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

Abstract

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.

Case–control study and meta-analysis of SULT1A1 Arg213His polymorphism for gene, ethnicity and environment interaction for cancer risk

“…The role of SULT1A1 in the biotransformation of tobacco carcinogens and its association with lung cancer has been previously reported (Liang et al, 2004). There are reports of SULT1A1*2 association with increased risk for oesophageal cancers (Dandara et al, 2006) as well as gastric cancer (Boccia et al, 2005) in individuals who consume alcohol and smoke tobacco.…”

“…In contrast to the GST super family of enzymes that have been studied extensively for tobacco carcinogenesis (Nakajima et al, 1995;Cheng et al, 1999;Buch et al, 2002;Jhavar et al, 2004Jhavar et al, , 2005, other phase II metabolising enzymes such as the SULT have been less extensively studied (Hung et al, 2004;Dandara et al, 2006;Pachouri et al, 2006). There also has not been any collation of published data or a meta-analysis of case -control studies evaluating SULT enzyme in cancers.…”

“…There is a large body of evidence, including meta-analyses to support the association of various isoforms of glutathione-S transferases (GSTs), cytochrome P450 and N-acetyl transferase with tobacco carcinogenesis. Although sulphotransferase (SULT) enzymes could play an equally important role in detoxifying tobacco carcinogens, there are very few, mostly inconclusive, studies examining the association of genetic alteration in the genes coding for this super family of multifunctional enzymes with TRC (Seth et al, 2000;Hung et al, 2004;Sellers et al, 2005;Dandara et al, 2006). Sulphotransferase enzymes catalyse sulphation by transferring sulphonate (sulphuryl) group from cofactor 3 0 -phosphoadenosine 5 0 -phosphosulphate to a nucleophilic acceptor substrate to form either a sulphate ester or a sulphamate.…”

“…Of the various polymorphisms in SULT1A1, the Arg-His polymorphism at position 213, in exon 7 (SULT1A1*2), has a twofold lower catalytic activity and thermo stability than its high-activity Arg 213 counterpart as demonstrated in platelet cytosol (Raftogianis et al, 1997;Nowell et al, 2000;Nagar et al, 2006). Although several reports show risk association of the SULT1A1 variant with different cancers (Sun et al, 2005;Dandara et al, 2006;Pachouri et al, 2006;Fan et al, 2007;Lilla et al, 2007;Bardakci et al, 2008), others show either no effect (Sellers et al, 2005) or a protective effect .…”

Molecular Biology Character of Esophageal Cancer

“…ECRG1 (Arg290Gln) was identified as the susceptible SNP of ESCC . It has been found that the increased risk of ESCC relates to combined SULT1A12*2 genotype and CYP3A5 heterozygous genotypes, especially in tobacco smokers (Dandara et al, 2006). SNP of ATP-binding cassette sub-family B (MDR/TAP) member 1 gene (ABCB1) was reported to be associated with lymph node and distant metastases in EC (Narumiya et al, 2011).…”