生物谷报道：美国的一项最新研究结果显示，女性的乳腺癌基因也可遗传自父亲。
美国《芝加哥论坛报》网络版日前报道，美国每年约有８０００人患乳腺癌，而数以千计患乳腺癌的年轻女子未做过检测确定患病基因和治疗方案。这种检测费用超过３０００美元。
参与研究的杰弗里·韦策尔博士说，保险公司用来确定基因检测范围的指导原则应当修改以体现这些研究成果。
韦策尔说：“有趣的是它跟父亲有关。”在患遗传性乳腺癌女性当中，有一半是从父亲而不是母亲那里遗传的。但假如父亲没有女性亲属患乳腺癌，故障基因就可能无声无息地一代一代传下去而不引起癌症。男性也会患遗传性乳腺癌，但不常见。韦策尔表示，医生通常忽视父系的基因风险。
《美国医学会杂志》周刊日前发表的研究报告分析了３０６名５０岁之前患乳腺癌的女性的基因检测结果。这些患者都没有乳腺癌或卵巢癌家族史。在有众多女性亲戚的患者中，约５％的人有ＢＲＣＡ基因突变。但在４５岁以上（乳腺癌高发年龄段）、姐姐和姑姑极少（两个以下）的患者当中，约１４％的人有ＢＲＣＡ１或ＢＲＣＡ２基因突变。这说明，这些癌症患者不知道自己有基因突变是因为家族中极少有女性显示出癌症风险。（引自新华网）
原始出处:
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.
