图片说明:如果能够及早发现,结直肠癌比较容易治疗。
(图片来源:Punchstock)
英国科学家近日发现一种特殊的基因变异,它能够使白种人患结肠癌(世界第三大癌症形式)的风险增加10%,而对日本人却毫无影响。这是首个具种族特异性的与结肠癌易感性有关的基因变异,有望帮助人们开展特定种族的结直肠癌风险评估,以便做到早发现早治疗。相关论文3月30日在线发表于《自然—遗传学》(Nature Genetics)上。
领导此次研究的是英国爱丁堡大学的Malcolm Dunlop。研究人员从1000多个苏格兰癌症病人身上采集DNA样本,筛选与癌症有关的基因变异。随后,他们在另外几千个病人身上重复这一过程,并与来自其它种族的样本进行比较。结果在基因组中发现了三个与结直肠癌存在明确关联的变异,其中一个位于11号染色体上的变异能够增加苏格兰人的结肠癌易感性,而对日本人却没有影响。
Dunlop表示,这种种族间差别的存在原因目前尚不清楚,或许可以归因于种族间其它未知的遗传差异,或是饮食等生活方式的差别。
令人感兴趣的是,这一基因变异只在影响结肠癌风险方面具有种族特异性。研究发现,带有这一变异的白种人和日本人在患直肠癌的风险方面大略相当,表明这一变异的作用精细而具有特异性。
在3月30日在线发表的另一项类似研究中,由英国萨顿癌症研究所的Richard Houlston领导的研究小组发现了另外两个与结直肠癌有关的基因变异。Dunlop说,带有全部这几个变异的人患结直肠癌的风险是不带这些变异人的4到5倍。
英国目前已经开始一个全国性的结直肠癌排查项目。Dunlop认为,在患病前就检测出危险基因对公众来说具有重要的意义,它将允许人们“修剪”自己的生活方式以尽力避免患上肠道癌症。
他同时表示,虽然还需要一定的时间,但具种族特异性的、甚至是个体化的癌症易感性测试必将成为现实。(科学网 梅进/编译)
生物谷推荐原始出处:
(Nature Genetics),doi:10.1038/ng.133,Albert Tenesa,Malcolm G Dunlop
Genome-wide association scan identifies a colorectal cancer susceptibility locus on 11q23 and replicates risk loci at 8q24 and 18q21
Albert Tenesa1,31, Susan M Farrington1,31, James G D Prendergast1, Mary E Porteous2, Marion Walker1, Naila Haq1, Rebecca A Barnetson1, Evropi Theodoratou1,3, Roseanne Cetnarskyj2, Nicola Cartwright1, Colin Semple1, Andrew J Clark1, Fiona J L Reid4, Lorna A Smith4, Kostas Kavoussanakis4, Thibaud Koessler5, Paul D P Pharoah5, Stephan Buch6,7, Clemens Schafmayer7,8, Jürgen Tepel6,8, Stefan Schreiber7,9, Henry Völzke10, Carsten O Schmidt10, Jochen Hampe6, Jenny Chang-Claude11, Michael Hoffmeister12, Hermann Brenner12, Stefan Wilkening13, Federico Canzian13, Gabriel Capella14, Victor Moreno15, Ian J Deary16, John M Starr17, Ian P M Tomlinson18, Zoe Kemp18, Luis Carvajal-Carmona18, Emily Webb19, Peter Broderick19, Jayaram Vijayakrishnan19, Richard S Houlston19, Gad Rennert20, Dennis Ballinger21, Laura Rozek22, Stephen B Gruber22, Koichi Matsuda23, Tomohide Kidokoro23, Yusuke Nakamura23, Brent W Zanke24,25,26, Celia M T Greenwood24,27,28, Jagadish Rangrej18,27, Rafal Kustra24, Alexandre Montpetit29, Thomas J Hudson24,25, Steven Gallinger24,30, Harry Campbell1,3 & Malcolm G Dunlop1
In a genome-wide association study to identify loci associated with colorectal cancer (CRC) risk, we genotyped 555,510 SNPs in 1,012 early-onset Scottish CRC cases and 1,012 controls (phase 1). In phase 2, we genotyped the 15,008 highest-ranked SNPs in 2,057 Scottish cases and 2,111 controls. We then genotyped the five highest-ranked SNPs from the joint phase 1 and 2 analysis in 14,500 cases and 13,294 controls from seven populations, and identified a previously unreported association, rs3802842 on 11q23 (OR = 1.1; P = 5.8 10-10), showing population differences in risk. We also replicated and fine-mapped associations at 8q24 (rs7014346; OR = 1.19; P = 8.6 10-26) and 18q21 (rs4939827; OR = 1.2; P = 7.8 10-28). Risk was greater for rectal than for colon cancer for rs3802842 (P < 0.008) and rs4939827 (P < 0.009). Carrying all six possible risk alleles yielded OR = 2.6 (95% CI = 1.75–3.89) for CRC. These findings extend our understanding of the role of common genetic variation in CRC etiology.
(Nature Genetics),doi:10.1038/ng.111,Ian PM Tomlinson,Richard S Houlston
A genome-wide association study identifies colorectal cancer susceptibility loci on chromosomes 10p14 and 8q23.3
Ian PM Tomlinson1,38, Emily Webb2, Luis Carvajal-Carmona1, Peter Broderick2, Kimberley Howarth1, Alan M Pittman2, Sarah Spain1, Steven Lubbe2, Axel Walther1, Kate Sullivan2, Emma Jaeger1, Sarah Fielding2, Andrew Rowan1, Jayaram Vijayakrishnan2, Enric Domingo1, Ian Chandler2, Zoe Kemp1, Mobshra Qureshi2, Susan M Farrington3, Albert Tenesa3, James GD Prendergast3, Rebecca A Barnetson3, Steven Penegar2, Ella Barclay1, Wendy Wood2, Lynn Martin1,4,5, Maggie Gorman1, Huw Thomas6, Julian Peto7,8, D Timothy Bishop9, Richard Gray10, Eamonn R Maher5, Anneke Lucassen11, David Kerr12, D Gareth R Evans4, The CORGI Consortium37, Clemens Schafmayer13,14, Stephan Buch16,17, Henry Völzke15, Jochen Hampe16, Stefan Schreiber14,17, Ulrich John15, Thibaud Koessler18, Paul Pharoah18, Tom van Wezel19, Hans Morreau19, Juul T Wijnen20, John L Hopper21, Melissa C Southey22, Graham G Giles21,23, Gianluca Severi23, Sergi Castellví-Bel24, Clara Ruiz-Ponte25, Angel Carracedo25, Antoni Castells24, The EPICOLON Consortium37, Asta Försti26,27, Kari Hemminki26,27, Pavel Vodicka28, Alessio Naccarati28, Lara Lipton29, Judy WC Ho30, K K Cheng30, Pak C Sham30, J Luk30, Jose AG Agúndez31, Jose M Ladero32, Miguel de la Hoya33, Trinidad Caldés33, Iina Niittymäki34, Sari Tuupanene34, Auli Karhu34, Lauri Aaltonen34, Jean-Baptiste Cazier35, Harry Campbell36,38, Malcolm G Dunlop3,38 & Richard S Houlston2,38
To identify colorectal cancer (CRC) susceptibility alleles, we conducted a genome-wide association study. In phase 1, we genotyped 550,163 tagSNPs in 940 familial colorectal tumor cases (627 CRC, 313 high-risk adenoma) and 965 controls. In phase 2, we genotyped 42,708 selected SNPs in 2,873 CRC cases and 2,871 controls. In phase 3, we evaluated 11 SNPs showing association at P < 10-4 in a joint analysis of phases 1 and 2 in 4,287 CRC cases and 3,743 controls. Two SNPs were taken forward to phase 4 genotyping (10,731 CRC cases and 10,961 controls from eight centers). In addition to the previously reported 8q24, 15q13 and 18q21 CRC risk loci, we identified two previously unreported associations: rs10795668, located at 10p14 (P = 2.5 10-13 overall; P = 6.9 10-12 replication), and rs16892766, at 8q23.3 (P = 3.3 10-18 overall; P = 9.6 10-17 replication), which tags a plausible causative gene, EIF3H. These data provide further evidence for the 'common-disease common-variant' model of CRC predisposition.