Abstract
BackgroundFirst-degree relatives (FDR) of patients with colorectal cancer have a higher risk of developing colorectal cancer than the general population. For this reason, screening guidelines recommend colonoscopy every 5 or 10 y, starting at the age of 40, depending on whether colorectal cancer in the index-case is diagnosed at <60 or ≥60 y, respectively. However, studies on the risk of neoplastic lesions are inconclusive. The aim of this study was to determine the risk of advanced neoplasia (three or more non-advanced adenomas, advanced adenoma, or invasive cancer) in FDR of patients with colorectal cancer compared to average-risk individuals (i.e., asymptomatic adults 50 to 69 y of age with no family history of colorectal cancer).Methods and FindingsThis cross-sectional analysis includes data from 8,498 individuals undergoing their first lifetime screening colonoscopy between 2006 and 2012 at six Spanish tertiary hospitals. Of these individuals, 3,015 were defined as asymptomatic FDR of patients with colorectal cancer (“familial-risk group”) and 3,038 as asymptomatic with average-risk for colorectal cancer (“average-risk group”). The familial-risk group was stratified as one FDR, with one family member diagnosed with colorectal cancer at ≥60 y (n = 1,884) or at <60 y (n = 831), and as two FDR, with two family members diagnosed with colorectal cancer at any age (n = 300). Multiple logistic regression analysis was used for between-group comparisons after adjusting for potential confounders (age, gender, and center). Compared with the average-risk group, advanced neoplasia was significantly more prevalent in individuals having two FDR with colorectal cancer (odds ratio [OR] 1.90; 95% confidence interval [CI] 1.36–2.66, p < 0.001), but not in those having one FDR with colorectal cancer diagnosed at ≥60 y (OR 1.03; 95% CI 0.83–1.27, p = 0.77) and <60 y (OR 1.19; 95% CI 0.90–1.58, p = 0.20). After the age of 50 y, men developed advanced neoplasia over two times more frequently than women and advanced neoplasia appeared at least ten y earlier. Fewer colonoscopies by 2-fold were required to detect one advanced neoplasia in men than in women.Major limitations of this study were first that although average-risk individuals were consecutively included in a randomized control trial, this was not the case for all individuals in the familial-risk cohort; and second, the difference in age between the average-risk and familial-risk cohorts.ConclusionsIndividuals having two FDR with colorectal cancer showed an increased risk of advanced neoplasia compared to those with average-risk for colorectal cancer. Men had over 2-fold higher risk of advanced neoplasia than women, independent of family history. These data suggest that screening colonoscopy guidelines should be revised in the familial-risk population.
Highlights
Clinical guidelines recommend more intensive surveillance in first-degree relatives (FDR) of patients with colorectal cancer than in average-risk individuals, as their risk of developing colorectal cancer is 2- to 4-fold higher [1,2,3,4]
Men had over 2-fold higher risk of advanced neoplasia than women, independent of family history
The current study was planned in March 2011 as a post-hoc analysis of three prospective studies [18,19,20]: one study that assessed the perfomance of fecal immunochemical testing in asymptomatic First-degree relatives (FDR) of patients with colorectal cancer [18], one randomized control trial (RCT) that assessed the efficacy of fecal immunochemical testing and colonoscopy as screening methods in asymptomatic FDR of patients with colorectal cancer [19], and one RCT that assessed the efficacy of fecal immunochemical testing and colonoscopy as screening methods in asymptomatic average-risk individuals [20]
Summary
Clinical guidelines recommend more intensive surveillance in first-degree relatives (FDR) of patients with colorectal cancer than in average-risk individuals, as their risk of developing colorectal cancer is 2- to 4-fold higher [1,2,3,4]. Colonoscopy every 5 [3,6,7,8] or 10 [3] y, depending on the number of relatives affected and age at cancer diagnosis, is the predominant screening strategy for these individuals, as it is the most effective procedure to detect and remove advanced adenomas This recommendation is not supported by prospective studies. There are no large-scale studies comparing the prevalence of advanced adenomas in asymptomatic familial- and average-risk individuals stratified by number of affected relatives, age and gender. Clarification on this issue in different familial-risk groups is crucial to guide future screening recommendations for this population. Many countries run screening programs to detect the earliest signs of colorectal cancer in apparently healthy people
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