwissen SG, Albertson D, Meijer GA: Genomic alterations in primary gastric adenocarcinomas correlate with clinicopathological characteristics and survival. Cell Oncol. 2004, 26: 307-317.PubMedPubMedCentral
30.
Buffart TE, Carvalho B, Hopmans E, Brehm V, Kranenbarg EK, Schaaij-Visser TB, Eijk PP, van Grieken NC, Ylstra B, Velde van de CJ, Meijer GA: Gastric cancers in young and elderly patients show different genomic profiles. J Pathol. 2007, 211: 45-51. 10.1002/path.2085.CrossRefPubMed
31.
Pharoah PD, Oliveira C, Machado JC, Keller G, Vogelsang H, Laux H, Becker KF, Hahn H, Paproski SM, Brown LA, Caldas C, Huntsman D: CDH1 c-160a promotor polymorphism is not associated with risk of stomach cancer. Int J Cancer. 2002, 101: 196-197. 10.1002/ijc.10590.CrossRefPubMed
32.
33.
Wang GY, Lu CQ, Zhang RM, Hu XH, Luo ZW: The E-cadherin gene polymorphism 160C->A and cancer risk: A HuGE review and meta-analysis of 26 case-control studies. Am J Epidemiol. 2008, 167: 7-14. 10.1093/aje/kwm264.CrossRefPubMed
34.
Verhage BA, van Houwelingen K, Ruijter TE, Kiemeney LA, Schalken JA: Single-nucleotide polymorphism in the E-cadherin gene promoter modifies the risk of prostate cancer. Int J Cancer. 2002, 100: 683-685. 10.1002/ijc.10541.CrossRefPubMed
35.
Lindstrom S, Wiklund F, Jonsson BA, Adami HO, Balter K, Brookes AJ, Xu J, Zheng SL, Isaacs WB, Adolfsson J, Gronberg H: Comprehensive genetic evaluation of common E-cadherin sequence variants and prostate cancer risk: strong confirmation of functional promoter SNP. Hum Genet. 2005, 118: 339-347. 10.1007/s00439-005-0060-6.CrossRefPubMed
36.
Tsukino H, Kuroda Y, Nakao H, Imai H, Inatomi H, Kohshi K, Osada Y, Katoh T: E-cadherin gene polymorphism and risk of urothelial cancer. Cancer Lett. 2003, 195: 53-58. 10.1016/S0304-3835(03)00130-7.CrossRefPubMed
37.
Zhang X, Ma X, Zhu QG, Li LC, Chen Z, Ye ZQ: Association between a C/A single nucleotide polymorphism of the E-cadherin gene promoter and transitional cell carcinoma of the bladder. J Urol. 2003, 170: 1379-1382. 10.1097/01.ju.0000084297.43710.e9.CrossRefPubMed
38.
Yu JC, Hsu HM, Chen ST, Hsu GC, Huang CS, Hou MF, Fu YP, Cheng TC, Wu PE, Shen CY: Breast cancer risk associated with genotypic polymorphism of the genes involved in the estrogen-receptor-signaling pathway: a multigenic study on cancer susceptibility. J Biomed Sci. 2006, 13: 419-432. 10.1007/s11373-006-9069-7.CrossRefPubMed
39.
Shin Y, Kim IJ, Kang HC, Park JH, Park HW, Jang SG, Lee MR, Jeong SY, Chang HJ, Ku JL, Park JG: A functional polymorphism (-347 G-->GA) in the E-cadherin gene is associated with colorectal cancer. Carcinogenesis. 2004, 25: 2173-2176. 10.1093/carcin/bgh223.CrossRefPubMed
40.
41.
Cavallaro U, Christofori G: Cell adhesion and signalling by cadherins and Ig-CAMs in cancer. Nat Rev Cancer. 2004, 4 (2): 118-132. 10.1038/nrc1276.CrossRefPubMed
Metadata
Title
A novel diffuse gastric cancer susceptibility variant in E-cadherin (CDH1) intron 2: A case control study in an Italian population
Authors
Soroush Nasri
Helen More
Francesco Graziano
Annamaria Ruzzo
Emily Wilson
Anita Dunbier
Cushla McKinney
Tony Merriman
Parry Guilford
Mauro Magnani
Bostjan Humar
Publication date
01-12-2008
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2008
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-8-138

Other articles of this Issue 1/2008

BMC Cancer 1/2008 Go to the issue

Research article

Recurrent and multiple bladder tumors show conserved expression profiles

Research article

Depression and quality of life in cancer patients with and without pain: the role of pain beliefs

Research article

The reversal of recurrence hazard rate between ER positive and negative breast cancer patients with axillary lymph node dissection (pathological stage I-III) 3 years after surgery

Research article

Involvement of TSC genes and differential expression of other members of the mTOR signaling pathway in oral squamous cell carcinoma

Research article

Treatment delay of bone tumours, compilation of a sociodemographic risk profile: A retrospective study

Research article

Frequently increased epidermal growth factor receptor (EGFR) copy numbers and decreased BRCA1 mRNA expression in Japanese triple-negative breast cancers
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits