A family-based genetic association study of variants in estrogen-metabolism genes COMT and CYP1B1 and breast cancer risk
A family-based genetic association study of variants in estrogen-metabolism genes COMT and CYP1B1 and breast cancer risk
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DOI：
10.1023/b:brea.0000025401.60794.68
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发表时间：
2004-05-01
影响因子：
3.8
通讯作者：
Santella, RM
中科院分区：
文献类型：
--
作者：
Ahsan, H;Chen, Y;Santella, RM
在本文中，我们报告了一项基于家族的关联研究的结果，该研究检查了两个关键的雌激素代谢基因CYP 1B 1（密码子432 G -> C和密码子453 A -> G变体）和COMT（密码子158 G）多态性之间的关联。变异）和女性乳腺癌。我们在280个核心家庭中进行了这项研究，其中包含一个或多个患有乳腺癌的女儿，共有1124名家庭成员（702名有宪法DNA和问卷数据，421名没有）。这些核心家庭是从参加大都会纽约登记处（MNYR）的乳腺癌家庭中选出的，MNYR是NCI乳腺合作家庭登记处的六个中心之一。我们使用基于似然的统计方法来检查等位基因关联。我们没有发现CYP 1B 1和COMT基因的变异等位基因与乳腺癌在这些家庭。这与使用这些家庭中所有可用同胞的匹配病例对照分析结果一致。然而，我们发现CYP 1B 1密码子453变异G等位基因和COMT密码子158变异A等位基因的父母携带状态与女儿患乳腺癌的风险相关（独立于女儿自己的基因型）。总之，这项以家庭为基础的研究结果表明，女性自身的CYP 1B 1或COMT基因型与其乳腺癌风险无关。虽然这项研究发现，某些CYP 1B 1或COMT基因型的父母携带者状态可能与女儿的乳腺癌风险有关，但这一发现的生物学基础和独立确认需要在未来更大的以家庭为基础的研究中进行调查，然后才能做出有意义的推论。
In this paper, we report findings from a family-based association study examining the association between polymorphisms in two key estrogen-metabolism genes CYP1B1 (codon 432 G --> C and codon 453 A --> G variants) and COMT ( codon 158 G. A variant) and female breast cancer. We conducted the study among 280 nuclear families containing one or more daughters with breast cancer with a total of 1124 family members (702 with available constitutional DNA and questionnaire data and 421 without). These nuclear families were selected from breast cancer families participating in the Metropolitan New York Registry (MNYR)-one of the six centers of NCI's Breast Cooperative Family Registry. We used likelihood-based statistical methods to examine the allelic associations. We found none of the variant alleles of the CYP1B1 and COMT genes to be associated with breast cancer in these families. This was consistent with results from matched case-control analyses using all available sib-ships in these families. However, we found that parental carrier status of the CYP1B1 codon 453 variant G allele and the COMT codon 158 variant A allele was associated with breast cancer risk in daughters (independent of the daughters' own genotype). In conclusion, findings from this family-based study indicate that a woman's own CYP1B1 or COMT genotypes are not associated with her breast cancer risk. Although the study found that parental carrier status of certain CYP1B1 or COMT genotypes might be associated with daughter's breast cancer risk, the biological basis as well as independent confirmation of this finding need to be investigated in future larger family-based studies before making meaningful inferences.