352 Elevated Risk of Advanced Adenomas and Colorectal Cancer in Relatives of Patients With Advanced Adenomas: A Population-Based Study in Utah

Abstract

INTRODUCTION: Colorectal cancer (CRC) is the third most common cancer in the USA. Prior studies have established that the risk of CRC is increased in first-degree relatives (FDR) of patients with CRC. Current guidelines recommend individuals with a FDR diagnosed with CRC or advanced adenoma (AA) before age 60 should undergo screening colonoscopy starting at age 40. Many of these studies rely on patient recall regarding family history and therefore lack verification of reported diagnoses. In this retrospective, population-based, case-control study we quantified the prevalence of AA and CRC in the relatives (FDR, second degree-SDR or third degree-TDR) of patients with an AA. Our study is the first population based assessment of the risk of CRC and AA in FDR, SDR or TDR of individuals with an AA. This study will provide evidence for or against the current screening guidelines. METHODS: We performed a population-based retrospective case-control study of residents of the state of Utah, between 50 and 80 years of age, who underwent colonoscopy between February 15, 1995 and January 31, 2009 at Intermountain Healthcare or University of Utah Health System. De-identified medical information on patients undergoing colonoscopy was merged with cancer histories from the Utah Cancer Registry and overlaid on pedigrees from the Utah Population Database to investigate the familial aggregation of AA andCRC. Advanced adenomas were defined, for query purposes, as cases with villous histology, a snare procedure was used or the words “multiple” or “many” were used in the colonoscopy report. Cox regression analysis was used to assess the relative risk of AA and CRC development in relatives. RESULTS: There were 126,936 unique patients who underwent colonoscopy. 22,364 patients had an AA removed at colonoscopy and they defined the case population. For each case, 1 randomly selected, ageand sex-matched control was selected from the population who had AA-free colonoscopy. The prevalence of an AA was increased in FDRs (OR 1.31, 95% CI, 1.18-1.45), SDRs (OR 1.21, 95% CI, 1.1-1.33) and TDRs (OR 1.07, 95% CI, 1.01-1.13) of cases compared to controls. An elevated risk of CRC was found in probands (OR 7.64, 95% CI, 6.14-9.51) and in FDRs (RR 1.7, 95% CI: 1.46-1.98) compared to controls. However, more distant relatives (SDR/TDR) did not have a statistically elevated risk of CRC. DISCUSSION: In this study we report that FDRs, SDRs and TDRs of individuals with AA had an increased risk of developing AA themselves. The strength of the association showed a relationship based on the degree of kinship. Similarly, the risk of colorectal cancer was increased in the cases as well as in their FDRs. Our data supports the current CRC screening guidelines and raises the question of whether such screening should be extended to more distant members of the patient's family.