美國西儲大學（Case Western Reserve University）醫(yī)學院的科學家在3月7日的《美國人類遺傳學雜志》（AJHG）上發(fā)表論文稱,，他們識別出了結(jié)直腸癌（CRC）的遺傳成分。該研究是美國進行的第一個關于CRC患病家族和結(jié)腸息肉之間聯(lián)系的大型課題,，它基于此前的一項研究——認為染色體9q的一個特別區(qū)域可能隱藏著CRC易感基因。經(jīng)過對194個家族的全部染色體對的全基因組掃描,，研究人員額外在染色體1p,、15q和17p處識別出了CRC的基因區(qū)域。
在研究中,，研究人員在對患結(jié)腸癌和結(jié)腸息肉的家族進行研究同時,，還對同時患有其他種類癌癥（如多發(fā)性息肉和乳腺癌）的家族進行了分析。這些不同的顯型表現(xiàn)出與不同染色體區(qū)域的聯(lián)系,，研究人員認為這支持了多種易感性基因?qū)е虏煌N類癌癥的觀點,。這些聯(lián)系將在下一階段研究中進行深入的分析。
領導這項研究的醫(yī)學博士Georgia L. Wiesner說：“這項研究的目的是識別出易患病人群體內(nèi)的CRC基因,，從而了解哪些人容易患病和為什么,。這項成果向遺傳檢測CRC邁出了重要的一步。”
最新研究中使用的全基因組掃描將在未來幫助醫(yī)生們解釋CRC的遺傳要素,。一旦識別出這些基因,，醫(yī)生們就能夠利用這些遺傳標記識別出“有危險”的病人，然后在標準檢查年齡（50歲）之前對這些病人更好地進行如結(jié)腸鏡檢查等癌癥監(jiān)控,。
由于目前沒有基因測試,，家族病史是唯一判斷病人患CRC風險的依據(jù)。明確知道CRC的基因?qū)⑹贯t(yī)生能夠更好地照顧CRC病人并能實現(xiàn)早期監(jiān)控,。（科學網(wǎng) 劉樂/編譯）
生物谷推薦原始出處：
（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.
