Human sulfotransferases (SULTs) catalyze the conjugation of sulfate groups to a variety of endogen and exogenous substrates, including many drugs, neurotransmitters, thyroid and steroid hormones and pro-carcinogenic agents (1,2). SULTs are genetically polymorphic and are expressed in a wide variety of tissues, such as the liver, lung, brain, kidney, and platelets (3). To date, 13 human cytosolic SULT isoforms have been identified and grouped as four major families: SULT1, SULT2, SULT4 and SULT6 (4). The SULT1A1 gene mapped to chromosome 16p12.1-p11.2 encodes four different allozymes: SULT1A1^*1 (wild-type), SULT1A1^*2, SULT1A1^*3 and SULT1A1*4. The SULT1A1 enzyme catalyzes the sulfation of certain carcinogenic and mutagenic compounds including heterocyclic and aromatic amines, and polycyclic aromatic hydrocarbons (2). A genetic polymorphism in exon 7 of the SULT1A1 gene at the nucleotide of 638 (codon 213), results in a substitution of histidine by arginine (Arg²¹³His). SULT1A1^*2 (His²¹³ allele) is associated with less enzymatic activity and thermal stability compared with the wild-type allele (Arg²¹³ allele) in platelets (5,6).

Prostate cancer, a serious health problem in the Western world and Turkey, has shown an increasing incidence over the last decade (7). Some reports suggest that the risk of prostate cancer development is influenced by both genetic and environmental factors, such as diet, hormone levels, drinking habit, ethnicity and genetic background (8). It has been suggested by researchers that the SULT1A1 Arg²¹³His polymorphism may affect an individual’s capacity in the metabolism of numerous endogenous and exogenous compounds consequently resulting in the susceptibility of an individual to cancer (2). Studies have demonstrated the relationship between genetic polymorphisms of SULT1A1 Arg²¹³His and several cancer types including prostate cancer (9–16). On the other hand, the findings of these studies remain controversial. This study investigated, for the first time, the relationship between the SULT1A1 Arg²¹³His polymorphism and prostate cancer susceptibility in a Turkish population.

Demographic characteristics of the cases and controls are summarized in Table I. Mean ages of the cases and controls were 65.2±13.2 years (range, 42–88) and 61±11.4 years (range, 41–82), respectively. No significant relationship was found between the cases and controls in terms of smoking status (P=0.83). Mean PSA levels were 3.4±0.5 and 30.6±11.2 ng/ml in the controls and patients, respectively.

SULT1A1 Arg²¹³His allele and genotype frequencies are indicated in Table II. The genotype and allele frequencies were found to be in Hardy-Weinberg equilibrium. In the cases, the frequencies of the homozygous wild-type genotypes (Arg/Arg²¹³), the heterozygous genotype (Arg/His²¹³) and the homozygous variant genotype (His/His²¹³) were 52.8, 36.6 and 10.6%, respectively; in the controls, these frequencies were 60.3, 35.8 and 3.9%, respectively.

The risk of prostate cancer in individuals carrying the His²¹³ allele was determined by combining Arg/His²¹³ and His/His²¹³ genotypes. No statistically significant difference was found between the cases and controls in comparison of the genotype combination (P=0.24; OR, 1.36; 95% CI, 0.84–2.25). Concerning the smoker and non-smoker populations, no significant relationship was evident between the case and control groups regarding genotypic combinations (P=0.45; OR, 1.32 and P=0.34; OR, 1.39, respectively) (Table III).

The incidence of prostate cancer displays large ethnic variations worldwide. While the lowest incidence rate of prostate cancer is observed for Chinese men, African-American men have the highest rate of incidence (7). It is believed that advanced age, an intact androgen metabolism, ethnicity and genetic background are risk factors for prostate cancer development (8). The majority of studies suggest that genetic polymorphisms in xenobiotic metabolizing enzymes may play an important role in the susceptibility of individuals to cancer (18). In our previous study, we found that the GSTM1 null genotype may play an important role as a risk factor for prostate cancer development in the Turkish population (14).

Allelic frequencies of the His²¹³ allele differ ranging from 5 to 32% among ethnic populations (5,19,20). The frequency of the His²¹³ allele was reported to be 18.5 and 22% in a study of a Turkish population (21,22). In the present study, the frequency of this allele in the control population was determined to be 21.9% which was higher than the frequency in Chinese, Taiwanese and Koreans while lower than the frequency reported for Caucasian and Nigerian populations (5,19,20). Distributions of the SULT1A1 Arg²¹³His genotypes and alleles were also not significantly different between the cases and controls in the present study.

In many studies, a significant relationship has been demonstrated between the His²¹³ allele and various cancer types, including gastric, lung, colorectal, and breast (9,10,13,21). In addition, a statistical significant association was noted between the His²¹³ allele and primary brain tumor and lung cancer incidence in our previous studies (21,22). However, in the present study, no significant relationship was determined between the His²¹³ allele and prostate cancer although His²¹³ allele frequencies were higher in the patients than in the controls. Another study which is in agreement with ours was reported by Steiner et al (15). In contrast, Nowell et al (11) found a positive association between the Arg²¹³ allele (rapid sulfation allele) and prostate cancer risk. These controversial results may be due to the dual role (bioactivation and detoxification) of SULT1A1 in the metabolism of various carcinogens (23). Although SULT1A1 is considered as a phase II enzyme, it has been demonstrated that this enzyme acts to bioactivate various pro-carcinogens and pro-mutagens such as dietary carcinogen 2-amino-1-methyl-6-phenyl-imidazo (4,5-b) pyridine which induces prostate tumors in rats (24). Chou et al (25) and Ozawa et al (26) found that SULT1A1 catalyzes the sulfation of N-hydroxy derivates of arylamines and heterocyclic amines, to form more reactive DNA adduct-forming compounds. In this context, differing environmental parameters may also influence the function of a given allele. Thus, a different genetic background and different carcinogen exposure may play an important role in the different risk estimates associated with polymorphisms. In light of this knowledge, we believe that the influence of the SULT1A1 polymorphism on cancer development risk may differ according to the type of exposed carcinogen.

In the present study, there was no statistically significant association between the SULT1A1 Arg²¹³His polymorphism and smoking status of the study population which is in accordance with previously published studies (21,22).

In summary, our results suggest that the SULT1A1 Arg²¹³His polymorphism does not play a role in prostate cancer susceptibility in the Turkish population. However, since this study is the first report carried out in a Turkish population, it may contribute to the understanding of the relationship between the SULT1A1 polymorphism and prostate cancer. In order to elucidate the role of genetic polymorphisms in carcinogen metabolizing enzymes in prostate cancer development more accurately, environmental exposure to specific carcinogens must be investigated in larger studies.