title: The BRCA2 372 HH genotype is associated with risk of breast cancer in Australian women under age 60 years.
abstract: 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.
authors.affiliation: Oncology Division, Joint Experimental Oncology Programme, The Queensland Institute of Medical Research and The University of Queensland, Brisbane, 4029 Australia. mandyS@qimr.edu.au
authors.forename: Amanda B
authors.initials: AB
authors.lastname: Spurdle
authors.forename: John L
authors.initials: JL
authors.lastname: Hopper
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Chen
authors.forename: Gillian S
authors.initials: GS
authors.lastname: Dite
authors.forename: Jisheng
authors.initials: J
authors.lastname: Cui
authors.forename: Margaret R E
authors.initials: MR
authors.lastname: McCredie
authors.forename: Graham G
authors.initials: GG
authors.lastname: Giles
authors.forename: Sarah
authors.initials: S
authors.lastname: Ellis-Steinborner
authors.forename: Deon J
authors.initials: DJ
authors.lastname: Venter
authors.forename: Beth
authors.initials: B
authors.lastname: Newman
authors.forename: Melissa C
authors.initials: MC
authors.lastname: Southey
authors.forename: Georgia
authors.initials: G
authors.lastname: Chenevix-Trench
mesh_terms: 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
chemical_list: D024682:BRCA2 Protein