Abstract 5490: Prospective study of seroreactivity to JC virus T-Antigen and risk of colorectal cancers and adenomas

Abstract

Abstract JC virus (JCV) has been hypothesized to play a role in the development of colorectal cancer (CRC), although findings are inconsistent across studies. Case series have reported the presence of JCV DNA in tumors, but two serological studies observed no statistically significant association between circulating antibodies to JCV capsid protein and risk of CRC. No epidemiologic study has examined the association between antibodies to the JCV oncoprotein, T-antigen, and cancer. To investigate the association between circulating levels of JCV T-Ag antibodies and the risk of CRC and adenomas, we conducted a case-control study nested within a community-based cohort established in Washington County, MD, in 1989. Cancer registries were used to identify incident cases of CRC occurring within this cohort through 2006 (n=251), and 123 colonoscopy-detected adenoma cases were initially self-reported through a follow-up questionnaire and subsequently verified through pathology report review. Controls were selected from cohort participants who did not develop CRC or adenomas and matched to cases on age, sex, race, date of blood draw, and for adenoma cases, date of endoscopy. Recombinant protein-based enzyme linked immunosorbent assays (ELISA) were used to measure JCV T-Ag antibodies in baseline pre-diagnostic plasma samples. High versus low seroreactivity was defined using the median value among the controls. Conditional logistic regression was used to calculate odds ratios (OR's) and 95% confidence intervals (CI). Overall, high JCV T-Ag seroreactivity was not associated with development of CRC (OR=1.24, 95% CI=0.84-1.84) or adenoma (OR=1.18, 95% CI=0.67-2.09). Among females, high JCV T-Ag seroreactivity was associated with an increased risk of CRC (OR=1.78, 95% CI=1.00-3.17), whereas no association was observed among males (OR=0.89, 95% CI=0.51-1.54). High JCV T-Ag seroreactivity was associated with non-statistically significant risks of rectal cancer (OR=1.55, 95% CI=0.72-3.30) and CRC diagnosed at distant stage (OR=2.25, 95% CI=0.69-7.31), but not with distal or proximal colon cancer or CRC diagnosed at local/regional stages. High JCV T-Ag seroreactivity was not associated with increased risk of adenomas overall or by gender. However, a statistically significant association was observed between high JCV T-Ag seroreactivity and adenomas of the proximal colon (OR=2.80, 95% CI=1.01-7.77), but not the distal colon. No clear differences in risk were observed when results were stratified by adenoma size or histology. These results suggest that associations between JCV infection and CRC/adenomas may differ by gender and anatomic site. Further studies incorporating multiple serologic and DNA-based markers are needed to better understand the relationship between JCV infection and CRC/adenomas. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5490. doi:1538-7445.AM2012-5490