Association of single nucleotide polymorphisms in Wnt signaling pathway genes with breast cancer in Saudi patients.
Association of single nucleotide polymorphisms in Wnt signaling pathway genes with breast cancer in Saudi patients.
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DOI：
10.1371/journal.pone.0059555
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Khan Z
中科院分区：
文献类型：
--
作者：
Alanazi MS;Parine NR;Shaik JP;Alabdulkarim HA;Ajaj SA;Khan Z
乳腺癌是一种复杂的异质性疾病，涉及编码蛋白质的基因的遗传和表观遗传改变，这些蛋白质是各种信号通路的组分。候选基因方法已经确定了Wnt信号通路基因中的遗传变异与包括乳腺癌在内的几种疾病易感性增加的相关性。由于Wnt通路关键基因的体细胞突变的罕见性，我们研究了这些基因中的遗传变异与乳腺癌易感性的关联。我们进行了一项病例对照研究，通过检查位于与Wnt信号相关的8个基因中的15个SNP来识别风险变异。单个位点的基因型分析显示，位于β-catenin、AXIN 2、DKK 3、SFRP 3和TCF 7 L2的5个SNP与乳腺癌有统计学显著相关。仅在β-catenin的SNP中观察到风险增加，而其他四种SNP则提供了对乳腺癌的保护。在基于雌激素受体状态和乳腺癌发病年龄对病例进行分层后，大多数相关性仍然存在。编码精氨酸或甘氨酸的SFRP 3基因外显子6中的rs7775 SNP与乳腺癌表现出非常强的相关性，即使在Bonferroni校正后。除了这五种变异，AXIN 2中的rs3923086和DKK 4中的rs3763511在总体人群中没有显示出任何相关性，分别与早发性和雌激素受体阴性乳腺癌显著相关。这是第一项利用基于途径的方法来确定Wnt信号通路基因中风险变体与乳腺癌的关联的研究。在不同种族的更大人群中证实我们的发现将为Wnt通路的作用以及乳腺癌早期检测的筛选标志物提供证据。
Breast cancer is a complex heterogeneous disease involving genetic and epigenetic alterations in genes encoding proteins that are components of various signaling pathways. Candidate gene approach have identified association of genetic variants in the Wnt signaling pathway genes and increased susceptibility to several diseases including breast cancer. Due to the rarity of somatic mutations in key genes of Wnt pathway, we investigated the association of genetic variants in these genes with predisposition to breast cancers. We performed a case-control study to identify risk variants by examining 15 SNPs located in 8 genes associated with Wnt signaling. Genotypic analysis of individual locus showed statistically significant association of five SNPs located in β-catenin, AXIN2, DKK3, SFRP3 and TCF7L2 with breast cancers. Increased risk was observed only with the SNP in β-catenin while the other four SNPs conferred protection against breast cancers. Majority of these associations persisted after stratification of the cases based on estrogen receptor status and age of on-set of breast cancer. The rs7775 SNP in exon 6 of SFRP3 gene that codes for either arginine or glycine exhibited very strong association with breast cancer, even after Bonferroni's correction. Apart from these five variants, rs3923086 in AXIN2 and rs3763511 in DKK4 that did not show any association in the overall population were significantly associated with early on-set and estrogen receptor negative breast cancers, respectively. This is the first study to utilize pathway based approach to identify association of risk variants in the Wnt signaling pathway genes with breast cancers. Confirmation of our findings in larger populations of different ethnicities would provide evidence for the role of Wnt pathway as well as screening markers for early detection of breast carcinomas.
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影响因子：
56.9
作者：
Behrens, J;Jerchow, BA;Birchmeier, W
通讯作者：
Birchmeier, W
影响因子：
3.8
作者：
Anderson, William F.;Chen, Bingshu E.;Rosenberg, Philip S.
通讯作者：
Rosenberg, Philip S.
影响因子：
64.8
作者：
Curtis, Christina;Shah, Sohrab P.;Chin, Suet-Feung;Turashvili, Gulisa;Rueda, Oscar M.;Dunning, Mark J.;Speed, Doug;Lynch, Andy G.;Samarajiwa, Shamith;Yuan, Yinyin;Graef, Stefan;Ha, Gavin;Haffari, Gholamreza;Bashashati, Ali;Russell, Roslin;McKinney, Steven;Langerod, Anita;Green, Andrew;Provenzano, Elena;Wishart, Gordon;Pinder, Sarah;Watson, Peter;Markowetz, Florian;Murphy, Leigh;Ellis, Ian;Purushotham, Arnie;Borresen-Dale, Anne-Lise;Brenton, James D.;Tavare, Simon;Caldas, Carlos;Aparicio, Samuel
通讯作者：
Aparicio, Samuel
Wnt途径基因的遗传变化是乳房化生癌中的常见事件。
DOI：
10.1158/1078-0432.ccr-07-4379
发表时间：
2008-07-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Hayes MJ;Thomas D;Emmons A;Giordano TJ;Kleer CG
通讯作者：
Kleer CG
影响因子：
30.8
作者：
Grant, SFA;Thorleifsson, G;Stefansson, K
通讯作者：
Stefansson, K