Risk Factors for Early-Onset Colorectal Cancer Study GroupResults Clini al FindingVeterans 18 -49 years of age undergoing colonoscopy loss may be an early clinical sign of early-onset colorectal cancer

ObjectiveTo conduct an anatomic site-specific case–control study of candidate colorectal cancer (CRC) risk factors.DesignCase–control study of US veterans with >1 colonoscopy during 1999–2011. Cases had cancer registry-identified CRC at colonoscopy, while controls were CRC free at colonoscopy and within 3 years of colonoscopy. Primary outcome was CRC, stratified by anatomic site: proximal, distal, or rectal. Candidate risk factors included age, sex, race/ethnicity, body mass index, height, diabetes, smoking status, and aspirin exposure summarised by adjusted ORs and 95% CIs.Results21 744 CRC cases (n=7017 rectal; n=7039 distal; n=7688 proximal) and 612 646 controls were included. Males had significantly higher odds relative to females for rectal cancer (OR=2.84, 95% CI 2.25 to 3.58) than distal cancer (OR=1.84, 95% CI 1.50 to 2.24). Relative to whites, blacks had significantly lower rectal cancer odds (OR=0.88, 95% CI 0.82 to 0.95), but increased distal (OR=1.27, 95% CI 1.19 to 1.37) and proximal odds (OR=1.62, 95% CI 1.52 to 1.72). Diabetes prevalence was more strongly associated with proximal (OR=1.29, 95% CI 1.22 to 1.36) than distal (OR=1.15, 95% CI 1.08 to 1.22) or rectal cancer (OR=1.12, 95% CI 1.06 to 1.19). Current smoking was more strongly associated with rectal cancer (OR=1.81, 95% CI 1.68 to 1.95) than proximal cancer (OR=1.53, 95% CI 1.43 to 1.65) or distal cancer (OR=1.46, 95% CI 1.35 to 1.57) compared with never smoking. Aspirin use was significantly more strongly associated with reduced rectal cancer odds (OR=0.71, 95% CI 0.67 to 0.76) than distal (OR=0.85, 95% CI 0.81 to 0.90) or proximal (OR=0.91, 95% CI 0.86 to 0.95).ConclusionCandidate CRC risk factor associations vary significantly by anatomic site. Accounting for site may enable better insights into CRC pathogenesis and cancer control strategies.

In a retrospective study of patients at a Veterans' administration healthcare system, replacing the gFOBT with the FIT increased the proportion of patients who completed CRC screening. Replacement of the gFOBT with the FIT should be strongly considered by all healthcare systems.

BACKGROUND AND AIMS: Incidence and mortality from early onset colorectal cancer (CRC) is rising. Adenoma detection, removal and subsequent endoscopic surveillance may modify risk of CRC diagnosed prior to age 50 (early onset CRC). We conducted a systematic review of young onset adenoma (YOA) prevalence, associated risk factors, and rate of metachronous advanced neoplasia after YOA diagnosis. METHODS:Through a systematic search of multiple electronic databases through 2/12/2019, we identified studies with individuals age 18 to 49 years which reported on prevalence of adenoma, risk factors for adenoma, and/or risk for metachronous advanced neoplasia. Summary estimates were derived using random effects meta-analysis, when feasible. RESULTS:Pooled overall prevalence of YOA was 9.0% (95% CI: 7.1%-11.4%) based on 24 studies including 23,142 individuals. On subgroup analysis, pooled prevalence of YOA for autopsy studies was 3.9% (95% CI: 1.9%-7.6%), while prevalence for colonoscopy studies was 10.7% (95% CI: 8.5%-13.5). Only advancing age was identified as a consistent risk factor for YOA based on 4 studies including 78,880 individuals. Pooled rate of metachronous advanced neoplasia after baseline YOA diagnosis was 6.0% (95% CI: 4.1%-8.6%), based on 3 studies including 1,493 individuals undergoing follow-up colonoscopy, with only 1 CRC case reported.Overall there were very few studies reporting metachronous advanced neoplasia, and no studies evaluating whether routine surveillance colonoscopy decreases risk of CRC. CONCLUSIONS:Prevalence of YOA is estimated to be 9% and increases with age. Risk for metachronous advanced neoplasia after YOA diagnosis is estimated to be 6%. More research is needed to understand the prevalence, risk factors, and risk of CRC associated with YOA.

Purpose Cancer ascertainment using large-scale electronic health records is a challenge. Our aim was to propose and apply a structured approach for evaluating multiple candidate approaches for cancer ascertainment using colorectal cancer (CRC) ascertainment within the US Department of Veterans Affairs (VA) as a use case. Methods The proposed approach for evaluating cancer ascertainment strategies includes assessment of individual strategy performance, comparison of agreement across strategies, and review of discordant diagnoses. We applied this approach to compare three strategies for CRC ascertainment within the VA: administrative claims data consisting of International Classification of Diseases, Ninth Revision (ICD9) diagnosis codes; the VA Central Cancer Registry (VACCR); and the newly accessible Oncology Domain, consisting of cases abstracted by local cancer registrars. The study sample consisted of 1,839,043 veterans with index colonoscopy performed from 1999 to 2014. Strategy-specific performance was estimated based on manual record review of 100 candidate CRC cases and 100 colonoscopy controls. Strategies were further compared using Cohen’s κ and focused review of discordant CRC diagnoses. Results A total of 92,197 individuals met at least one CRC definition. All three strategies had high sensitivity and specificity for incident CRC. However, the ICD9-based strategy demonstrated poor positive predictive value (58%). VACCR and Oncology Domain had almost perfect agreement with each other (κ, 0.87) but only moderate agreement with ICD9-based diagnoses (κ, 0.51 and 0.57, respectively). Among discordant cases reviewed, 15% of ICD9-positive but VACCR- or Oncology Domain–negative cases had incident CRC. Conclusion Evaluating novel strategies for identifying cancer requires a structured approach, including validation against manual record review, agreement among candidate strategies, and focused review of discordant findings. Without careful assessment of ascertainment methods, analyses may be subject to bias and limited in clinical impact.