2008年1月的愛思唯爾期刊《臨床腸胃病學與肝臟病學》（Clinical Gastroenterology and Hepatology）刊登了美國猶他州大學亨斯邁癌癥研究所（Huntsman Cancer Institute）關(guān)于探尋現(xiàn)今美國結(jié)腸癌病源頭的研究,。科學家發(fā)現(xiàn)了一種原始的基因突變,，很多現(xiàn)今的人群中的基因突變都可以追溯與此,。
研究人員研究了猶他州和紐約州攜帶有一種高幾率患結(jié)直腸癌的基因突變兩個家族。研究發(fā)現(xiàn)這兩個家族竟然有著共同的祖先,。研究人員認為,，這同時也意味著會有更多的美國家庭攜帶著這個基因，此外這個基因突變可能與許多美國現(xiàn)今結(jié)腸癌的病例都有一定關(guān)聯(lián),。該基因突變會引起一種名為衰減家族性腺瘤性息肉病(AFAP)的疾病,。在沒有適當?shù)呐R床護理下，攜有AFAP突變的人群在80歲時會有非常高的幾率患結(jié)腸癌，平均每3個人中就會有兩個患病,，遠遠高于正常的每24個人會有1個人患病的幾率,。
研究人員認為，患者應該知道自己的家族病史并盡早采取措施就可以有效地避免,。癌前息肉經(jīng)常會在突變攜帶者20歲后診斷出，結(jié)腸癌也已能在20多歲時候確診,。但是研究人員解釋,，臨床診斷出AFAP卻很困難，因為結(jié)腸癌的病發(fā)一般在50多歲左右,，同時也具有偶發(fā)性的和非遺傳性,。研究人員認為人們有必要跟他們的家人了解他們家庭癌癥史，并將此告知他們的醫(yī)生,。醫(yī)生應該對AFAP有清醒的認識 ,，對患者狀況有很好的了解，并且采取篩查和治療來有效預防結(jié)腸癌,。
研究當中的猶他州家族有超過7000名后代跨越了九代,，這些都記錄在猶他州人口數(shù)據(jù)庫(UPDB) ，研究者利用該數(shù)據(jù)庫以確定和研究某些家族有高發(fā)病率的癌癥或其他疾病,，用以分析遺傳的模式并確定具體的遺傳突變,。在猶他州，從1966年至1995年這個家族中記錄在案個體患結(jié)腸癌率為0.15 ％,?；谶@個比例，研究人員推測在1966到2003年中報道的5000例結(jié)腸癌中出自該家族的會有八例,。但之前的研究已證實此家族人員通過采取有效的臨床干預,，在此期間只有一例該家族的人員被診斷出是突變攜帶者。
研究人認為雖然有效地預防了另外七個可能患癌癥的潛在患者也許聽起來不多,，但是畢竟避免了他們患病會給家庭造成的經(jīng)濟負擔,，保守的估計每例直腸癌治療成本為5萬美元，這就意味著無形當中就為這些家庭省下了35萬美元的巨額開銷,。（科學網(wǎng) 于乃森 編譯）
生物谷推薦原始出處：
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.
