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Human sulfotransferase (SULT) 1A1 pharmacogenetics: Intragene haplotype, breast cancer and mammographic breast density
Author(s) -
Adjei A.,
Olson J.,
Vachon C.,
Vierkant R.,
Pankratz V.,
Brandt K.,
Fredericksen Z.,
Sellers T.,
Weinshilboum R.
Publication year - 2005
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2004.12.259
Subject(s) - pharmacogenetics , breast cancer , haplotype , mammographic density , mammography , medicine , oncology , sulfotransferase , cancer , allele , genetics , gene , genotype , biology , sulfation
Background/Aims SULT1A1 catalyzes the sulfate conjugation of estrogens and many drugs. A common ORF SNP (Arg213His, SULT1A1*2 ) is associated with low SULT1A1 activity, and 2 additional SNPs, C(‐624)G and G(‐396)A, are associated with decreased transcription. Methods We examined the association of these 3 SNPs with breast cancer (BC) in 173 relatives of BC cases and 330 control subjects, and with percent mammographic density (PD) in 357 control postmenopausal women. Results Women with 2 copies of any one of the 3 SULT1A1 variant SNPs were at approximately 50% higher risk of breast cancer[for (−624) OR=1.7, CI=0.9–3.1; for (−396) OR=1.6, CI=0.9–2.8; for Arg213His OR=1.5, CI=0.8–2.7]. Haplotype analysis showed increased risk of BC for those with all 3 SNPs (OR= 1.4, CI=0.9–2.0). Significant increases in PD were also observed for carriers of the (−396) SNP[mean PD=18%, 20%, 23% for 0, 1, 2 copies, respectively, p<0.01]. Conclusions These data suggest that intragene haplotype for SULT1A1 (−624)G, (−396)A and Arg213His may be associated with increased breast cancer risk, and the (−396) SNP with increased PD. Clinical Pharmacology & Therapeutics (2005) 77 , P96–P96; doi: 10.1016/j.clpt.2004.12.259