Alcoholic cirrhosis but not alcoholic chronic pancreatitis is associated with ADH3*2/*2 and perhaps with ADH2*1/*1. Both genes encode less active alcohol-metabolizing enzymes that may be associated with cirrhosis because of delayed formation of acetaldehyde (with higher intakes of alcohol), or diversion of alcohol metabolism through pathways other than ADH.

No strong associations have been found between metabolic genotypes and colorectal cancer risk in Australia. Large studies will be required to confirm weak associations and to establish relationships between cancer risk, metabolic genotypes and exposure to dietary or other environmental carcinogens.

Summary Expression of Fas, an apoptosis-inducing receptor, in colonic epithelium is progressively reduced during malignant transformation. We have examined the human Fas gene for loss of heterozygosity (LOH) and gross rearrangements in colon tumours and matched normal mucosa. Polymerase chain reaction (PCR) primers were designed to span a Dral restriction fragment length polymorphic site in the gene. Heterozygosity was detected in normal DNA samples by PCR amplification of the polymorphic site and restriction enzyme digestion. Thirtyeight of 88 patients (43%) with colon carcinomas were informative for the assay, and LOH was detected in 6 of the 38 (16%) corresponding tumours. Tumours from three patients with LOH did not express detectable Fas mRNA, and Fas expression was reduced or absent in 7 of 11 tumours from informative patients without LOH. Southern blotting of tumour DNA samples was used to detect rearrangement of the Fas gene, but no altered hybridization patterns were observed in 64 tumours analysed. These findings indicate that disruption of the Fas gene is not primarily responsible for the loss of Fas protein expression reported in colon cancer. We have also shown that loss of Fas gene transcription is common in these tumours, which may be due to epigenetic gene silencing.

No abstract