abstract: BRCA genetic testing of individuals from families with low prevalence of cancer: experiences of carriers and implications for population screening : small study 14 Ashkenazi Jewish women

BRCA genetic testing of individuals from families with low prevalence of cancer: experiences of carriers and implications for population screening : Genetics in Medicine : Nature Publishing Group

Purpose:

BRCA genes are associated with hereditary breast and ovarian cancers. Guidelines worldwide currently recommend BRCA genetic testing in asymptomatic individuals only if they belong to “high-risk” families. However, population screening for BRCA1/2 may be the logical next step in populations with a high prevalence of founder mutations, such as Ashkenazi Jews. This study aimed to explore (i) the impact of a positive BRCA genetic test result on individuals who have neither a personal history nor a familial history of cancer and (ii) their attitudes toward the concept of population screening.

Methods:

Semistructured in-depth interviews were carried out with 14 Ashkenazi Jewish women who were asymptomatic BRCA carriers and who belonged to families with low prevalence of cancer.

Results:

Three main findings emerged: (i) having no family history of cancer was a source of optimism but also confusion; (ii) engaging in intensified medical surveillance and undergoing preventive procedures was perceived as health-promoting but also tended to induce a sense of physical and psychological vulnerability; and (iii) there was overall support for BRCA population screening, with some reservations.

Conclusion:

Women belonging to low-cancer-prevalence families within a “high-risk” ethnic community view BRCA genetic testing positively despite the difficulties entailed, because it allows prevention or early detection of cancer. However, implementing a BRCA population screening program should be carried out with proper pre- and post-testing preparation and support for the individuals undergoing testing.

Clinical Oncology News - Triple-Negative Breast Cancers Associated With Ashkenazi Origin

The founder Ashkenazi Jewish mutations in the MSH2 and MSH6 genes in Israeli patients with gastric and pancreatic cancer

Abstract

The genetic basis for gastric and pancreatic cancer is largely undetermined.
These cancers are overrepresented in hereditary non polyposis colon cancer (HNPCC), inherited cancer syndrome attributed to germline mutations primarily in the MSH2, MLH1 and MSH6 genes.
Among Ashkenazi Jewish HNPCC cases, recurring mutations in the MSH2 (1906G>C; A636P) and MSH6 (c.3984_3987dupGTCA; c.3959_3962delCAAG) genes can be detected. The MSH6*c.3984_3987dupGTCA mutation was recently detected in an Ashkenazi family with inherited gastric cancer. We hypothesized that it may be possible to detect the recurring MSH2 and MSH6 mutations in Jewish individuals with familial and sporadic gastric and pancreatic cancer.
To test this notion, we genotyped 143 unrelated Jewish Israeli patients with gastric (n = 23) and pancreatic (n = 120) cancer. The majority of cases (100/143–70%) were Ashkenazi Jews, and 10% (n = 16)—of mixed Ashkenazi-non Ashkenazi Jewish ancestry, and most participants (n = 96–67.1%) had a positive family history of cancer. Genotyping the MSH2*A636P mutation was performed by PCR followed by restriction enzyme digest, and the MSH6*c.3984_3987dupGTCA and c.3959_3962delCAAG mutations were detected by fragment size analysis by capillary electrophoresis and sequencing. None of the participants harbored any of the genotyped MSH2 or MSH6 mutations.
We conclude that the recurring Ashkenazi MSH2 and MSH6 mutations contribute little if any to sporadic and familial gastric and pancreatic cases in Israeli patients"

Abstract/full free access: BRCA in the Ashkenazi Population: Are Current Testing Guidelines Too Exclusive?

(The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production) 

Abstract:

 The BRCA1/2 genes account for a significant portion of hereditary breast and ovarian cancers and they are especially prevalent in the Ashkenazi Jewish population. Women who have a mutation can prevent breast and ovarian cancer with surgical intervention. We describe an Ashkenazi Jewish patient who illustrates that current testing criteria are too restrictive, particularly for this population of patients. The patient's sister was diagnosed with breast cancer at age 33; however, she was not a mutation carrier. Based on practice guidelines, the patient was not recommended genetic testing. She subsequently underwent direct-to-consumer (DTC) testing and discovered that she was a mutation carrier. This case demonstrates the need for clinicians to be aware of the higher prevalence of BRCA mutations in the Ashkenazi population. It also exemplifies the need to involve medical professionals, including genetic counselors, in the dissemination of DNA test results.

clinical trial: Anonymous Testing of Pathology Specimens for BRCA (and Lynch Syndrome MSH2) Mutations in Ashkenazi Jewish Individuals Who Have Cancer

Purpose

The intent of the proposed study is to describe the prevalence of the most common recurring mutations

in BRCA1 and BRCA2, blmAsh , and the A636P MSH2  (Lynch Syndrome) mutation among Ashkenazi Jewish individuals with a variety of cancer diagnoses. If a substantial proportion of these samples contain such mutations, future patients presenting with these diseases may wish to undergo genetic counseling and, if appropriate, formal genetic testing. The benefit from such a process would pertain mainly to the families of these individuals.

Condition
Extrahepatic Bile Duct Cancer Gallbladder Cancer Gastric Cancer Lung Cancer Melanoma Non-Hodgkin's Lymphoma Uterine Cancer CORPUS UTERI,ENDOMETRIUM LUNG OVARY

Identification of a Danish breast/ovarian cancer family double heterozygote for BRCA1 and BRCA2 mutations

Abstract
Mutations in the two breast cancer susceptibility genes BRCA1 and BRCA2 are associated with increased risk of breast and ovarian cancer. Patients with mutations in both genes are rarely reported and often involve Ashkenazi founder mutations. ......Since the BRCA1 Arg1699Gln mutation is also suggested to be disease-causing, we consider this family double heterozygote for BRCA1 and BRCA2 mutations.

Preventing Future Cancers by Testing Women With Ovarian Cancer for BRCA Mutations -- University of British Columbia/MD Anderson

"BRCA testing of women with ovarian cancer based on personal/family history of cancer or Ashkenazi Jewish ancestry is a cost-effective strategy to prevent future breast and ovarian cancers among FDRs (first degree relatives). More inclusive testing strategies prevent additional cancer cases but at significant cost."