基因SMAD7的普通变异会增加直肠癌发生的风险，这一最新的研究成果在线发表在10月号的《自然—遗传学》期刊上。
Richard Houlston和Ian Tomlinson与同事合作进行了一次泛基因相关性研究，对几千位有家族直肠癌史的个体和对照组进行研究，测试了50多万个单核苷酸多态性（SNPs）的基因型。最初的样品分析显示，基因SMAD7中的3个SNPs与直肠癌风险的增加有关。
基因SMAD7是一种细胞内分子，它能抑制TGF-β通道，在多种组织中，TGF-β与细胞间的信号传递有关。尽管SMAD7中的变异对直肠癌风险的增加影响不大，但对普通人群而言，它会增加15%的直肠癌发生风险，比家族性风险因子小1%。结合最新的数据，这些普通变异的效应在这种疾病中确实存在，而且能够被发现。(科学时报)
原始出处:
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: richard.houlston@icr.ac.uk
Correspondence to: Ian Tomlinson2,3 e-mail: ian.tomlinson@cancer.org.uk
