title: Ulcerative colitis neoplasia is not associated with common inflammatory bowel disease single-nucleotide polymorphisms.
abstract: BACKGROUND
  Neoplasia complicating ulcerative colitis (UC-neoplasia) is a problem that is poorly addressed by present surveillance techniques. The association of greater than 300 single nucleotide polymorphisms (SNPs) with inflammatory bowel disease (IBD) suggests the possibility that certain genetic polymorphisms might identify patients with UC destined for malignant degeneration. This present study tested the hypothesis that presently known IBD-associated SNPs may correlate with UC-neoplasia.
  
  
  METHODS
  A total of 41 patients with UC-neoplasia (mean age 56 ± 2.1 years) were identified from our divisional IBD Biobank (low-grade dysplasia n = 13, high-grade dysplasia n = 8, colorectal cancer [CRC] n = 20). These patients were individually age, sex, and disease duration matched with UC patients without neoplasia. Primary sclerosing cholangitis and family history of CRC were recorded. Patients were genotyped for 314 of the most commonly IBD-associated SNPs by a custom SNP microarray. Logistic regression and Fischer exact test were used for statistical analysis.
  
  
  RESULTS
  After Bonferroni correction, none of the 314 IBD-associated SNPs correlated with UC-neoplasia when compared with matched UC controls. The incidence of primary sclerosing cholangitis was greater in the UC-neoplasia group (10/41, 24% vs 3/41, 7%; P = .03) compared with UC controls. The severity of neoplasia (low grade dysplasia versus high grade dysplasia versus CRC) correlated with disease duration (7.9 vs 13.4 vs 20.7 years, respectively).
  
  
  CONCLUSIONS
  The lack of correlation between well-known IBD-associated SNPs and UC-neoplasia demonstrated in this study suggests that the development of neoplasia in patients with UC is associated with genetic determinants other than those that predispose to inflammation or results from posttranslational modifications or epigenetic factors rather than germline polymorphisms.
authors.affiliation: Division of Colon and Rectal Surgery, College of Medicine, The Pennsylvania State University, Hershey, PA.
authors.forename: Tara M
authors.initials: TM
authors.lastname: Connelly
authors.affiliation: Department of Biostatistics, College of Medicine, The Pennsylvania State University, Hershey, PA.
authors.forename: Arthur S
authors.initials: AS
authors.lastname: Berg
authors.affiliation: Division of Colon and Rectal Surgery, College of Medicine, The Pennsylvania State University, Hershey, PA.
authors.forename: Leonard R
authors.initials: LR
authors.lastname: Harris
authors.affiliation: Division of Colon and Rectal Surgery, College of Medicine, The Pennsylvania State University, Hershey, PA.
authors.forename: David L
authors.initials: DL
authors.lastname: Brinton
authors.affiliation: Division of Colon and Rectal Surgery, College of Medicine, The Pennsylvania State University, Hershey, PA.
authors.forename: John P
authors.initials: JP
authors.lastname: Hegarty
authors.affiliation: Division of Colon and Rectal Surgery, College of Medicine, The Pennsylvania State University, Hershey, PA.
authors.forename: Sue M
authors.initials: SM
authors.lastname: Deiling
authors.affiliation: Division of Colon and Rectal Surgery, College of Medicine, The Pennsylvania State University, Hershey, PA.
authors.forename: David B
authors.initials: DB
authors.lastname: Stewart
authors.affiliation: Division of Colon and Rectal Surgery, College of Medicine, The Pennsylvania State University, Hershey, PA. Electronic address: wkoltun@psu.edu.
authors.forename: Walter A
authors.initials: WA
authors.lastname: Koltun
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015209:Cholangitis, Sclerosing / Q000150:complications / Q000235:genetics; D015331:Cohort Studies; D003093:Colitis, Ulcerative / Q000150:complications* / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000209:etiology* / Q000235:genetics* / Q000473:pathology; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000150:complications / Q000235:genetics; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult