COGENT (COlorectal cancer GENeTics): an international consortium to study the role of polymorphic variation on the risk of colorectal cancer.

It is now recognised that a part of the inherited risk of colorectal cancer (CRC) can be explained by the co-inheritance of low-penetrance genetic variants. The accumulated experience to date in identifying these variants has served to highlight difficulties in conducting statistically and methodologically rigorous studies and follow-up analyses. The COGENT (COlorectal cancer GENeTics) consortium includes 20 research groups in Europe, Australia, the Americas, China and Japan. The overarching goal of COGENT is to identify and characterise low-penetrance susceptibility variants for CRC through association-based analyses. In this study, we review the rationale for identifying low-penetrance variants for CRC and our proposed strategy for establishing COGENT.

Efficacy of combination chemotherapy with irinotecan (CPT-11) plus capecitabine in patients with metastatic or advanced colorectal carcinoma--a dual-centre phase II study: the MAC-6.

AIMS: A phase II trial was initiated to evaluate the efficacy and toxicity of combination chemotherapy with irinotecan (CPT-11) plus capecitabine in patients with metastatic colorectal cancer. PATIENTS AND METHODS: Patients received a combination of CPT-11 plus capecitabine. CPT-11 was infused intravenously on day 1 every 2 weeks and oral capecitabine was taken twice daily for 5 days every 7 days. Efficacy and toxicities were assessed. RESULTS: Between 2004 and 2005, 43 patients were enrolled. The overall response rate was 51.35%. With a median follow-up of 13 months, the median time to progression was 10 months (95% confidence interval 7.6-12.3 months); the median survival was 15 months (95% confidence interval 13.9-16.9 months). The most common grade 3 haematological and non-haematological toxicities were neutropenia (5.4%), diarrhoea (8.1%) and hand-foot syndrome (2.7%). CONCLUSIONS: CPT-11 plus capecitabine with a 14 day cycle showed a comparable response with international phase II data with a 3 weekly regimen and was well tolerated as a first-line palliative chemotherapy in patients with metastatic colorectal cancer. The data should be interpreted with caution due to the limited sample size and should be further confirmed by a phase III randomised trial.

Phenotype and management of patients with familial adenomatous polyposis in Hong Kong: perspective of the Hereditary Gastrointestinal Cancer Registry.

OBJECTIVES: To report on the phenotypic spectrum and clinical management of Chinese patients suffering from the rare autosomal dominant colorectal cancer syndrome of familial adenomatous polyposis. DESIGN: Analysis of prospectively collected data from the database of a regional registry. SETTING: The Hereditary Gastrointestinal Cancer Registry, Hong Kong. PARTICIPANTS: One hundred and eight patients with proven familial adenomatous polyposis from 36 local Chinese families with the condition recruited to the Registry from 1995 to 2001. INTERVENTIONS: Screening programme for at-risk family members, prophylactic surgery at presymptomatic diagnosis, and surveillance programme for extracolonic lesions in affected individuals. MAIN OUTCOME MEASURES: Rate of colorectal cancer, type of surgical treatment, spectrum of extracolonic lesions, and management of the syndrome. RESULTS: Fifty patients suffered from colorectal cancer with a mortality rate of 78.0%. The strategy of presymptomatic diagnosis by screening and appropriate prophylactic surgery reduced the incidence of colorectal cancer. Affected individuals were prone to develop potentially serious extracolonic lesions including thyroid cancer (5.7%), desmoid tumour (15.7%), gastroduodenal adenomas (7.1%), duodenal microadenoma (17.1%), and pouch polyposis (17.4%). CONCLUSIONS: Screening and prophylactic surgery are effective ways to prevent colorectal cancer for patients with familial adenomatous polyposis. Lifelong regular surveillance is necessary to detect and manage extracolonic lesions. A dedicated registry is essential to coordinate clinical management and to compile data for furthering knowledge of this rare but complex syndrome.