Colorectal cancer in South Asians in UK and the role of recessive mutations

Abstract

Aims: 1. To examine the rate of incidence of colorectal cancer (CRC) in the South Asian (SA) population in UK. 2. To examine the hypothesis that recessive mutations contribute to susceptibility to CRC among SA, in view of consanguinity in the family. Methods: 1. SA cases from Bradford were identified from data on CRC from NYCRIS from 1997-2004 based on post code and incidence rate calculated using data from the 2001 census. 2. 59 cases of CRC were recruited from 5 hospitals in Yorkshire and 195 controls were recruited from the community. Blood / saliva samples were obtained together with family history. Genetic analysis was done to look for mutation R802X in PMS2, and Y165C and G382D in MYH genes. MREC approval was obtained for the study. Results: 1. Age standardized rate of incidence of CRC per 100,000 per annum in SA from Bradford was found to be 11.4, which is nearly twice the rate in South Asia, but 1/3 the rate for Caucasians. 2. All families of Pakistani origin had consanguineous marriages but none was found in Indians. 2 homozygous and 1 heterozygous cases for mutation R802X were found in PMS2. Single case of heterozygous variant leu786 met was found in exon 14 of PMS2. No mutation was found in MYH. Conclusion: The incidence of CRC has doubled in migrant SA population in UK compared with the rate in South Asia. Recessive mutations are likely to be a contributor to CRC in view of consanguineous marriages in this population.