title: Potentially functional polymorphisms in the CASP7 gene contribute to gastric adenocarcinoma susceptibility in an eastern Chinese population.
abstract: BACKGROUND
  Caspase 7 (CASP7) is an important regulator and executioner in the apoptosis pathway and plays a crucial role in cancer development and progression. However, few studies have evaluated associations between functional single nucleotide polymorphisms (SNPs) in the 3' untranslational region (UTR) of CASP7 and risk of gastric cancer.
  
  
  METHODS
  In a case-control study of 1117 patients with gastric cancer and 1146 cancer-free controls with frequency matching on age and sex, we genotyped four potentially functional SNPs (rs4353229T>C, rs10787498T>G, rs1127687G>A and rs12247479G>A) located in the microRNA binding sites of the CASP7 3' UTR by using Taqman assays and evaluated their associations with risk of gastric cancer by using logistic regression analyses as well as multifactorial dimension reduction (MDR) analysis.
  
  
  RESULTS
  In the single-locus analysis, only the CASP7 rs4353229 TT genotype was associated with 0.83-fold decreased risk (95% confidence interval [CI] = 0.70-0.98) of gastric cancer under a recessive model, compared with the CT/CC genotypes. In the combined analysis of all four SNPs, we found that the risk of gastric cancer decreased by 19% in those carrying any of the risk genotypes (adjusted odds ratio = 0.81, 95% CI = 0.68-0.96), compared with those carrying zero risk genotypes, and this risk was more evident in subgroups of younger age (<59 years), females, non-smokers, non-drinkers and patients with non-gastric cardia adenocarcinoma. Further MDR analysis suggested some evidence of interactions between the combined genotypes and other risk factors for gastric cancer.
  
  
  CONCLUSIONS
  Potentially functional CASP7 variants may contribute to risk of gastric cancer. Larger studies with different ethnic populations are warranted to validate our findings.
authors.affiliation: Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China ; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Meng-Yun
authors.initials: MY
authors.lastname: Wang
authors.forename: Mei-Ling
authors.initials: ML
authors.lastname: Zhu
authors.forename: Jing
authors.initials: J
authors.lastname: He
authors.forename: Ting-Yan
authors.initials: TY
authors.lastname: Shi
authors.forename: Qiao-Xin
authors.initials: QX
authors.lastname: Li
authors.forename: Ya-Nong
authors.initials: YN
authors.lastname: Wang
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Zhou
authors.forename: Meng-Hong
authors.initials: MH
authors.lastname: Sun
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Wang
authors.forename: Ya-Jun
authors.initials: YJ
authors.lastname: Yang
authors.forename: Jiu-Cun
authors.initials: JC
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Jin
authors.forename: Qing-Yi
authors.initials: QY
authors.lastname: Wei
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D053179:Caspase 7 / Q000235:genetics*; D002461:Cell Line, Transformed; D002681:China; D005260:Female; D005787:Gene Frequency; D023061:Gene Order; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics*; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; D053179:Caspase 7
references.citation: Hum Immunol. 2012 Jul;73(7):736-9
references.pmid: 22548721
references.citation: J Natl Cancer Inst. 2004 Mar 17;96(6):434-42
references.pmid: 15026468
references.citation: Ann N Y Acad Sci. 2003 Nov;1005:340-3
references.pmid: 14679087
references.citation: Carcinogenesis. 2013 Apr;34(4):936-42
references.pmid: 23275154
references.citation: Trends Genet. 2010 Mar;26(3):132-41
references.pmid: 20106545
references.citation: Carcinogenesis. 2011 Mar;32(3):336-42
references.pmid: 21148629
references.citation: Rheumatology (Oxford). 2007 Aug;46(8):1243-7
references.pmid: 17504820
references.citation: Aging (Albany NY). 2012 May;4(5):330-49
references.pmid: 22683550
references.citation: Carcinogenesis. 2010 Jul;31(7):1259-63
references.pmid: 20453000
references.citation: J Gastroenterol. 2000;35 Suppl 12:84-9
references.pmid: 10779225
references.citation: Cancer Res. 2008 Oct 15;68(20):8535-40
references.pmid: 18922928
references.citation: PLoS One. 2012;7(3):e31932
references.pmid: 22412849
references.citation: Lung Cancer. 2009 Jul;65(1):19-24
references.pmid: 19058873
references.citation: Gastrointest Cancer Res. 2007 Jan;1(1):12-9
references.pmid: 19262698
references.citation: Am J Hum Genet. 2001 Jul;69(1):138-47
references.pmid: 11404819
references.citation: Oncogene. 2003 Nov 24;22(53):8543-67
references.pmid: 14634618
references.citation: Hum Pathol. 2001 May;32(5):461-7
references.pmid: 11381362
references.citation: Blood. 2009 Mar 19;113(12):2742-5
references.pmid: 19168786
references.citation: Nucleic Acids Res. 2007;35(13):4535-41
references.pmid: 17584784
references.citation: Nat Rev Cancer. 2006 Apr;6(4):259-69
references.pmid: 16557279
references.citation: CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90
references.pmid: 21296855
references.citation: Nat Genet. 2007 Oct;39(10):1278-84
references.pmid: 17893677
references.citation: APMIS. 2004 Jun;112(6):330-5
references.pmid: 15511269
references.citation: Carcinogenesis. 2011 Nov;32(11):1668-74
references.pmid: 21934093
references.citation: Hum Genet. 2012 Jul;131(7):1235-44
references.pmid: 22371296
references.citation: Oncogene. 2003 Sep 11;22(39):8048-52
references.pmid: 12970753
references.citation: J Clin Oncol. 2006 May 10;24(14):2137-50
references.pmid: 16682732
references.citation: Cancer Causes Control. 2008 Sep;19(7):689-701
references.pmid: 18293090
references.citation: Science. 2006 Feb 10;311(5762):847-51
references.pmid: 16469926
references.citation: Cell Death Dis. 2011 Sep 01;2:e205
references.pmid: 21881607
references.citation: Cancer Epidemiol Biomarkers Prev. 2009 Jul;18(7):2114-22
references.pmid: 19531679
references.citation: Science. 1995 Mar 10;267(5203):1456-62
references.pmid: 7878464
references.citation: Cell. 2004 Jan 23;116(2):205-19
references.pmid: 14744432
references.citation: Nat Rev Cancer. 2010 Jun;10(6):389-402
references.pmid: 20495573
references.citation: Nat Genet. 2010 Sep;42(9):764-7
references.pmid: 20729852
references.citation: BMC Bioinformatics. 2010 Dec 17;11:600
references.pmid: 21167019
references.citation: Cell. 2004 Jan 23;116(2):281-97
references.pmid: 14744438