Breast cancer susceptibility risk associations and heterogeneity by E-cadherin tumor tissue expression.
Breast cancer susceptibility risk associations and heterogeneity by E-cadherin tumor tissue expression.
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DOI：
10.1007/s10549-013-2771-z
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发表时间：
2014-01
影响因子：
3.8
通讯作者：
Figueroa, Jonine D.
中科院分区：
文献类型：
--
作者：
Horne, Hisani N.;Sherman, Mark E.;Garcia-Closas, Montserrat;Pharoah, Paul D.;Blows, Fiona M.;Yang, Xiaohong R.;Hewitt, Stephen M.;Conway, Catherine M.;Lissowska, Jolanta;Brinton, Louise A.;Prokunina-Olsson, Ludmila;Dawson, Sarah-Jane;Caldas, Carlos;Easton, Douglas F.;Chanock, Stephen J.;Figueroa, Jonine D.
E-钙粘蛋白参与细胞-细胞粘附和上皮-间充质转化（EMT）。在癌症中，E-钙粘蛋白的丢失或失活与上皮细胞增殖和侵袭相关。在这里，我们试图确定在波兰乳腺癌研究（PBCS）中，18种乳腺癌易感性单核苷酸多态性（SNP）的风险关联是否与E-cadherin肿瘤组织表达不同，使用1，347例浸润性乳腺癌病例和2，366例对照的数据。使用肿瘤组织微阵列的免疫组织化学染色评估E-钙粘蛋白表达（低/高）。来自癌症遗传流行病学和危险因素研究（Study of Epidemiology and Risk Factors in Cancer Heredity，简称EADS）的2,006例病例和6,714例对照的重复数据被用于跟踪PBCS中有希望的发现。在PBCS中，我们发现1p11.2位点的rs 11249433 SNP与E-cadherin低水平肿瘤的风险（OR = 1.30，95%CI 1.08 - 1.56）比与E-cadherin高水平肿瘤（OR = 1.06，95%CI 0.95 - 1.18;仅病例p异质性（p-het）= 0.05）更强相关。PBCS中rs 11249433的结果在PIB中重复。对SNP rs 11249433的两个数据集的组合分析揭示了E-钙粘蛋白表达的显著异质性（仅组合病例p-het = 0.004）。此外，在rs 11249433携带者中，ER阳性和小叶组织学的E-cadherin低水平肿瘤的风险最高。我们在两个独立数据集的研究结果表明，rs 11249433，位于1p11.2基因座内的NOTCH 2和FCGR 1B基因之间，与E-cadherin表达低或缺乏的乳腺肿瘤的风险更密切相关，并表明E-cadherin肿瘤组织表达的评估可能有助于澄清乳腺癌风险因素的关联。
E-cadherin is involved in cell-cell adhesion and epithelial-to-mesenchymal transitions (EMT). In cancers, loss or inactivation of E-cadherin is associated with epithelial cell proliferation and invasion. Here, we sought to determine if risk associations for 18 breast cancer susceptibility single nucleotide polymorphisms (SNPs) differed by E-cadherin tumor tissue expression in the Polish Breast Cancer Study (PBCS), using data on 1,347 invasive breast cancer cases and 2,366 controls. E-cadherin expression (low/high) was assessed using immunohistochemical staining of tumor tissue microarrays. Replication data on 2,006 cases and 6,714 controls from the Study of Epidemiology and Risk Factors in Cancer Heredity (SEARCH) was used to follow-up promising findings from PBCS. In PBCS, we found the rs11249433 SNP at the 1p11.2 locus to be more strongly associated with risk of E-cadherin low tumors (OR = 1.30, 95% CI 1.08 – 1.56) than with E-cadherin high tumors (OR = 1.06, 95% CI 0.95 – 1.18; case-only p-heterogeneity (p-het) = 0.05). Findings in PBCS for rs11249433 were replicated in SEARCH. Combined analyses of the two datasets for SNP rs11249433 revealed significant heterogeneity by E-cadherin expression (combined case-only p-het = 0.004). Further, among carriers of rs11249433, the highest risk was seen for E-cadherin low tumors that were ER-positive and of lobular histology. Our results in two independent data sets suggest that rs11249433, which is located between the NOTCH2 and FCGR1B genes within the 1p11.2 locus, is more strongly associated with risk of breast tumors with low or absent E-cadherin expression, and suggest that evaluation of E-cadherin tumor tissue expression may be useful in clarifying breast cancer risk factor associations.
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影响因子：
14.9
作者：
Ward LD;Kellis M
通讯作者：
Kellis M
影响因子：
23.9
作者：
Bouras, Toula;Pal, Bhupinder;Visvader, Jane E.
通讯作者：
Visvader, Jane E.
影响因子：
3.8
作者：
Yang, Xiaohong R.;Sherman, Mark E.;Garcia-Closas, Montserrat
通讯作者：
Garcia-Closas, Montserrat
影响因子：
10.5
作者：
Timmerman, LA;Grego-Bessa, J;de la Pompa, JL
通讯作者：
de la Pompa, JL
影响因子：
5.7
作者：
Szasz, Attila M.;Nemeth, Zsuzsanna;Kulka, Janina
通讯作者：
Kulka, Janina