Colorectal cancer (CRC) is the third leading cause of cancer death in the world [1]. A large body of evidence indicates that several dietary (red meat, processed meat, refined carbohydrates) and lifestyle (physical inactivity) factors may have a major influence on the risk of colon cancer [2]. In addition to the environment, genetic predisposition has a significant role in the etiopathogenesis of the disease. Two autosomal dominant syndromes, familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC), have been characterized in detail [3], and more than 20 low penetrance genes have been implicated in colorectal carcinogenesis [4]. Their contribution to the increased risk of CRC varies in different reports, and it appears that different sets of polymor­phisms and specific environmental factors peculiar to each population may promote colorectal carcinogenesis.
Sulfotransferases (SULTs) are a superfamily of enzymes involved in both detoxification and bioactivation of endogenous and exogenous compounds [5]. They catalyze the conjugation of sulfates to many phenolic or catehol drugs and other xenobiotics as well as endogenous compounds such as estrogens [6,7]. Human aryl SULT is expressed in various tissues in the body, including the liver, gastrointestinal tract, kidney, brain and lung [8-10]. In humans, there are three highly homologous phenol SULTs (SULT1A1, SULT1A2 and SULT1A3) whose genes are tightly linked on chromosome 16p12.1-p11.2 [11]. The major form in adult humans is the product of the SULT1A1 gene that is almost ubiquitous but particularly prevalent in the liver and intestine, including the colon [10].
A polymorphism in the coding region of the SULT1A1 gene [codon 213 (CGC->CAC) (Arg->His)] is associated with decreased activity and thermostability [12]. Bamber et al. [13] reported that the SULT1A1*Arg allele is associated with reduced colorectal cancer risk, but Sachse et al. [14], Wong et al. [15], Peng et al. [16], Nowell et al. [17] and Moreno et al. [18] found no association of polymorphisms in the SULT1A1 with colorectal cancer.
We have investigated the association between the SULT1A1 Arg213His variant and colorectal cancer in patients from the Republic of Macedonia.