The BRCA2 372 HH genotype is associated with risk of breast cancer in Australian women under age 60 years.
The BRCA2 N372H nonconservative amino acid substitution polymorphism appears to affect fetal survival in a sex-dependent manner, and the HH genotype was found to be associated with a 1.3-fold risk of breast cancer from pooling five case-control studies of Northern European women. We investigated whether the BRCA2 N372H polymorphism was associated with breast cancer in Australian women using a population-based case-control design. The BRCA2 372 genotype was determined in 1397 cases under the age of 60 years at diagnosis of a first primary breast cancer and in 775 population-sampled controls frequency matched for age. Case-control analyses and comparisons of genotype distributions were conducted using logistic regression. All of the statistical tests were two-tailed. The HH genotype was independent of age and family history of breast cancer within cases and controls, and was more common in cases (9.2% versus 6.5%). It was associated with an increased risk of breast cancer, 1.47-fold unadjusted (95% confidence interval, 1.05-2.07; P = 0.02), and 1.42-fold (95% confidence interval, 1.00-2.02; P = 0.05) after adjusting for measured risk factors. This effect was still evident after excluding women with any non-Caucasian ancestry or the 33 cases known to have inherited a mutation in BRCA1 or BRCA2, and would explain approximately 3% of breast cancer. The BRCA2 N372H polymorphism appears to be associated with a modest recessively inherited risk of breast cancer in Australian women. This result is consistent with the findings for Northern European women.
Spurdle
Amanda B
AB
Oncology Division, Joint Experimental Oncology Programme, The Queensland Institute of Medical Research and The University of Queensland, Brisbane, 4029 Australia. mandyS@qimr.edu.au
Hopper
John L
JL
Chen
Xiaoqing
X
Dite
Gillian S
GS
Cui
Jisheng
J
McCredie
Margaret R E
MR
Giles
Graham G
GG
Ellis-Steinborner
Sarah
S
Venter
Deon J
DJ
Newman
Beth
B
Southey
Melissa C
MC
Chenevix-Trench
Georgia
G
D000328:Adult; D017668:Age of Onset; D019943:Amino Acid Substitution; D001315:Australia / Q000453:epidemiology; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D010375:Pedigree; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D012307:Risk Factors
D024682:BRCA2 Protein