基因SMAD7的普通變異會(huì)增加直腸癌發(fā)生的風(fēng)險(xiǎn),，這一最新的研究成果在線(xiàn)發(fā)表在10月號(hào)的《自然—遺傳學(xué)》期刊上,。
Richard Houlston和Ian Tomlinson與同事合作進(jìn)行了一次泛基因相關(guān)性研究,，對(duì)幾千位有家族直腸癌史的個(gè)體和對(duì)照組進(jìn)行研究,，測(cè)試了50多萬(wàn)個(gè)單核苷酸多態(tài)性（SNPs）的基因型,。最初的樣品分析顯示，基因SMAD7中的3個(gè)SNPs與直腸癌風(fēng)險(xiǎn)的增加有關(guān),。
基因SMAD7是一種細(xì)胞內(nèi)分子，它能抑制TGF-β通道,，在多種組織中，TGF-β與細(xì)胞間的信號(hào)傳遞有關(guān),。盡管SMAD7中的變異對(duì)直腸癌風(fēng)險(xiǎn)的增加影響不大,，但對(duì)普通人群而言,，它會(huì)增加15%的直腸癌發(fā)生風(fēng)險(xiǎn),，比家族性風(fēng)險(xiǎn)因子小1%。結(jié)合最新的數(shù)據(jù),，這些普通變異的效應(yīng)在這種疾病中確實(shí)存在，而且能夠被發(fā)現(xiàn),。(科學(xué)時(shí)報(bào))
原始出處:
Nature Genetics 39, 1315 - 1317 (2007)
Published online: 14 October 2007 | doi:10.1038/ng.2007.18
A genome-wide association study shows that common alleles of SMAD7 influence colorectal cancer risk
Peter Broderick1,14, Luis Carvajal-Carmona2,3,14, Alan M Pittman1,14, Emily Webb1,14, Kimberley Howarth2, Andrew Rowan2, Steven Lubbe1, Sarah Spain2, Kate Sullivan1, Sarah Fielding1, Emma Jaeger2, Jayaram Vijayakrishnan1, Zoe Kemp2, Maggie Gorman2, Ian Chandler1, Elli Papaemmanuil1, Steven Penegar1, Wendy Wood1, Gabrielle Sellick1, Mobshra Qureshi1, Ana Teixeira2, Enric Domingo2, Ella Barclay2, Lynn Martin2,4,5, Oliver Sieber6, members of the CORGI Consortium, David Kerr7, Richard Gray8, Julian Peto9,10,11, Jean-Baptiste Cazier12, Ian Tomlinson2,3 & Richard S Houlston1
To identify risk variants for colorectal cancer (CRC), we conducted a genome-wide association study, genotyping 550,163 tag SNPs in 940 individuals with familial colorectal tumor (627 CRC, 313 advanced adenomas) and 965 controls. We evaluated selected SNPs in three replication sample sets (7,473 cases, 5,984 controls) and identified three SNPs in SMAD7 (involved in TGF- and Wnt signaling) associated with CRC. Across the four sample sets, the association between rs4939827 and CRC was highly statistically significant (Ptrend = 1.0 10-12).
Section of Cancer Genetics, Institute of Cancer Research, Sutton SM2 5NG, UK.
Molecular and Population Genetics Laboratory, London Research Institute, Cancer Research UK, London WC2A 3PX, UK.
Institute of Cancer, Bart's and the London Medical School, Queen Mary College, University of London, London EC1M 6BQ, UK.
Department of Medical Genetics, St Mary's Hospital, Manchester M13 OJH, UK.
Department of Medical Genetics, Birmingham Women's Hospital, Edgbaston, Birmingham B15 2TG, UK.
Cancer and Immunogenetics Laboratory, Weatherall Institute for Molecular Medicine, Oxford University, Oxford OX3 9DS, UK.
Department of Clinical Pharmacology, Oxford University, Radcliffe Infirmary, Oxford OX2 6HA, UK.
Birmingham Clinical Trials Unit, University of Birmingham, Birmingham B15 2TT, UK.
The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London SW3 6JB, UK.
Non-Communicable Disease Epidemiology Unit, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.
Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
Bioinformatics and Biostatistics, London Research Institute, Cancer Research UK, London WC2A 3PX, UK.
A full list of authors is provided in the Supplementary Note online.
These authors contributed equally to this work.
Correspondence to: Richard S Houlston1 e-mail: [email protected]
Correspondence to: Ian Tomlinson2,3 e-mail: [email protected]
