Polymorphisms in the human aromatase cytochrome P450 gene (CYP19) and breast cancer risk
Polymorphisms in the human aromatase cytochrome P450 gene (CYP19) and breast cancer risk
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DOI：
10.1093/carcin/21.2.189
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发表时间：
2000-02-01
期刊：
影响因子：
4.7
通讯作者：
Ponder, BAJ
中科院分区：
文献类型：
--
作者：
Healey, CS;Dunning, AM;Ponder, BAJ
芳香酶在雌激素生物合成途径中催化雄激素向雌激素的转化。由于雌激素暴露增加被认为是乳腺癌的危险因素，因此人类芳香酶基因 (CYP19) 似乎是 Pow 外显性乳腺癌易感性的候选基因，初步报告表明 TTTA 重复的特定等位基因可能与乳腺癌风险差异相关。我们在 CYP19 基因中发现了两个新的多态性：内含子 4 中的 TCT 插入/删除和内含子 6 中的 G-->T 替换，这两个基因在英国人群中的等位基因频率分别为 0.35 和 0.45。我们在英国东盎格利亚人群中的多达 599 例乳腺癌病例和 433 例正常对照中对这些等位基因频率与 TTTA 重复频率进行了比较。我们发现这三个位点的等位基因之间存在很强的连锁不平衡，但任何等位基因与乳腺癌风险没有显着关联。观察到的最大比值比为： 内含子 4 TCT 插入/缺失多态性 [del/del 与 ins/ins] 为 1.03 (95% CI 0.68-1.55)；内含子 4 [TTTA]lo 等位基因为 1.56 (95% CI 0.63-3.83)；内含子 6 G-->T 多态性 [TT 与 GG] 为 1.29 (95% CI 0.75-2.21)，我们得出结论，CYP19 基因在英国人群中常见乳腺癌发病率中没有主要作用。
The aromatase enzyme catalyses the conversion of androgens to oestrogens in the oestrogen biosynthesis pathway. Because increased exposure to oestrogens is considered to be a risk factor for breast cancer, the human aromatase gene (CYP19) is a plausible candidate for Pow penetrance breast cancer susceptibility, Preliminary reports have suggested that specific alleles of a TTTA repeat may be associated with differences in breast cancer risk. We have identified two new polymorphisms in the CYP19 gene: a TCT insertion/deletion in intron 4 and a G-->T substitution in intron 6, which have rare allele frequencies of 0.35 and 0.45, respectively, in the British population, Comparison was made between the frequencies of these alleles and those of the TTTA repeat in up to 599 breast cancer cases and 433 normal controls from the East Anglian, British population. We found strong linkage disequilibrium between the alleles of these three loci, but no significant association of any alleles with breast cancer risk. The maximum odds ratios observed were: 1.03 (95% CI 0.68-1.55) for the intron 4 TCT insertion/deletion polymorphism [del/del versus ins/ins]; 1.56 (95% CI 0.63-3.83) for the intron 4 [TTTA]lo allele; 1.29 (95% CI 0.75-2.21) for the intron 6 G-->T polymorphism [TT versus GG], We conclude that the CYP19 gene has no major role in common breast cancer incidence in the British population.