Lynch syndrome in a predominantly Afrocentric population: a clinicopathological and genetic study

Colorectal cancer (CRC) is the third most commonly diagnosed cancer in men and women and is the fourth leading cause of cancer deaths in Jamaica.1,2 These proportions are comparable to those in the United States, where CRC is the third most common cancer diagnosed in men and women and the second leading cause of cancer-related death.3 Cancer is projected by the World Health Organization to replace chronic cardiovascular noncommunicable diseases as the leading cause of deaths in Western countries in the next 2–3 decades. In Jamaica, this is already the case, with the most recent report of the Ministry of Health recognizing cancer as the leading cause of death.2 Recent trends in CRC incidence and mortality in the United States reveal declining rates, which have been attributed to the effect of CRC screening and prevention through polypectomy as well as early detection and improved treatment.3 This is not the case in Jamaica, as the most recent statistics from the Jamaica Cancer Registry indicated a 25% increase in the incidence of CRC in men for the 2003–2007 period compared with the 1998–2002 period.4 The Jamaica Cancer Registry records the incidence for all cancers in the metropolis of Kingston and St. Andrew and extrapolates the data for all of Jamaica. There is no CRC registry for hereditary CRC in Jamaica. Whereas there are recommendations for screening for CRC in the Jamaican population,5 there are no organized national programs, and screening is largely opportunistic with individual variation. Colonoscopy is the screening method of choice and is the required method in patients with a positive alternative screening test. Despite the acknowledged disease burden, given the cost and the limited availability of colonoscopy, it is unlikely that a national screening program for CRC will be implemented in the near future. The mean age at CRC diagnosis in Jamaican patients is 65.5 years, but about 5.4% are younger than 40 years old.6 Most patients (60%) present with advanced CRC, with regional or distant metastases.6 The prognosis for advanced-stage disease is poor, with patients requiring expensive adjuvant therapy to improve survival or therapy with palliative intent. This can account for a significant portion of the health budget as the prevalence of the disease increases. Most patients with CRC will have sporadic CRC; however, about 15%–30% of patients under age 50 years will have a familial cancer syndrome,7,8 such as familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC) or at least a family history of first-degree relatives with the disease. The frequency of HNPCC in our population is unknown, as the necessary confirmatory tests are largely unavailable. Identification of patients with a familial susceptibility to CRC is important, as at-risk family members will benefit from intensive endoscopic surveillance, prophylactic surgery and possibly chemoprevention. There may also be implications for adjuvant chemotherapy, as some studies suggest that patients with defective mismatch repair (MMR) genes may not benefit from flurouracil-based adjuvant chemotherapy.9,10 Recognizing these syndromes also has an impact on referral for predictive genetic testing where identifying gene carriers improves the efficiency of cancer surveillance and helps to identify family members who require more frequent endoscopy versus those who can receive standard care.11 There are currently no registries or facilities available in Jamaica that target at-risk groups or provide genetic testing for high-risk patients. Whereas young patients with CRC in developed countries have been shown to have a relatively high incidence of mutations in their DNA MMR genes, the prevalence of these mutations in the young Jamaican CRC population is unknown. Our patients are predominantly of African descent and appear to have different tumour characteristics than other groups.12 The possibility of as-yet undiscovered genetic defects exists,13 and elucidation of these may lead to the identification of new at-risk groups, ultimately allowing earlier diagnosis of and improved outcomes of CRC in young patients in Jamaica.