2008年1月的爱思唯尔期刊《临床肠胃病学与肝脏病学》（Clinical Gastroenterology and Hepatology）刊登了美国犹他州大学亨斯迈癌症研究所（Huntsman Cancer Institute）关于探寻现今美国结肠癌病源头的研究。科学家发现了一种原始的基因突变，很多现今的人群中的基因突变都可以追溯与此。
研究人员研究了犹他州和纽约州携带有一种高几率患结直肠癌的基因突变两个家族。研究发现这两个家族竟然有着共同的祖先。研究人员认为，这同时也意味着会有更多的美国家庭携带着这个基因，此外这个基因突变可能与许多美国现今结肠癌的病例都有一定关联。该基因突变会引起一种名为衰减家族性腺瘤性息肉病(AFAP)的疾病。在没有适当的临床护理下，携有AFAP突变的人群在80岁时会有非常高的几率患结肠癌，平均每3个人中就会有两个患病，远远高于正常的每24个人会有1个人患病的几率。
研究人员认为，患者应该知道自己的家族病史并尽早采取措施就可以有效地避免。癌前息肉经常会在突变携带者20岁后诊断出，结肠癌也已能在20多岁时候确诊。但是研究人员解释，临床诊断出AFAP却很困难，因为结肠癌的病发一般在50多岁左右，同时也具有偶发性的和非遗传性。研究人员认为人们有必要跟他们的家人了解他们家庭癌症史，并将此告知他们的医生。医生应该对AFAP有清醒的认识 ，对患者状况有很好的了解，并且采取筛查和治疗来有效预防结肠癌。
研究当中的犹他州家族有超过7000名后代跨越了九代，这些都记录在犹他州人口数据库(UPDB) ，研究者利用该数据库以确定和研究某些家族有高发病率的癌症或其他疾病，用以分析遗传的模式并确定具体的遗传突变。在犹他州，从1966年至1995年这个家族中记录在案个体患结肠癌率为0.15 ％。基于这个比例，研究人员推测在1966到2003年中报道的5000例结肠癌中出自该家族的会有八例。但之前的研究已证实此家族人员通过采取有效的临床干预，在此期间只有一例该家族的人员被诊断出是突变携带者。
研究人认为虽然有效地预防了另外七个可能患癌症的潜在患者也许听起来不多，但是毕竟避免了他们患病会给家庭造成的经济负担，保守的估计每例直肠癌治疗成本为5万美元，这就意味着无形当中就为这些家庭省下了35万美元的巨额开销。（科学网 于乃森 编译）
生物谷推荐原始出处：
doi:10.1016/j.cgh.2007.09.017
Original article—alimentary tract
American Founder Mutation for Attenuated Familial Adenomatous Polyposis
Deborah W. Neklason, ‡, , , Jeffery Stevens§, Kenneth M. Boucher, ‡, Richard A. Kerber, ‡, Nori Matsunami§, Jahn Barlow‡, Geraldine Mineau, ‡, Mark F. Leppert§ and Randall W. Burt‡,
‡Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah
Department of Oncological Sciences, University of Utah, Salt Lake City, Utah
Department of Medicine, University of Utah, Salt Lake City, Utah
§Department of Human Genetics, University of Utah, Salt Lake City, Utah
Available online 11 December 2007.
Background & Aims: Specific mutations in the adenomatous polyposis coli (APC) gene can lead to an attenuated form of familial adenomatous polyposis (AFAP). Although AFAP mutation carriers have a 69% risk of colorectal cancer by age 80, clinical recognition remains a challenge in some cases because they present with few colonic adenomas and are difficult to distinguish clinically from patients with sporadic polyps. Methods: Family relationships were established using family history reports, the Utah Population Database, and the public records of the Mormon Church. Genetic analysis of representative family members was performed using a 10,000 single nucleotide polymorphism array platform. Colonoscopy data were available on 120 individuals with the AFAP mutation. Results: Two large AFAP kindreds with the identical APC disease-causing mutation (c.426_427delAT) were linked to a founding couple who came to America from England around 1630. Genetic analysis showed that the 2 families share a conserved haplotype of 7.17 Mbp surrounding the mutant APC allele. The data show that 36.6% of the mutation-positive family members have fewer than 10 colonic adenomatous polyps, and 3 (6.8%) of these individuals were diagnosed with colorectal cancer. Conclusions: In view of the apparent age of this mutation, a notable fraction of both multiple-adenoma patients and perhaps even colon cancer cases in the United States could be related to this founder mutation. The colon cancer risk associated with the mutation makes genetic testing of considerable importance in patients with a personal or family history of either colonic polyps or cancer at a young age.
Abbreviations: AFAP, attenuated familial adenomatous polyposis; APC, adenomatous polyposis coli; CI, confidence interval; FAP, familial adenomatous polyposis; SNP, single nucleotide polymorphism
This research is supported by National Cancer Institute grants P01-CA073992 (R.W.B.) R01-CA040641 (R.W.B.), the Utah Cancer Registry, which is funded by contract number NCI-CN-67000, the Utah Department of Health, the University of Utah, and the Huntsman Cancer Foundation. Partial support of Utah Population Database is provided by the University of Utah and Huntsman Cancer Institute.
Address requests for reprints to: Deborah W. Neklason, PhD, 2000 Circle of Hope, Room 4122, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah 84112-5550. fax: (801) 585-5763.
