生物谷報道：美國的一項最新研究結果顯示，女性的乳腺癌基因也可遺傳自父親,。
美國《芝加哥論壇報》網(wǎng)絡版日前報道，美國每年約有８０００人患乳腺癌,，而數(shù)以千計患乳腺癌的年輕女子未做過檢測確定患病基因和治療方案,。這種檢測費用超過３０００美元。
參與研究的杰弗里·韋策爾博士說,，保險公司用來確定基因檢測范圍的指導原則應當修改以體現(xiàn)這些研究成果,。
韋策爾說：“有趣的是它跟父親有關。”在患遺傳性乳腺癌女性當中,，有一半是從父親而不是母親那里遺傳的,。但假如父親沒有女性親屬患乳腺癌，故障基因就可能無聲無息地一代一代傳下去而不引起癌癥,。男性也會患遺傳性乳腺癌,，但不常見。韋策爾表示,，醫(yī)生通常忽視父系的基因風險。
《美國醫(yī)學會雜志》周刊日前發(fā)表的研究報告分析了３０６名５０歲之前患乳腺癌的女性的基因檢測結果,。這些患者都沒有乳腺癌或卵巢癌家族史,。在有眾多女性親戚的患者中，約５％的人有ＢＲＣＡ基因突變,。但在４５歲以上（乳腺癌高發(fā)年齡段）,、姐姐和姑姑極少（兩個以下）的患者當中，約１４％的人有ＢＲＣＡ１或ＢＲＣＡ２基因突變,。這說明,，這些癌癥患者不知道自己有基因突變是因為家族中極少有女性顯示出癌癥風險。（引自新華網(wǎng)）
原始出處:
JAMA,，The Journal of the American Medical Association
Vol. 297 No. 21, June 6, 2007
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.
