Genomics of Hereditary Colorectal Cancer: Lessons Learnt from 25 Years of the Singapore Polyposis Registry

<p><b>INTRODUCTION</b>The Singapore Polyposis Registry (SPR) was established in 1989 in Singapore General Hospital (SGH). The aims were to provide a central registry service to facilitate identification, surveillance and management of families and individuals at high risk of colorectal cancer.</p><p><b>MATERIALS AND METHODS</b>This is a review of published literature in the department.</p><p><b>RESULTS</b>The registry currently has 253 families with several genetic conditions-93 familial adenomatous polyposis (FAP) families, 138 Amsterdam-criteria positive presumed Lynch syndrome (LS) families, 12 families with Peutz Jeghers syndrome, 2 families with Cowden's syndrome, and 8 families with hereditary mixed polyposis syndrome (HMPS). There are also 169 families with a strong family history of colorectal cancer but no abnormal genes yet identified. In FAP, a diagnostic tool developed has allowed a 94% local APC germline detection rate in FAP families. Knowledge obtained studying the phenotype of FAP patients has allowed better choice of surgery between ileal pouch anal anastomosis (IPAA) against an ileal-rectal anastomosis (IRA). In LS, our review has noted a highly heterogenous mutational spectrum and novel variants made up 46.7% (28/60) of all variants identified in this cohort. This may suggest that our Southeast Asian ethnic groups have distinct mutational variants from Western populations. Pathogenic mutations were only confined to MLH1 and MSH2, and identified in 28.8% of families.</p><p><b>CONCLUSION</b>The impact of predictive gene testing for hereditary cancer risk in clinical practice has allowed evolution of care. Risk-reducing surgery and aggressive surveillance allows reduction in morbidity and mortality of patients. The SPR will continue to grow and improve outcomes in hereditary colorectal cancer patients and families.</p>

Opportunistic screening for colorectal neoplasia in Singapore using faecal immunochemical occult blood test

<p><b>INTRODUCTION</b>The use of faecal immunochemical occult blood test (FIT) has been reported to decrease mortality from colorectal cancer. The Singapore Cancer Society (SCS) gives out FIT kits to encourage opportunistic screening of colorectal cancer. Any Singapore citizen or permanent resident aged ≥ 50 years is eligible to receive two FIT kits. Participants with at least one positive FIT are referred for further evaluation. We aimed to analyse the results of SCS data from the year 2008.</p><p><b>METHODS</b>The factors evaluated included compliance, positive test rate (PR) and positive predictive value (PPV) of FIT.</p><p><b>RESULTS</b>20,989 participants received 41,978 kits in 2008. Compliance was 38.9%, with 8,156 participants returning at least one kit. 8% of participants tested positive, and 75% of these test-positive participants agreed to undergo further investigations. 33 participants had colorectal cancers, 45 had advanced polyps (≥ 1 cm) and 90 had polyps < 1 cm. Histologically, 114 polyps were adenomatous, 20 were hyperplastic and 1 was serrated. PPV of colorectal neoplasia for those who underwent further colonoscopy was 34%. Over half of the participants who had only one positive test had colorectal neoplasia.</p><p><b>CONCLUSION</b>PR and PPV of FIT in our study were comparable to that in the literature. However, compliance was low and a quarter of all participants who tested positive refused further investigations. Extensive population education programmes are required to improve compliance and tackle inhibitions among the masses. It is also important to take steps to enhance the cost effectiveness of future screening programmes.</p>