Purpose: The identification of a BRCA1 or BRCA2 genetic mutation can provide important health information to individuals who receive this result, but it can also provide crucial cancer risk information to family members. Most of the research on communication of genetic test results has focused on first degree relatives. The purpose of this retrospective study was to examine the process of communicating a positive BRCA1 or BRCA2 genetic test result to male and female first, second, and third degree relatives. Methods: Participants were 38 female mutation carriers who responded to a written survey assessing the number and relationship of relatives informed, methods used to inform relatives, topics discussed, and motivations and barriers for communication. Results: Overall, 59%(470/803) of first, second, and third degree relatives were informed. The proportion of informed parents, siblings, and offspring was nearly twice that of more distant relatives including nieces, nephews, aunts, uncles, grandchildren, and cousins (88% versus 45%; P ϭ 0.02). The method of communication differed by the gender of the relative, as did some of the topics discussed. The most important reasons for discussing the genetic test results were (1) to inform the relatives of their risk, (2) to suggest that they be tested, and (3) to fulfill a perceived duty to inform. The major barrier to communication was little contact and/or emotionally distant relationships. Genetic information is rapidly becoming an integral part of clinical management for numerous medical conditions. The current medical model limits the delivery of genetic information to the individual seeking services, when in reality the information has implications for the entire family. Because of confidentiality, privacy issues, and health care regulations, the responsibility for sharing genetic test results with relatives falls on the index patient who may not be prepared or willing to assume this role. Understanding the determinants of communication about genetic test results will assist health care providers in addressing this critical issue.Previous research studies have explored family communication about a variety of genetic conditions; however, the bulk of research on family communication with regard to genetic testing has focused on hereditary breast and ovarian cancer syndrome. [1][2][3][4][5][6][7][8][9] This is likely due to the increased availability and utilization of cancer genetic counseling services as well as the complex clinical and psychological issues related to testing for cancer risk. 10 -12 Two major breast cancer genes, BRCA1 and BRCA2, are responsible for 5% to 10% of breast and ovarian cancer cases. Mutations in these genes are inherited in an autosomal dominant manner and confer an inherited predisposition to breast, ovarian, and other cancers. [13][14][15] DNA-based testing for BRCA1 and BRCA2 cancer-predisposing mutations is available on a clinical basis. The identification of a disease-associated mutation in an individual allows for predictive test...

Purpose: To identify germ line CDH1 mutations in hereditary diffuse gastric cancer (HDGC) families and develop guidelines for management of at risk individuals. Experimental Design: We ascertained 31 HDGC previously unreported families, including 10 isolated early-onset diffuse gastric cancer (DGC) cases. Screening for CDH1 germ line mutations was done by denaturing high-performance liquid chromatography and automated DNA sequencing. Results: We identified eight inactivating and one missense CDH1 germ line mutation. The missense mutation conferred in vitro loss of protein function. Two families had the previously described 1003C>T nonsense mutation. Haplotype analysis revealed this to be a recurrent and not a founder mutation. Thirty-six percent (5 of 14) of the families with a documented DGC diagnosed before the age of 50 and other cases of gastric cancer carried CDH1 germ line mutations. Two of10 isolated cases of DGC in individuals ages <35 years harbored CDH1germ line mutations. One mutation positive family was ascertained through a family history of lobular breast cancer (LBC) and another through an individual with both DGC and LBC. Occult DGC was identified in five of six prophylactic gastrectomies done on asymptomatic, endoscopically negative 1003C>T mutation carriers. Conclusions: In addition to families with a strong history of early-onset DGC, CDH1 mutation screening should be offered to isolated cases of DGC in individuals ages <35 years and for families with multiple cases of LBC, with any history of DGC or unspecified GI malignancies. Prophylactic gastrectomy is potentially a lifesaving procedure and clinical breast screening is recommended for asymptomatic mutation carriers.Gastric cancer is one of the three leading causes of cancer death worldwide (1). Although the incidence of gastric cancer in older patients is decreasing, in younger patients as well as in cases with familial clustering it remains stable, suggesting that genetic predisposition is an increasingly important risk factor for gastric cancer (2). In this respect, as few as 1% to 3% of all