Post-colonoscopy colorectal cancer: the key role of molecular pathological epidemiology.

Transl Gastroenterol Hepatol 2017;2:9 tgh.amegroups.com Post-colonoscopy colorecta l cancer or so-cal led “interval cancer” has emerged as one of new research topics, attracting much attention of endoscopists, gastroenterologists, and oncologists alike (1-4). In addition to lesions missed during the index colonoscopy due to technical issues (e.g., skills of endoscopists, quality of bowel preparation) or tumor morphology (e.g., sessile serrated adenoma/polyps) (5), some tumors arising after colonoscopy may have rapidly-growing biological behavior with distinct molecular and pathological features (1-4). Colonoscopy has remained the cornerstone of colorectal cancer screening which can provide primary prevention, early detection, and pathological diagnosis of neoplastic lesions, potentially leading to the reduction in colorectal cancer incidence and mortality (4,6). In the U.S., screening colonoscopy has been increasingly utilized since Medicare, a national social insurance program, initiated coverage of this procedure in 2001 (6). The U.S. Preventive Services Task Force (USPSTF) statement in 2016 recommends screening of the colon and rectum for average-risk asymptomatic individuals aged 50–75 years, and refers to positive family history, male sex, and black race as risk factors for colorectal cancer (7). Follow-up colonoscopy after negative findings or polypectomy is scheduled according to the number, size, and/or pathological findings of polyps on the index colonoscopy (8). However, a fraction of people develop colorectal cancer between the index and subsequent surveillance procedures. In a meta-analysis of 12 observational studies, the pooled prevalence of interval cancer was 3.7% [95% confidence interval (CI), 2.8–4.9%] among all colorectal cancer cases (1). This analysis also suggests that interval cancer is more likely to be located in the proximal colon, and old age and positive family history of colorectal cancer are potential risk factors (1). Accumulating evidence indicates specific molecular and pathological features associated with post-colonoscopy colorectal cancer. Our previous study based on two U.S. prospective cohort studies has shown not only the effectiveness of colonoscopy on risk reduction of colorectal cancer incidence and mortality but also distinct molecular alterations in post-colonoscopy tumors (4). Among 1,815 incident colorectal cancer patients during the study period of more than 22 years for 88,902 participants, we examined tumor molecular features of 62 patients diagnosed within 5 years after the index colonoscopy. Compared with tumors diagnosed more than 5 years after colonoscopy or without any prior colonoscopy, post-colonoscopy tumors were more likely to show high-degree microsatellite instability [MSIhigh; odds ratio (OR), 2.10; 95% CI, 1.10–4.02], highdegree CpG island methylator phenotype (CIMP-high; OR, Editorial