Cancer of the proximal digestive tract is associated with tobacco
smoke and
ethanol exposure. The
UDP-glucuronosyltransferase (UGT) 1A7 is a detoxifying
enzyme capable of tobacco-borne
carcinogen detoxification and cellular protection and has been implicated as a
cancer risk gene. In this study, UGT1A7 expression is demonstrated in oral, esophageal, and gastric tissue, which are the principle sites of proximal digestive tract
cancer. Genomic
DNA from the blood of 76 patients with esophageal, orolaryngeal and
gastric cancer as well as from 210 healthy blood donors was analysed for the presence of UGT1A7 polymorphisms by sequencing and temperature gradient gel electrophoresis. Wild type UGT1A7 alleles were equally distributed between controls (19 %) and
cancer patients (22 %). However, the UGT1A7*3 allele combining W208R, N129K and R131K missense mutations and exhibiting substantially reduced
carcinogen detoxification activity was significantly associated with proximal
gastrointestinal cancer and identified as a risk allele present in 32 % of
cancer patients and 19 % of controls (P = 0.0008, OR 2,02 (95 %-CI 1.33-3.07)). We identify the significant association of the UGT1A7*3 allele encoding a low catalytic activity
protein as a risk gene in proximal digestive tract
cancer and as a potential marker for
cancer susceptibility.