Chang Bao-li, 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
Center for Human Genomics, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157 USA.
Int J Cancer. 2003 Sep 1;106(3):375-8. doi: 10.1002/ijc.11249.
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 (CYP1A11A, CYP1A12A, CYP1A12B and CYP1A14). The frequencies of these 4 haplotypes were significantly different among CaP patients and controls. The haplotype T-A-C (CYP1A11A) was significantly associated with increased risk for CaP, and the haplotype C-A-C (CYP1A12A) was significantly associated with decreased risk for CaP. These findings suggest that genetic polymorphisms in CYP1A1 may modify the risk for CaP.
细胞色素P450 1A1（CYP1A1）可能通过激活环境前致癌物和催化雌激素的氧化代谢产物，在前列腺癌（CaP）的病因学中发挥重要作用。为了验证CYP1A1基因的遗传多态性可能与CaP风险相关这一假设，我们比较了159例遗传性前列腺癌（HPC）先证者、245例散发性CaP患者和222例未受影响男性中CYP1A1的3个单核苷酸多态性（SNP）（3801T>C、2455A>G和2453C>A）的等位基因、基因型和单倍型频率。当比较CaP患者和未受影响对照组之间的等位基因和基因型频率时，两个SNP（3801T>C和2455A>G）各自单独与CaP风险相关。此外，使用单倍型方法的联合SNP分析显示在白种人中关联更强。具体而言，4种主要单倍型（T-A-C、C-A-C、C-G-C和T-A-A）占所有观察到的单倍型的99.8%。这4种单倍型对应于先前描述的命名法（CYP1A11A、CYP1A12A、CYP1A12B和CYP1A14）。这4种单倍型的频率在CaP患者和对照组之间存在显著差异。单倍型T-A-C（CYP1A11A）与CaP风险增加显著相关，而单倍型C-A-C（CYP1A12A）与CaP风险降低显著相关。这些发现表明CYP1A1基因的遗传多态性可能改变CaP的风险。
