Association of the SULT1A1 R213H polymorphism with colorectal cancer.
1. Sulphotransferases are a superfamily of enzymes involved in both detoxification and bioactivation of endogenous and exogenous compounds. The arylsulphotransferase SULT1A1 has been implicated in a decreased activity and thermostability when the wild-type arginine at position 213 of the coding sequence is substituted by a histidine. SULT1A1 is the isoform primarily associated with the conversion of dietary N-OH arylamines to DNA binding adducts and is therefore of interest to determine whether this polymorphism is linked to colorectal cancer. 2. Genotyping, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis, was performed using DNA samples of healthy control subjects (n = 402) and patients with histologically proven colorectal cancer (n = 383). Both control and test populations possessed similar frequencies for the mutant allele (32.1 and 31%, respectively; P = 0.935). Results were not altered when age and gender were considered as potential confounders in a logistic regression analysis. 3. Examination of the sulphonating ability of the two allozymes with respect to the substrates p-nitrophenol and paracetamol showed that the affinity and rate of sulphonation was unaffected by substitution of arginine to histidine at position 213 of the amino acid sequence. 4. From this study, we conclude that the SULT1A1 R213H polymorphism is not linked with colorectal cancer in this elderly Australian population.
Wong
Chung Fai
CF
Department of Physiology and Pharmacology, University of Queensland, Princess Alexandra Hospital, St Lucia, Brisbane, Qld. 4102, Australia. fwong@cicr.uq.edu.au
Liyou
Nancy
N
Leggett
Barbara
B
Young
Joanne
J
Johnson
Anthony
A
McManus
Michael E
ME
D000368:Aged; D019943:Amino Acid Substitution / Q000235:genetics; D001120:Arginine / Q000235:genetics; D015239:Arylsulfotransferase; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006639:Histidine / Q000235:genetics; D006801:Humans; D016015:Logistic Models; D008297:Male; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000235:genetics*; D015238:Sulfotransferases / Q000235:genetics*
D006639:Histidine; D001120:Arginine; D015238:Sulfotransferases; D015239:Arylsulfotransferase; C117544:SULT1A1 protein, human