Associations between polymorphisms in glucuronidation and sulfation enzymes and mammographic breast density in premenopausal women in the United States.
Associations between polymorphisms in glucuronidation and sulfation enzymes and mammographic breast density in premenopausal women in the United States.
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DOI：
10.1158/1055-9965.epi-09-0898
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发表时间：
2010-02
期刊：
影响因子：
--
通讯作者：
Lampe JW
中科院分区：
文献类型：
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作者：
Yong M;Schwartz SM;Atkinson C;Makar KW;Thomas SS;Newton KM;Aiello Bowles EJ;Holt VL;Leisenring WM;Lampe JW
性激素通过（i）UDP-葡萄糖醛酸转移酶（UGT）催化的葡萄糖醛酸化和（ii）磺基转移酶（SULT）催化的硫酸化代谢为活性较低的化合物。功能性UGT和SULT多态性可影响性激素的清除，从而影响对性激素敏感的组织（如乳腺）的暴露。我们评估了绝经前妇女UGT和SULT基因功能多态性与乳腺密度之间的关系。175名年龄在40-45岁之间的妇女，在前一年进行了筛查性乳房X光检查，提供了基因组DNA样本。将乳房X线照片数字化以获得乳房密度测量值。使用广义线性回归，我们评估了乳腺密度百分比与UGT 1A和UGT 2B家族、SULT 1A 1和SULT 1 E1多态性之间的关联。在控制种族后，与SULT 1A 1（R213/R213）基因型的女性相比，SULT 1A 1（H213/H213）基因型的女性乳腺密度降低了16%（p值= 0.001）。与UGT 1A 1（TA 6）-UG 1A 3（W11）-UGT 1A 3（V47）单倍型相比，携带至少一个拷贝的UGT 1A 1（TA 7）-UG 1A 3（R11）-UGT 1A 3（A47）单倍型的女性乳腺密度低5%（p值= 0.07）。未观察到UGT 2B家族或SULT 1 E1多态性与乳腺密度之间的关联。SULT 1A 1和UGT 1A基因座的多态性可能影响绝经前妇女的乳腺密度百分比。
Sex hormones are metabolized to less active compounds via (i) glucuronidation, catalyzed by UDP-glucuronosyltransferases (UGT) and (ii) sulfation, catalyzed by sulfotransferases (SULT). Functional UGT and SULT polymorphisms can affect clearance of sex hormones, thereby influencing exposure in hormone-sensitive tissues, such as the breast. We assessed relationships between functional polymorphisms in the UGT and SULT genes and breast density in premenopausal women. One-hundred and seventy five women ages 40–45 years, who had a screening mammogram taken within the previous year, provided a genomic DNA sample. Mammograms were digitized to obtain breast density measures. Using generalized linear regression, we assessed associations between percent breast density and polymorphisms in the UGT1A and UGT2B families, SULT1A1, and SULT1E1. Women with the SULT1A1(H213/H213) genotype had 16% lower percent breast density compared to women with the SULT1A1(R213/R213) genotype after controlling for ethnicity (p-value = 0.001). Breast density was 5% lower among women carrying at least one copy of the UGT1A1(TA7)-UG1A3(R11)-UGT1A3(A47) haplotype compared to the UGT1A1(TA6)-UG1A3(W11)-UGT1A3(V47) haplotype (p-value = 0.07). No associations were observed between polymorphisms in the UGT2B family or SULT1E1 and breast density. Polymorphisms in SULT1A1 and the UGT1A locus may influence percent breast density in premenopausal women.