Gene-environment interaction: the role of SULT1A1 and CYP3A5 polymorphisms as risk modifiers for squamous cell carcinoma of the oesophagus.
An imbalance in the activities of enzymes involved in the metabolism, conjugation and transport of xenobiotics may account for the variability in susceptibility to the development of complex diseases such as cancer between different population groups. In this study we investigated a functional polymorphism in the SULT1A1 gene in 245 patients and 288 controls. Previous studies have shown that the 638G-->A polymorphism that results in the substitution of arginine by histidine at codon 213 (SULT1A1*2) results in decreased SULT1A1 activity. The same group of samples used in this study had been previously genotyped for CYP3A5 genetic polymorphisms. Among Black subjects the burning of wood or charcoal for cooking and keeping warm was significantly associated with increased risk for oesophageal cancer (OC) (AOR, 15.2; P=0.001) as was the consumption of home-brewed beer (AOR, 6.97; P=0.0001). Among the Mixed Ancestry group, tobacco smoking combined with alcohol consumption were significantly associated with higher risk for OC (AOR, 5.18; P=0.0005). In both Blacks and Mixed Ancestry subjects, starting to smoke below the age of 20 years was associated with significantly increased risk for OC (AOR, 3.5 among the Blacks and AOR, 12 among the Mixed Ancestry). The homozygous SULT1A1*2/*2 genotype was associated with increased risk for OC among smokers. The SULT1A1*2/*2 genotype in combination with the CYP3A5 heterozygous genotypes was associated with significantly increased risk for OC (AOR, 3.60; P=0.001) with the risk being even higher among smokers compared with non-smokers. The above findings confirm the association between alcohol consumption and tobacco smoking with increased risk for OC. The genotype results show that SULT1A1*2/*2 genotype is associated with increased risk for OC among subjects exposed to tobacco-smoke-related carcinogens.
Dandara
Collet
C
UCT/MRC-Oesophageal Cancer Research Group, Division of Medical Biochemistry, Institute of Infectious Disease and Molecular Medicine (IIDMM), Groote Schuur Hospital, Faculty of Health Sciences, University of Cape Town, South Africa.
Li
Dong-Ping
DP
Walther
Gabi
G
Parker
M Iqbal
MI
D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects; D015239:Arylsulfotransferase / Q000235:genetics* / Q000378:metabolism; D044383:Black People / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D003296:Cooking; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000209:etiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012906:Smoke; D012907:Smoking / Q000009:adverse effects; D013019:South Africa
D012906:Smoke; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D015239:Arylsulfotransferase; C117544:SULT1A1 protein, human