美国西储大学（Case Western Reserve University）医学院的科学家在3月7日的《美国人类遗传学杂志》（AJHG）上发表论文称，他们识别出了结直肠癌（CRC）的遗传成分。该研究是美国进行的第一个关于CRC患病家族和结肠息肉之间联系的大型课题，它基于此前的一项研究——认为染色体9q的一个特别区域可能隐藏着CRC易感基因。经过对194个家族的全部染色体对的全基因组扫描，研究人员额外在染色体1p、15q和17p处识别出了CRC的基因区域。
在研究中，研究人员在对患结肠癌和结肠息肉的家族进行研究同时，还对同时患有其他种类癌症（如多发性息肉和乳腺癌）的家族进行了分析。这些不同的显型表现出与不同染色体区域的联系，研究人员认为这支持了多种易感性基因导致不同种类癌症的观点。这些联系将在下一阶段研究中进行深入的分析。
领导这项研究的医学博士Georgia L. Wiesner说：“这项研究的目的是识别出易患病人群体内的CRC基因，从而了解哪些人容易患病和为什么。这项成果向遗传检测CRC迈出了重要的一步。”
最新研究中使用的全基因组扫描将在未来帮助医生们解释CRC的遗传要素。一旦识别出这些基因，医生们就能够利用这些遗传标记识别出“有危险”的病人，然后在标准检查年龄（50岁）之前对这些病人更好地进行如结肠镜检查等癌症监控。
由于目前没有基因测试，家族病史是唯一判断病人患CRC风险的依据。明确知道CRC的基因将使医生能够更好地照顾CRC病人并能实现早期监控。（科学网 刘乐/编译）
生物谷推荐原始出处：
（The American Journal of Human Genetics），doi:10.1016/j.ajhg.2008.01.007，Denise Daley, Georgia L. Wiesner
Identification of Susceptibility Genes for Cancer in a Genome-wide Scan: Results from the Colon Neoplasia Sibling Study
Denise Daley1, 9, , , Susan Lewis2, Petra Platzer3, 8, Melissa MacMillen3, Joseph Willis5, Robert C. Elston1, 6, Sanford D. Markowitz4, 6, 8 and Georgia L. Wiesner3, 4, 6, 7
1Departments of Epidemiology and Biostatistics, University Hospitals of Cleveland/Case Western Reserve University, Cleveland, OH 44106, USA
2Department of Genetics, University Hospitals of Cleveland/Case Western Reserve University, Cleveland, OH 44106, USA
3Department of Medicine, University Hospitals of Cleveland/Case Western Reserve University, Cleveland, OH 44106, USA
4Department of Pathology, University Hospitals of Cleveland/Case Western Reserve University, Cleveland, OH 44106, USA
5Case Comprehensive Cancer Center, University Hospitals of Cleveland/Case Western Reserve University, Cleveland, OH 44106, USA
6Center for Human Genetics, University Hospitals of Cleveland/Case Western Reserve University, Cleveland, OH 44106, USA
7Howard Hughes Medical Institute, Cleveland, OH 44195, USA
8Genomic Medicine Institute Cleveland Clinic Foundation, Cleveland, OH 44195, USA
9University of British Columbia, Vancouver, BC V6T 1Z4, Canada
Received 14 August 2007; revised 10 December 2007; accepted 7 January 2008. Published online: February 28, 2008. Available online 28 February 2008.
Colorectal cancer (CRC) is the third most commonly diagnosed cancer in Americans and is the second leading cause of cancer mortality. Only a minority (5%) of familial CRC can be explained by known genetic variants. To identify susceptibility genes for familial colorectal neoplasia, the colon neoplasia sibling study conducted a comprehensive, genome-wide linkage scan of 194 kindreds. Clinical information (histopathology, size and number of polyps, and other primary cancers) was used in conjunction with age at onset and family history for classification of the families into five phenotypic subgroups (severe histopathology, oligopolyposis, young, colon/breast, and multiple cancer) prior to analysis. By expanding the traditional affected-sib-pair design to include unaffected and discordant sib pairs, analytical power and robustness to type I error were increased. Sib-pair linkage statistics and Haseman-Elston regression identified 19 linkage peaks, with interesting results for chromosomes 1p31.1, 15q14-q22, 17p13.3, and 21. At marker D1S1665 (1p31.1), there was strong evidence for linkage in the multiple-cancer subgroup (p = 0.00007). For chromosome 15q14-q22, a linkage peak was identified in the full-sample (p = 0.018), oligopolyposis (p = 0.003), and young (p = 0.0009) phenotypes. This region includes the HMPS/CRAC1 locus associated with hereditary mixed polyposis syndrome (HMPS) in families of Ashkenazi descent. We provide compelling evidence linking this region in families of European descent with oligopolyposis and/or young age at onset (≤51) phenotypes. We found linkage to BRCA2 in the colon/breast phenotypic subgroup and identified a second locus in the region of D21S1437 segregating with, but distinct from, BRCA2. Linkage to 17p13.3 at marker D17S1308 in the breast/colon subgroup identified HIC1 as a candidate gene. We demonstrated that using clinical information, unaffected siblings, and family history can increase the analytical power of a linkage study.
