Meta-analysis of genome-wide association studies identifies common susceptibility polymorphisms for colorectal and endometrial cancer near SH2B3 and TSHZ1.
Meta-analysis of genome-wide association studies identifies common susceptibility polymorphisms for colorectal and endometrial cancer near SH2B3 and TSHZ1.
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DOI：
10.1038/srep17369
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发表时间：
2015-12-01
影响因子：
4.6
通讯作者：
Tomlinson I
中科院分区：
文献类型：
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作者：
Cheng TH;Thompson D;Painter J;O'Mara T;Gorman M;Martin L;Palles C;Jones A;Buchanan DD;Win AK;Hopper J;Jenkins M;Lindor NM;Newcomb PA;Gallinger S;Conti D;Schumacher F;Casey G;Giles GG;Pharoah P;Peto J;Cox A;Swerdlow A;Couch F;Cunningham JM;Goode EL;Winham SJ;Lambrechts D;Fasching P;Burwinkel B;Brenner H;Brauch H;Chang-Claude J;Salvesen HB;Kristensen V;Darabi H;Li J;Liu T;Lindblom A;Hall P;de Polanco ME;Sans M;Carracedo A;Castellvi-Bel S;Rojas-Martinez A;Aguiar Jnr S;Teixeira MR;Dunning AM;Dennis J;Otton G;Proietto T;Holliday E;Attia J;Ashton K;Scott RJ;McEvoy M;Dowdy SC;Fridley BL;Werner HM;Trovik J;Njolstad TS;Tham E;Mints M;Runnebaum I;Hillemanns P;Dörk T;Amant F;Schrauwen S;Hein A;Beckmann MW;Ekici A;Czene K;Meindl A;Bolla MK;Michailidou K;Tyrer JP;Wang Q;Ahmed S;Healey CS;Shah M;Annibali D;Depreeuw J;Al-Tassan NA;Harris R;Meyer BF;Whiffin N;Hosking FJ;Kinnersley B;Farrington SM;Timofeeva M;Tenesa A;Campbell H;Haile RW;Hodgson S;Carvajal-Carmona L;Cheadle JP;Easton D;Dunlop M;Houlston R;Spurdle A;Tomlinson I
几种基因的高风险突变易患结直肠癌（CRC）和子宫内膜癌（EC）。因此，我们假设，一些低风险的遗传变异也可能易患CRC和EC。使用CRC和EC全基因组关联系列，共13，265例癌症病例和40，245例对照，我们发现先前鉴定的CRC多态性rs 2736100（靠近TERT）的保护性等位基因[G]与EC风险相关（比值比（OR）= 1.08，P = 0.000167）;该多态性影响其他几种癌症的风险。TERC附近的进一步CRC多态性也显示与EC相关的证据（OR = 0.92; P = 0.03）。然而，总体而言，没有很好的证据表明CRC多态性与EC风险相关，并且先前报道的两种EC多态性均与CRC风险无关。联合分析显示，染色体12 q24上的一个全基因组显著多态性rs3184504（OR = 1.10，P = 7.23 × 10−9）对CRC和EC风险具有共同影响。这种多态性是SH 2B 3基因的错义变体，也与血液学和自身免疫性疾病有关，表明它通过免疫反应影响癌症风险。另一个多态性，靠近基因TSHZ 1的rs 12970291，与CRC和EC相关（OR = 1.26，P = 4.82 × 10−8），等位基因对两种癌症的风险表现出相反的影响。
High-risk mutations in several genes predispose to both colorectal cancer (CRC) and endometrial cancer (EC). We therefore hypothesised that some lower-risk genetic variants might also predispose to both CRC and EC. Using CRC and EC genome-wide association series, totalling 13,265 cancer cases and 40,245 controls, we found that the protective allele [G] at one previously-identified CRC polymorphism, rs2736100 near TERT, was associated with EC risk (odds ratio (OR) = 1.08, P = 0.000167); this polymorphism influences the risk of several other cancers. A further CRC polymorphism near TERC also showed evidence of association with EC (OR = 0.92; P = 0.03). Overall, however, there was no good evidence that the set of CRC polymorphisms was associated with EC risk, and neither of two previously-reported EC polymorphisms was associated with CRC risk. A combined analysis revealed one genome-wide significant polymorphism, rs3184504, on chromosome 12q24 (OR = 1.10, P = 7.23 × 10−9) with shared effects on CRC and EC risk. This polymorphism, a missense variant in the gene SH2B3, is also associated with haematological and autoimmune disorders, suggesting that it influences cancer risk through the immune response. Another polymorphism, rs12970291 near gene TSHZ1, was associated with both CRC and EC (OR = 1.26, P = 4.82 × 10−8), with the alleles showing opposite effects on the risks of the two cancers.