Absence of founder BRCA1 and BRCA2 mutations in cutaneous malignant melanoma patients of Ashkenazi origin.
BACKGROUND
Several epidemiologic studies have provided suggestive evidence of a link between coetaneous malignant melanoma (CMM) and breast cancer. The Breast Cancer Linkage Consortium (BCLC) reported approximately 2.6-fold increase in the risk for CMM among BRCA2 carrier families.


METHODS
To evaluate the role of BRCA1/2 mutations in CMM, we screened 92 Jewish patients of Ashkenazi origin diagnosed with CMM for the three Ashkenazi founder mutations: 185delAG and 5382insC in the BRCA1 and 6174delT in the BRCA2 gene. Information about personal demography, family history of cancer, and occupational and lifestyle history was collected.


RESULTS
Thirty-seven of 92 (40.2%) CMM patients reported a family history of cancer in a first-degree relative. In 14 patients, history of breast cancer (BC) was recorded; however, no family had features associated with BRCA carrier status (i.e., young age at BC onset, history of several BC cases or ovarian cancer in the family). None of the patients were found to carry any of these three mutations.


CONCLUSIONS
Our results suggest a limited role for the three Ashkenazi BRCA founder mutations in CMM risk among the Ashkenazi Jewish population. Therefore, screening patients with CMM for these BRCA1/2 mutations is not warranted.
Kadouri
Luna
L
Sharett Institute of Oncology, Hebrew University-Hadassah Medical Center, Jerusalem, 91120, Israel. luna@hadassah.org.il
Temper
Mark
M
Grenader
Tal
T
Abeliovich
Dvorah
D
Hamburger
Tamar
T
Peretz
Tamar
T
Lotem
Michal
M
D001943:Breast Neoplasms / Q000235:genetics; D005260:Female; D018703:Founder Effect; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D006801:Humans; D007585:Jews / Q000235:genetics; D008297:Male; D008545:Melanoma / Q000235:genetics*; D009154:Mutation; D016133:Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000235:genetics*; D044465:White People / Q000235:genetics