Polymorphisms in BRCA1 and BRCA2 and risk of epithelial ovarian cancer.
OBJECTIVE
Because inherited BRCA1 or BRCA2 mutations strikingly increase ovarian cancer risk, polymorphisms in these genes could represent low penetrance susceptibility alleles. Previous studies of the BRCA2 N372H polymorphism suggested that HH homozygotes have a modestly increased risk of both breast and ovarian cancer. We have examined whether BRCA2 N372H or common amino acid-changing polymorphisms in BRCA1 predispose to ovarian cancer.


METHODS
A population-based, case control study of ovarian cancer was performed in North Carolina. Cases included 312 women with ovarian cancer (76% invasive and 24% borderline) and 401 age- and race-matched controls. Blood DNA from subjects was genotyped for BRCA2 N372H and BRCA1 Q356R and P871L.


RESULTS
There was no association between BRCA2 N372H and risk of borderline or invasive epithelial ovarian cancer. The overall odds ratio (OR) for HH homozygotes was 0.8 [95% confidence interval (CI) = 0.4-1.5] and was similar in all subsets, including invasive serous cases. In addition, neither the BRCA1 Q356R (OR = 0.9, 95% CI 0.5-1.4) nor P871L (OR = 0.9, 95% CI 0.6-1.9) polymorphisms were associated with ovarian cancer risk. There was a significant racial difference in allele frequencies of the P871L polymorphism (P = 0.64 in Caucasians, L = 0.76 in African-Americans, P < 0.0001).


CONCLUSIONS
In this population-based, case control study, common amino acid changing BRCA1 and 2 polymorphisms were not found to affect the risk of developing ovarian cancer.
Wenham
Robert M
RM
Department of Obstetrics and Gynecology/Division of Gynecologic Oncology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Schildkraut
Joellen M
JM
McLean
Kia
K
Calingaert
Brian
B
Bentley
Rex C
RC
Marks
Jeffrey
J
Berchuck
Andrew
A
D018262:Adenocarcinoma, Clear Cell / Q000453:epidemiology / Q000235:genetics; D002288:Adenocarcinoma, Mucinous / Q000453:epidemiology / Q000235:genetics; D000328:Adult; D000368:Aged; D018269:Carcinoma, Endometrioid / Q000453:epidemiology / Q000235:genetics; D016022:Case-Control Studies; D018284:Cystadenocarcinoma, Serous / Q000453:epidemiology / Q000235:genetics; D004247:DNA / Q000097:blood / Q000235:genetics; D004252:DNA Mutational Analysis; D005006:Ethnicity / Q000235:genetics; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009375:Neoplasms, Glandular and Epithelial / Q000453:epidemiology / Q000235:genetics*; D009657:North Carolina / Q000453:epidemiology; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors
D004247:DNA