SULT1A1 genotype and susceptibility to colorectal cancer

Abstract

Several procarcinogens that are present in cooked red meat and tobacco smoke are substrates for sulfotransferase 1A1 (SULT1A1). The association between environmental exposures and colorectal cancer risk may be modified by individual differences in the metabolism. Thus, we investigated the effect of a common polymorphism in the SULT1A1 gene associated with decreased enzyme activity on the susceptibility to colorectal cancer in a populationbased case-control study. Patients (505) and 604 age-and sexmatched controls provided detailed risk factor information and were genotyped for SULT1A1 G638A using a fluorescence-based melting curve analysis method. Multivariate logistic regression analysis was used to estimate colorectal cancer risk associated with environmental exposures by SULT1A1 genotype. SULT1A1 genotype was not an independent risk factor for colorectal cancer. Risk of colorectal cancer associated with frequent consumption of red meat was significantly elevated among carriers of the SULT1A1*2 allele but not increased among subjects with the SULT1A1*1/*1 genotype (odds ratio (OR) 2.1, 95% confidence interval (CI) 1.1-4.1 and OR 1.0, 95% CI 0.5-2.1, respectively). Colorectal cancer risk associated with 301 pack-years of active smoking was higher among carriers of the SULT1A1*2 allele (OR 1.7, 95% CI 1.0-3.2) than among individuals with the SULT1A1*1/*1 genotype (OR 1.1, 95% CI 0.6-2.1). Our results do not support a main effect of SULT1A1 genotype with regard to colorectal cancer but suggest that individuals with the low activity SULT1A1*2 allele may be at higher risk following carcinogen exposure than those with the SULT1A1*1/*1 genotype. ' 2006 Wiley-Liss, Inc.Key words: SULT1A1; genetic polymorphism; colorectal cancer; tobacco; meat Sporadic colorectal cancer is considered a multifactorial disease with both environmental and genetic factors contributing to individual risk. Environmental exposures that have been associated with an increased risk of colorectal cancer include consumption of red meat and long-term cigarette smoking.1,2 Both consumption of red meat cooked at high temperatures and tobacco smoking increase exposure to several potentially carcinogenic substances such as heterocyclic amines (HCAs), polycyclic aromatic hydrocarbons (PAHs) and N-nitroso compounds. 3,4 Sulfotransferase 1A1 (SULT1A1) is involved in the Phase IImetabolism of xenobiotics and is expressed in the liver as well as in many extrahepatic tissues including colonic mucosa.5,6 The SULT1A1-catalyzed transfer of a sulfo moiety to its substrates usually increases their water solubility and thus facilitates excretion. However, the reaction with SULT1A1 may also lead to bioactivation of certain substances.7 A common polymorphism in the human SULT1A1 gene (G638A), referred to as SULT1A1*2 allele, leads to an amino acid change (Arg 213 His) and has been associated with decreased activity of the respective allozyme. 8,9 Hence, genetically determined differences in detoxification and bioactivation of xenobiotics may alter individual exposu...

The association of SULT1A1 codon 213 polymorphism and breast cancer susceptibility: meta-analysis from 16 studies involving 23,445 subjects

“…The sulfonation of estrogens was catalyzed by SULT1A1 to form water-soluble and biologically inactive estrogen sulfates, which reducing the level of estrogen exposure in their target tissues [9,10]. Previous functional studies have demonstrated that the variant A allele is associated with significantly reduced sulfotransferase activity in platelets compared with the wild-type G allele [5,6] The relevant SULT1A1 Arg 213 His single-nucleotide polymorphism studies have shown that 213 His allele is linked to cancer susceptibility in several cancers [11][12][13][14][15]. The specific role of SULT1A1 codon 213 polymorphism in breast cancer susceptibility has been the research focus of numerous researches [11,[16][17][18][19][20][21][22][23][24][25][26][27][28][29][30].…”

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

“…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 .…”

Metabolism and toxicology of heterocyclic aromatic amines when consumed in diet: Influence of the genetic susceptibility to develop human cancer. A review

“…Taking into account the SULT1A1 genotype, a significant risk increase associated to frequent meat consumption is observed in carriers of the SULT1A1*2 allele while in subjects with the SULT1A1*1/*1 genotype no association is apparent (Lilla et al, 2006). This differential effect is pronounced in individuals consuming mostly fried/grilled meat or processed meat but not in those preferring boiled/stewed meat.…”