Journal Article

Gene–environment interaction: the role of SULT1A1 and CYP3A5 polymorphisms as risk modifiers for squamous cell carcinoma of the oesophagus

Collet Dandara, Dong-Ping Li, Gabi Walther and M.Iqbal Parker

in Carcinogenesis

Volume 27, issue 4, pages 791-797
Published in print April 2006 | ISSN: 0143-3334
Published online November 2005 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgi257
Gene–environment interaction: the role of SULT1A1 and CYP3A5 polymorphisms as risk modifiers for squamous cell carcinoma of the oesophagus

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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.

Keywords: AOR, adjusted odds ratios; CB, commercial beer; HB, home brewed beer; WS, wine and spirits; OC, oesophageal cancer; PCR, polymerase chain reaction; RFLP, restriction fragment length polymorphism; SCC, squamous cell carcinoma

Journal Article.  5675 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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