Polymorphisms in the carcinogen detoxification genes CYB5A and CYB5R3 and breast cancer risk in African American women.
Polymorphisms in the carcinogen detoxification genes CYB5A and CYB5R3 and breast cancer risk in African American women.
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DOI：
10.1007/s10552-014-0454-7
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发表时间：
2014-11
期刊：
影响因子：
--
通讯作者：
Trepanier LA
中科院分区：
文献类型：
--
作者：
Blanke KL;Sacco JC;Millikan RC;Olshan AF;Luo J;Trepanier LA
细胞色素 b5（由 CYB5A 编码）和 NADH 细胞色素 b5 还原酶（由 CYB5R3 编码）可解毒香烟烟雾中发现的芳香族和杂环胺乳腺癌致癌物。我们假设 CYB5A 和 CYB5R3 多态性与女性乳腺癌风险相关。我们对卡罗莱纳州乳腺癌研究人群（1946 例病例和 1747 例对照）中非裔美国人 (AfrAm) 和白种人 (Cauc) 女性的基因组 DNA 中 18 种 CYB5A 和 CYB5R3 变异的患病率进行了表征，并确定了它们与乳腺癌风险的关联，并通过吸烟改变了效应。与对照组相比，CYB5R3 变体 I1M+6T (rs8190370) 在乳腺癌病例 (MAF 0.0238) 中显着更常见 (0.0169，P = 0.039)；这是由于与 AfrAm 对照组 (0.0441，P=0.046；调整后 OR 1.41，CI 0.98-2.04；P=0.062) 相比，AfrAm 病例 (0.0611) 的 MAF 较高。当考虑吸烟时，与从不吸烟者相比（OR=1.21；0.77-1.88；交互作用 P=0.176），AfrAm 吸烟者的 I1M+6T 与乳腺癌风险的相关性更强（调整后 OR 2.10、1.08-4.07；P=0.028）。与 Caucs 相比，I1M+6T 和另外三个 CYB5R3 变体 -251T、I8-1676C 和 *392C，以及两个 CYB5A 变体 13G 和 I2-992T 在 AfrAms 中明显更常见。在未来非洲裔乳腺癌风险的分子流行病学研究中应考虑 CYB5R3 I1M+6 C>T。此外，在评估 AfrAms 中与芳香族和杂环胺暴露相关的其他肿瘤时，应考虑 CYB5A 和 CYB5R3 的变异，包括前列腺癌、膀胱癌和结肠癌。
Cytochrome b5 (encoded by CYB5A) and NADH cytochrome b5 reductase (encoded by CYB5R3) detoxify aromatic and heterocyclic amine mammary carcinogens found in cigarette smoke. We hypothesized that CYB5A and CYB5R3 polymorphisms would be associated with breast cancer risk in women. We characterized the prevalence of 18 CYB5A and CYB5R3 variants in genomic DNA from African American (AfrAm) and Caucasian (Cauc) women from the Carolina Breast Cancer Study population (1946 cases and 1747 controls), and determined their associations with breast cancer risk, with effect modification by smoking. A CYB5R3 variant, I1M+6T (rs8190370) was significantly more common in breast cancer cases (MAF 0.0238) compared to controls (0.0169, P =0.039); this was attributable to a higher MAF in AfrAm cases (0.0611) compared to AfrAm controls (0.0441, P=0.046; adjusted OR 1.41, CI 0.98-2.04; P=0.062). When smoking was considered, I1M+6T was more strongly associated with breast cancer risk in AfrAm smokers (adjusted OR 2.10, 1.08-4.07; P=0.028) compared to never-smokers (OR=1.21; 0.77-1.88; P for interaction=0.176). I1M+6T and three additional CYB5R3 variants, -251T, I8-1676C, and *392C, as well as two CYB5A variants, 13G and I2-992T, were significantly more common in AfrAms compared to Caucs. CYB5R3 I1M+6 C>T should be considered in future molecular epidemiologic studies of breast cancer risk in AfrAms. Further, variants in CYB5A and CYB5R3 should be considered in the evaluation of other tumors in AfrAms that are associated with aromatic and heterocyclic amine exposures, to include prostate, bladder, and colon cancers.
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DOI：
10.1038/newbio229252a0
发表时间：
1971-01-01
期刊：
NATURE-NEW BIOLOGY
影响因子：
--
作者：
HULTQUIST, DE;PASSON, PG
通讯作者：
PASSON, PG
影响因子：
14.9
作者：
Grillo G;Turi A;Licciulli F;Mignone F;Liuni S;Banfi S;Gennarino VA;Horner DS;Pavesi G;Picardi E;Pesole G
通讯作者：
Pesole G
影响因子：
--
作者：
BROWNSON, RC;BLACKWELL, CW;PAPERMASTER, BW
通讯作者：
PAPERMASTER, BW
影响因子：
158.5
作者：
HEGESH, E;HEGESH, J;KAFTORY, A
通讯作者：
KAFTORY, A
影响因子：
2.8
作者：
Hecht, SS
通讯作者：
Hecht, SS