RISK OF ADVANCED NEOPLASIA AND NUMBER OF FAMILY MEMBERS WITH MICROSATELLITE STABLE COLORECTAL CANCER

Abstract

<p><strong>Introduction: </strong>Although family history of colorectal cancer (CRC) is a known risk factor of CRC, no study thus far stratify the risk according to microsatellite instability (MSI) status. In particular, the role of screening first degree relatives (FDR) with microsatellite stable (MSS) CRC remains unknown. We characterize the risk of advanced neoplasia in individuals with family history of young onset MSS-CRC.<br><strong>Methods: </strong>We have enrolled a prospective cohort of FDR of patients with MSS-CRC with onset age <60 years. All FDR underwent screening colonoscopy for colorectal neoplasm. Baseline demographic, detailed family history, presence of comorbidity and concurrent medications were collected. Primary outcome was detection of advanced neoplasia including advanced adenoma (defined as an adenoma ≧10mm or ≧25%villous histology or high -grade dysplasia) and cancer. Multiple logistic regression was used to calculate the adjusted odd ratio (OR).<br><strong>Result: </strong>A total of 407 subjects (mean age 48.3 [SD 14.3] years with 230 [56.5%] male) from 216 CRC families were analysed. Among them, 97 (23.8%) had ≧2 FDR with CRC and 364 (89.4%) had at least one FDR diagnosed with CRC <50 years. The overall adenoma detection rate was 34.4% (n=140) and advanced adenoma detection rate was 8.8% (n =36). Three subjects (0.7%) were diagnosed to have CRC at age of 44 to 61, and all of them had ≧2 FDR with CRC. Older age (≧50 years) (adjusted OR: 4.73, 95%CI:2.01-11.1, p <0.001), regular drinker (adjusted OR: 3.26, 95%CI: 1.08-9.85m p =0.036) and ≧2 FDR with CRC (adjusted OR: 2.23, 95%CI: 1.09-4.54, p=0.027) were significant risk factors for advanced neoplasia. There was a strong correlation between the number of FDR with CRC in the family and detection of CRC (Pearson correlation: 0.99, p = 0.001; Figure 1). When compared to individuals with only one FDR with CRC in the family, there were significantly higher rates of polyp, adenoma, advanced adenoma and cancer among those with ≧2 FDR.<br><strong>Conclusion: </strong>The current study found that among those with family history of MSS-CRC, individuals with ≧2 FDR with CRC was a significant risk factor for both CRC and advanced adenoma.</p>