SNPs in ultraconserved elements and familial breast cancer risk

被引:46
作者
Yang, Rongxi [1 ,2 ]
Frank, Bernd [1 ,2 ]
Hemminki, Kari [2 ,3 ]
Bartram, Claus R. [4 ]
Wappenschmidt, Barbara [5 ,6 ]
Sutter, Christian [4 ]
Kiechle, Marion [7 ]
Bugert, Peter [8 ]
Schmutzler, Rita K. [5 ,6 ]
Arnold, Norbert [9 ]
Weber, Bernhard H. F. [10 ]
Niederacher, Dieter [11 ]
Meindl, Alfons [7 ]
Burwinkel, Barbara [1 ,2 ]
机构
[1] Helmholtz Univ, Grp Mol Epidemiol, D-69120 Heidelberg, Germany
[2] German Canc Res Ctr, Div Mol Genet Epidemiol, D-69120 Heidelberg, Germany
[3] Karolinska Inst, Ctr Family & Community Med, D-69120 Heidelberg, Germany
[4] Univ Heidelberg, Inst Human Genet, D-69120 Heidelberg, Germany
[5] Univ Cologne, Dept Obstet & Gynaecol, Ctr Clin, Div Mol Gynaeco Oncol, D-50931 Cologne, Germany
[6] Univ Hosp Cologne, CMMC, D-50931 Cologne, Germany
[7] Tech Univ Munich, Klinikum Rechts Isar, Dept Obstet & Gynaecol, D-81675 Munich, Germany
[8] Univ Heidelberg, Inst Transfus Med & Immunol, Red Cross Blood Serv Baden Wurttemberg Hessen, Med Fac Mannheim, D-68167 Mannheim, Germany
[9] Univ Hosp Schleswig Holstein, Dept Obstet & Gynaecol, Div Oncol, D-24105 Kiel, Germany
[10] Univ Regensburg, Inst Human Genet, D-93053 Regensburg, Germany
[11] Univ Dusseldorf, Ctr Clin, Dept Obstet & Gynaecol, Div Mol Genet, D-40225 Dusseldorf, Germany
关键词
D O I
10.1093/carcin/bgm290
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Ultraconserved elements (UCEs) are segments of >200 bp length showing absolute sequence identity between orthologous regions of human, rat and mouse genomes. The selection factors acting on these UCEs are still unknown. Recent studies have shown that UCEs function as long-range enhancers of flanking genes or are involved in splicing when overlapping with exons. The depletion of UCEs among copy number variation as well as the significant under-representation of single-nucleotide polymorphisms (SNPs) within UCEs have also revealed their evolutional and functional importance indicating their potential impact on disease, such as cancer. In the present study, we investigated the influence of six SNPs within UCEs on familial breast cancer risk. Two out of six SNPs showed an association with familial breast cancer risk. Whereas rs9572903 showed only a borderline significant association, the frequency of the rare [G] allele of rs2056116 was higher in cases than in controls indicating an increased familial breast cancer risk ([G] versus [A]: odds ratio (OR) = 1.18, 95% confidence interval (CI) 1.06-1.30, P = 0.0020; [GG] versus [AA]: OR = 1.41, 95% CI 1.15-1.74, P = 0.0011). Interestingly, comparing with the older age group, the ORs were increased in woman younger than 50 years of age ([G] versus [A]: OR = 1.27, 95% CI 1.11-1.45, P = 0.0005; [GG] versus [AA]: OR = 1.60, 95% CI 1.22-2.10, P = 0.0007) pointing to an age- or hormone-related effect. This is the first study indicating that SNPs in UCEs might be associated with cancer risk.
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收藏
页码:351 / 355
页数:5
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