THE SULT1A1 ALLELE WITH LOW POTENTIAL FOR ESTROGEN INACTIVATION IS ASSOCIATED WITH REDUCED COLORECTAL CANCER RISK IN POSTMENOPAUSAL WOMEN
Sterjev Z1*, Josifovski T2*, Panovski M2, Suturkova L1, Dimovski AJ1
*Corresponding Author: Professor Aleksandar J. Dimovski, M.D., Ph.D., Pharmacogenetic Laboratory, Institute for Pharmaceutical Chemistry, Faculty of Pharmacy, Vodnjanska 17, 1000 Skopje, Republic of Macedonia; Tel.: +389-2-3217-580; Fax: +389-2-3290-830; E-mail: adimovski@baba.ff.ukim.edu.mk * Contributed equally to this paper and should both be considered as first authors.
page: 43

Abstract

Sulfotransferases (SULTs) are a superfamily of enzymes involved in both detoxification and bioactivation of endogenous and exogenous compounds. A genetic polymorphism in the coding region of the SULT1A1 gene (Arg213His, CGC->CAC) has been associated with a modular phenotype, in which individuals with this allele have a substantially lower enzyme activity. Studies on the influence of this variant on susceptibility of colorectal cancer (CRC) have produced no definitive conclusion. We determined the allele frequency and genotype distributions of this variant in 100 sporadic colorectal cancer patients and 200 normal controls from the Republic of Macedonia. A significantly lower frequency of this allele was detected in the colorectal cancer patients compared to normal controls (0.27 vs. 0.37, respectively, p = 0.02). This was more pronounced in homozygotes [odds ratio (OR) 2.35] than in heterozygotes (OR 1.52), indicating that this variant is transmitted as a recessive trait. There was a significantly reduced risk of colon cancer only in women with the His213 genotypes and >60 years of age (p = 0.008; OR 3.46) but not in those with <60 years of age, or in men. No association was found with family history, localization, Dukesí stage or microsatellite instability (MSI) status. Our data indicate that the SULT1A1*His allele has a protective role for the development of CRC in women older than 60 years of age, most probably due to low potential for estrogen inactivation.
Key words: Sulfotransferas (SULT), Colorectal cancer, Predisposition.




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