Genetic variants of CYP19 (aromatase) and breast cancer risk
Genetic variants of CYP19 (aromatase) and breast cancer risk
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DOI：
10.1038/sj.onc.1203425
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发表时间：
2000-03-02
期刊：
影响因子：
8
通讯作者：
Borresen-Dale, AL
中科院分区：
文献类型：
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作者：
Kristensen, VN;Harada, N;Borresen-Dale, AL
研究了CYP 19外显子10中SNP对肿瘤mRNA水平和剪接变体的影响，并与临床参数和乳腺癌风险相关。在绝大多数乳腺癌中，雌激素水平调节肿瘤生长并依赖于CYP 19的活性。在单一测序反应（SSR）中通过T-轨迹对患者（n=481）和对照（n=236）进行基因分型，TT基因型的频率在患者组显著高于对照组（P=0.007）尤其是在III期和IV期疾病患者中（P=0.004）和肿瘤大于5 cm（P=0.001），肿瘤中芳香化酶mRNA水平与T等位基因的存在显著相关（P=0.018），以及从脂肪启动子到卵巢启动子的转换（P=0.004）。此前，我们报道了CYP 19的一种罕见多态性等位基因（重复（TTTA）（12））在乳腺癌患者中的频率显著高于对照组，这里我们描述了另一种多态性，CYP 19基因外显子10中的C-T取代，其与（TTTA）n多态性处于强连锁不平衡，但具有更高的变异等位基因频率，我们的数据表明，T-等位基因的CYP 19基因与“高活性”表型。
The effect of a SNP in exon 10 of CYP19 on tumor mRNA levels and splice variants were studied and correlated with clinical parameters and risk of breast cancer. In the vast majority of breast cancers, the estrogen levels modulate the tumor growth and depend on the activity of CYP19, Patients (n=481) and controls (n=236) were genotyped by T-tracks in a single sequencing reaction (SSR), The frequency of TT genotypes was significantly higher in patients versus controls (P=0.007) particularly among those with stage III and IV disease (P=0.004) and with tumors larger than 5 cm (P=0.001), A significant association between presence of the T allele and the level of aromatase mRNA in the tumors was observed (P=0.018), as well as with a switch from adipose promoter to ovary promoter (P=0.004). Previously, we reported a rare polymorphic allele of CYP19 (repeat (TTTA)(12)) to be significantly more frequent in breast cancer patients than in controls, Here we describe another polymorphism, a C-T substitution in exon 10 of the CYP19 gene which is in strong linkage disequilibrium with the (TTTA)n polymorphism but with higher frequency of the variant allele, Our data suggest that the T-allele of the CYP19 gene is associated with a 'high activity' phenotype.