2008年1月的愛(ài)思唯爾期刊《臨床腸胃病學(xué)與肝臟病學(xué)》（Clinical Gastroenterology and Hepatology）刊登了美國(guó)猶他州大學(xué)亨斯邁癌癥研究所（Huntsman Cancer Institute）關(guān)于探尋現(xiàn)今美國(guó)結(jié)腸癌病源頭的研究?？茖W(xué)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(gè)家族,。研究發(fā)現(xiàn)這兩個(gè)家族竟然有著共同的祖先,。研究人員認(rèn)為，這同時(shí)也意味著會(huì)有更多的美國(guó)家庭攜帶著這個(gè)基因,，此外這個(gè)基因突變可能與許多美國(guó)現(xiàn)今結(jié)腸癌的病例都有一定關(guān)聯(lián),。該基因突變會(huì)引起一種名為衰減家族性腺瘤性息肉病(AFAP)的疾病。在沒(méi)有適當(dāng)?shù)呐R床護(hù)理下,，攜有AFAP突變的人群在80歲時(shí)會(huì)有非常高的幾率患結(jié)腸癌,，平均每3個(gè)人中就會(huì)有兩個(gè)患病，遠(yuǎn)遠(yuǎn)高于正常的每24個(gè)人會(huì)有1個(gè)人患病的幾率,。
研究人員認(rèn)為,，患者應(yīng)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(huì)在突變攜帶者20歲后診斷出,，結(jié)腸癌也已能在20多歲時(shí)候確診,。但是研究人員解釋?zhuān)R床診斷出AFAP卻很困難，因?yàn)榻Y(jié)腸癌的病發(fā)一般在50多歲左右,，同時(shí)也具有偶發(fā)性的和非遺傳性,。研究人員認(rèn)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(yīng)該對(duì)AFAP有清醒的認(rèn)識(shí) ,，對(duì)患者狀況有很好的了解，并且采取篩查和治療來(lái)有效預(yù)防結(jié)腸癌,。
研究當(dāng)中的猶他州家族有超過(guò)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(kù)(UPDB) ，研究者利用該數(shù)據(jù)庫(kù)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(gè)家族中記錄在案?jìng)€(gè)體患結(jié)腸癌率為0.15 ％,?；谶@個(gè)比例，研究人員推測(cè)在1966到2003年中報(bào)道的5000例結(jié)腸癌中出自該家族的會(huì)有八例。但之前的研究已證實(shí)此家族人員通過(guò)采取有效的臨床干預(yù),，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(rèn)為雖然有效地預(yù)防了另外七個(gè)可能患癌癥的潛在患者也許聽(tīng)起來(lái)不多，但是畢竟避免了他們患病會(huì)給家庭造成的經(jīng)濟(jì)負(fù)擔(dān),，保守的估計(jì)每例直腸癌治療成本為5萬(wàn)美元,，這就意味著無(wú)形當(dāng)中就為這些家庭省下了35萬(wàn)美元的巨額開(kāi)銷(xiāo)。（科學(xué)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.
