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Polymorphisms in the CYP1A1 gene are associated with prostate cancer risk
Author(s) -
Chang Baoli,
Zheng Siqun L.,
Isaacs Sarah D.,
Turner Aubrey,
Hawkins Gregory A.,
Wiley Kathy E.,
Bleecker Eugene R.,
Walsh Patrick C.,
Meyers Deborah A.,
Isaacs William B.,
Xu Jianfeng
Publication year - 2003
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.11249
Subject(s) - haplotype , single nucleotide polymorphism , genotype , allele , genetics , biology , snp , proband , case control study , medicine , allele frequency , gene , mutation
CYP1A1 is likely to play an important role in the etiology of CaP through its function in activating environmental procarcinogens and catalyzing the oxidative metabolites of estrogens. To test the hypothesis that genetic polymorphisms in the CYP1A1 gene may be associated with the risk for CaP, we compared the allele, genotype and haplotype frequencies of 3 SNPs (3801T>C, 2455A>G and 2453C>A) of CYP1A1 among 159 HPC probands, 245 sporadic CaP cases and 222 unaffected men. Two SNPs (3801T>C and 2455A>G) were each individually associated with CaP risk when the allele and genotype frequencies were compared between CaP patients and unaffected controls. Furthermore, a combined SNP analysis using a haplotype approach revealed an even stronger association in Caucasians. Specifically, 4 major haplotypes (T‐A‐C, C‐A‐C, C‐G‐C and T‐A‐A) accounted for 99.8% of all observed haplotypes. These 4 haplotypes correspond to the previously described nomenclature ( CYP1A1 *1A, CYP1A1 *2A, CYP1A1 *2B and CYP1A1 *4). The frequencies of these 4 haplotypes were significantly different among CaP patients and controls. The haplotype T‐A‐C ( CYP1A1 *1A) was significantly associated with increased risk for CaP, and the haplotype C‐A‐C ( CYP1A1 *2A) was significantly associated with decreased risk for CaP. These findings suggest that genetic polymorphisms in CYP1A1 may modify the risk for CaP. © 2003 Wiley‐Liss, Inc.