Abstract 2201: Long-term risk of colorectal cancer in patients with sessile serrated adenomas, traditional serrated adenomas, and hyperplastic polyps
Authors: Baron John A. , Erichsen Rune , Hamilton-Dutoit Stephen J. , Snover Dale C. , Torlakovic Emina E. , Frøslev Trine , Pedersen Lars , Vyberg Mogens , Hamilton Stanley R. , Sørensen Henrik T. 
Published: May 2015

Abstract
Evidence for the recently recognized serrated pathway to colorectal cancer (CRCa) is based largely on the similarity of genetic changes in CpG island methylator phenotype positive (CIMP+) cancers and serrated lesions such as the sessile serrated adenoma (SSA). There is limited evidence regarding the future cancer risks in patients diagnosed with these lesions.
Methods: We used Danish medical databases to select subjects for a population-based case-control study of CRCa within the population of 272,342 individuals who underwent colonoscopy during 1977 - 2009. 2,045 CRCa cases were diagnosed during 1977-2006. We used risk set sampling to select 8,105 controls matched by gender and year of birth to the cases. After accessing records of colorectal polyps identified in the subjects, we requested histopathological blocks for the first lesions diagnosed as hyperplastic polyps (HPs) at or after the first colonoscopy during the study period, and obtained them for 895 (97%) of the affected subjects. Four expert pathologists used current criteria to review these lesions and reclassify them as SSAs, traditional serrated adenomas (TSAs) or hyperplastic polyps (HPs). Lesions initially diagnosed as conventional adenomas (CADs) were not reviewed, nor were later polyps. We used conditional logistic regression to compute odds ratios (ORs) and 95% confidence limits (CIs) for CRCa associated with polyp types at the first examination recorded with HPs, using patients with no polyp history during the study period as the referent group and adjusting for age and year at first colonoscopy.
Results: After review, 48 (2.3%) cases and 81 (1.0%) controls had SSAs but no CADs or TSAs (OR for CRCa = 3.34, 95% CI: 2.31-4.83). TSAs conferred a similarly high CRCa risk (OR = 3.35, 95%CI: 1.39-8.07), but HPs did not (OR = 1.30, 95% CI: 0.96-1.77). The OR for CADs without SSA or TSA was 2.49 (95% CI: 2.23-2.79); subjects with both SSAs and CADs had an OR intermediate between those for CADs alone and SSAs alone. Women with SSAs and no CADs had a higher OR (4.92; 95% CI: 2.96-8.18) than men (OR = 2.18, 95% CI: 1.24-3.82). Proximal SSAs were associated with a particularly high OR (12.39, 95% CI: 4.87-31.51). Consideration of reported metachronous lesions changed most of these ORs only modestly.
Conclusions: We found that SSAs and TSAs are associated with a substantial increase in the risk of CRCa. These data provide further evidence for the serrated pathway to CRCa, with SSAs and TSAs as cancer precursors.
Citation Format: John A. Baron, Rune Erichsen, Stephen J. Hamilton-Dutoit, Dale C. Snover, Emina E. Torlakovic, Trine Frøslev, Lars Pedersen, Mogens Vyberg, Stanley R. Hamilton, Henrik T. Sørensen. Long-term risk of colorectal cancer in patients with sessile serrated adenomas, traditional serrated adenomas, and hyperplastic polyps. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2201. doi:10.1158/1538-7445.AM2014-2201