Risk of endometrial carcinoma associated with BRCA mutation.
OBJECTIVE
Inherited mutations in the BRCA1 or BRCA2 genes are associated with a greatly increased lifetime risk of breast and ovarian cancers and a modestly increased risk of several other cancer types. Several case reports of endometrial carcinoma in women with a BRCA mutation have led to speculation regarding the effect of these genes on the risk of endometrial cancer. The purpose of this study was to test the hypothesis that germline mutation of a BRCA gene is associated with an increased risk of endometrial carcinoma.


METHODS
A retrospective cohort of 199 consecutive Ashkenazi Jewish patients with endometrial carcinoma was identified from a 12-year period at this institution. All were genotyped for the three BRCA founder mutations (185delAG and 5382insC in BRCA1 and 6174delT in BRCA2) that exist in this population, and the case frequency was compared to the known population frequency of these mutations. Additionally, endometrial carcinomas occurring in patients with BRCA mutations were assessed for somatic loss of the wild-type BRCA allele.


RESULTS
Germline BRCA mutations were identified in 3 (1 in BRCA1 and two in BRCA2) of 199 (1.5%) patients, compared to a frequency of 2.0% in this population generally. A relative risk of endometrial carcinoma associated with BRCA mutation, as estimated by the odds ratio, was calculated as 0.75 (95% CI = 0.24--2.34; P = 0.6). Loss of the wild-type BRCA allele was observed in two of three tumors associated with a BRCA mutation.


CONCLUSIONS
For individuals with a germline BRCA mutation, the lifetime risk of endometrial carcinoma is not increased.
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
D A
DA
Levine
O
O
Lin
R R
RR
Barakat
M E
ME
Robson
D
D
McDermott
L
L
Cohen
J
J
Satagopan
K
K
Offit
J
J
Boyd
D000368:Aged; D000483:Alleles; D024682:BRCA2 Protein; D018269:Carcinoma, Endometrioid / Q000235:genetics / Q000473:pathology; D015331:Cohort Studies; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D019398:Genes, BRCA1 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D007585:Jews / Q000235:genetics*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D012189:Retrospective Studies; D014157:Transcription Factors / Q000235:genetics*
D024682:BRCA2 Protein; D009363:Neoplasm Proteins; D014157:Transcription Factors