Narrow Results

There is now an improved ability to detect people at high risk of cancer through analysis of their family history and genetic testing. Advances in cancer screening, cancer surveillance and cancer prevention have accompanied this. It is important to identify individuals at high cancer risk so that these advances can be applied in their management. Equally important is the identification of those not at high risk, so that they are spared unnecessary cancer screening and concern. Risk assessment and genetic testing is available through familial cancer services. This article introduces the common syndromes requiring referral to such a service and the general principles of cancer genetic testing.

Familial adenomatous polyposis (FAP) is a familial form of colon cancer caused by mutation of the adenomatous polyposis coli (APC) gene. We investigated the APC mutation and phenotypic spectrum in 172 members of 36 Singapore FAP families. The protein truncation test (PTT) and DNA sequencing were used to screen the entire APC coding region for germline mutations. APC mutations were found in 28 families (78 %). 65 patients tested positive while 63 non-affected members tested negative. The correlation of PTT to clinical diagnosis is therefore 100%, suggesting that PTT is a highly reliable presymptomatic test for FAP. Twenty different APC mutations were identified, eleven of those were novel. All mutations, except one, resulted in the classical colonic phenotype. Interestingly, mutation at codon 332 resulted in attenuated FAP with left-sided predominance of polyps rather than the right. For the eight families without APC mutations, we screened for β-catenin mutation which was shown to be able to substitute for APC mutation in sporadic colorectal cancer. No germline β-catenin mutation was found. Further analysis reveals atypical clinical features such as the co-existence of adenomatous and hyperplastic polyps and other non-FAP associated cancers in these patients. Our results suggest the involvement of other genes and possibly new variants for the polyposis syndrome.