生物谷報(bào)道：
胃癌是我國(guó)最常見(jiàn)的惡性腫瘤之一 ,在我國(guó)其發(fā)病率居各類腫瘤的首位 ,每年約有 17 萬(wàn)人死于胃癌 ,幾乎接近全部惡性腫瘤死亡人數(shù)的1/4 ,且每年還有 2 萬(wàn)以上新的胃癌病人產(chǎn)生出來(lái) ,胃癌確實(shí)是一種嚴(yán)重威脅人民身體健康的疾病,。
發(fā)表在6月6日的JAMA雜志上的一項(xiàng)研究結(jié)果顯示,，研究人員確定出一種與遺傳性彌散型胃癌有關(guān)的新基因突變。
胃癌是全世界因癌癥死亡病例的第二大原因,，主要有兩種類型：一種腸型,，另一種是彌散型。遺傳性彌散型胃癌（HDGC）是有CDH1基因的突變引起的,。CDH1突變的確定增加了研發(fā)降低癌癥風(fēng)險(xiǎn)的治療方法的機(jī)會(huì),。
Pardeep Kaurah和同事對(duì)CDH1基因的突變頻率進(jìn)行了評(píng)估,，并且還對(duì)這些突變是因?yàn)楠?dú)立突變事件或共同血統(tǒng)而導(dǎo)致的問(wèn)題進(jìn)行了研究。該研究對(duì)38個(gè)有患有HDGC成員的家庭進(jìn)行了CDH1突變分析,。
研究證實(shí)30％到40％的具有胃癌史的家庭和超過(guò)50％的出現(xiàn)過(guò)兩個(gè)彌散型胃癌病例的家庭攜帶了CDH1基因突變,。接下來(lái)，研究人員將會(huì)進(jìn)行更多范圍的研究,。而這些初步的數(shù)據(jù)則顯示出了CDH1基因突變與胃癌的相關(guān)程度,。
原始出處:
Founder and Recurrent CDH1 Mutations in Families With Hereditary Diffuse Gastric Cancer
Pardeep Kaurah, MSc; Andrée MacMillan, MSc; Niki Boyd, MSc, PhD; Janine Senz, BSc; Alessandro De Luca, BSc; Nicki Chun, MS; Gianpaolo Suriano, PhD; Sonya Zaor, MSc; Lori Van Manen, MS; Cathy Gilpin, MS; Sarah Nikkel, MD; Mary Connolly-Wilson, Med; Scott Weissman, MS; Wendy S. Rubinstein, MD; Courtney Sebold, MS; Robert Greenstein, MD; Jennifer Stroop, MS; Dwight Yim, MD; Benoit Panzini, MD; Wendy McKinnon, MS; Marc Greenblatt, MD; Debrah Wirtzfeld, MD; Daniel Fontaine, MD; Daniel Coit, MD; Sam Yoon, MD; Daniel Chung, MD; Gregory Lauwers, MD; Antonio Pizzuti, MD; Carlos Vaccaro, MD; Maria Ana Redal, PhD; Carla Oliveira, PhD; Marc Tischkowitz, MD; Sylviane Olschwang, MD; Steven Gallinger, MD; Henry Lynch, MD; Jane Green, PhD; James Ford, MD; Paul Pharoah, PhD; Bridget Fernandez, MD; David Huntsman, MD
JAMA. 2007;297:2360-2372. Published online June 3, 2007 (doi:10.1001/jama.297.21.2360).
Context Hereditary diffuse gastric cancer is caused by germline mutations in the epithelial cadherin (CDH1) gene and is characterized by an increased risk for diffuse gastric cancer and lobular breast cancer.
Objective To determine whether recurring germline CDH1 mutations occurred due to independent mutational events or common ancestry.
Design, Setting, and Patients Thirty-eight families diagnosed clinically with hereditary diffuse gastric cancer were accrued between November 2004 and January 2006 and were analyzed for CDH1 mutations as part of an ongoing study at the British Columbia Cancer Agency. Twenty-six families had at least 2 gastric cancer cases with 1 case of diffuse gastric cancer in a person younger than 50 years; 12 families had either a single case of diffuse gastric cancer diagnosed in a person younger than 35 years or multiple cases of diffuse gastric cancer diagnosed in persons older than 50 years.
Main Outcome Measures Classification of family members as carriers or noncarriers of CDH1 mutations. Haplotype analysis to assess recurring mutations for common ancestry was performed on 7 families from this study and 7 previously reported families with the same mutations.
Results Thirteen mutations (6 novel) were identified in 15 of the 38 families (40% detection rate). The 1137G>A splicing mutation and the 1901C>T (A634V) missense/splicing mutation occurred on common haplotypes in 2 families but on different haplotypes in a third family. The 2195G>A (R732Q) missense/splicing mutation occurred in 2 families on different haplotypes. The 2064-2065delTG mutation occurred on a common haplotype in 2 families. Two families from this study plus 2 additional families carrying the novel 2398delC mutation shared a common haplotype, suggesting a founder effect. All 4 families originate from the southeast coast of Newfoundland. Due to concentrations of lobular breast cancer cases, 2 branches of this family had been diagnosed as having hereditary breast cancer and were tested for BRCA mutations. Within these 4 families, the cumulative risk by age 75 years in mutation carriers for clinically detected gastric cancer was 40% (95% confidence interval [CI], 12%-91%) for males and 63% (95% CI, 19%-99%) for females and the risk for breast cancer in female mutation carriers was 52% (95% CI, 29%-94%).
Conclusions Recurrent CDH1 mutations in families with hereditary diffuse gastric cancer are due to both independent mutational events and common ancestry. The presence of a founder mutation from Newfoundland is strongly supported.
