Ulcerative colitis neoplasia is not associated with common inflammatory bowel disease single-nucleotide polymorphisms Tara M. Connelly, MB, BCh, MSc, a Arthur S. Berg, PhD, b Leonard R. Harris III, BS, a David L. Brinton, CRNP, a John P. Hegarty, PhD, a Sue M. Deiling, BA, a David B. Stewart, MD, FACS, FASCRS, a and Walter A. Koltun, MD, FACS, FASCRS, a Hershey, PA 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. Materials and 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). Conclusion. 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 post- translational modifications or epigenetic factors rather than germline polymorphisms. (Surgery 2014;156:253-62.) From the Division of Colon and Rectal Surgery a and Department of Biostatistics, b College of Medicine, The Pennsylvania State University, Hershey, PA PATIENTS WITH ULCERATIVE COLITIS (UC) have increased rates of colorectal carcinoma (CRC) compared to the general population, with risk most closely correlating with disease extent and duration. 1-6 The current inflammatory bowel disease (IBD)- CRC model involves the progression of healthy tis- sue from inflamed to low-grade dysplasia (LGD) to high-grade dysplasia (HGD) to carcinoma. 7 How- ever, importantly, this model can only be thought of as a very rough guide because progression from normal mucosa to cancer is not always observed in the previously stated order. Patients with UC not uncommonly have HGD or CRC discovered without previous evidence of LGD and often UC-CRC develops at an accelerated pace compared with sporadic CRC. UC-CRC risk increases markedly with duration of UC with a cumulative CRC probability of 2% within 10 years, 8% by 20 years, and 18% by 30 years. 8 Additionally, patients with a concomitant The Division of Colon and Rectal Surgery is the recipient of the Carlino Fund for IBD research. All authors have no other dis- claimers or financial conflicts of interest. Presented at the 9th Annual Academic Surgical Congress in San Diego, CA, February 4À6, 2014. Accepted for publication March 7, 2014. Reprint requests: Walter A. Koltun, MD, FACS, FASCRS, Chief, Division of Colon and Rectal Surgery, Department of Surgery, The Pennsylvania State University, College of Medicine, 500 University Drive, H137, P. O. Box 850, Hershey, PA 17033- 0850. E-mail: wkoltun@psu.edu. 0039-6060/$ - see front matter Ó 2014 Mosby, Inc. All rights reserved. http://dx.doi.org/10.1016/j.surg.2014.03.017 SURGERY 253