Breast cancer risk factors differ between Asian and white women with BRCA1/2 mutations.
The prevalence and penetrance of BRCA1 and BRCA2 (BRCA1/2) mutations may differ between Asians and whites. We investigated BRCA1/2 mutations and cancer risk factors in a clinic-based sample. BRCA1/2 mutation carriers were enrolled from cancer genetics clinics in Hong Kong and California according to standardized entry criteria. We compared BRCA mutation position, cancer history, hormonal and reproductive exposures. We analyzed DNA samples for single-nucleotide polymorphisms reported to modify breast cancer risk. We performed logistic regression to identify independent predictors of breast cancer. Fifty Asian women and forty-nine white American women were enrolled. BRCA1 mutations were more common among whites (67 vs. 42 %, p = 0.02), and BRCA2 mutations among Asians (58 vs. 37 %, p = 0.04). More Asians had breast cancer (76 vs. 53 %, p = 0.03); more whites had relatives with breast cancer (86 vs. 50 %, p = 0.0003). More whites than Asians had breastfed (71 vs. 42 %, p = 0.005), had high BMI (median 24.3 vs. 21.2, p = 0.04), consumed alcohol (2 drinks/week vs. 0, p < 0.001), and had oophorectomy (61 vs. 34 %, p = 0.01). Asians had a higher frequency of risk-associated alleles in MAP3K1 (88 vs. 59 %, p = 0.005) and TOX3/TNRC9 (88 vs. 55 %, p = 0.0002). On logistic regression, MAP3K1 was associated with increased breast cancer risk for BRCA2, but not BRCA1 mutation carriers; breast density was associated with increased risk among Asians but not whites. We found significant differences in breast cancer risk factors between Asian and white BRCA1/2 mutation carriers. Further investigation of racial differences in BRCA1/2 mutation epidemiology could inform targeted cancer risk-reduction strategies.
Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Monique A
MA
de Bruin
Ava
A
Kwong
Benjamin A
BA
Goldstein
Jafi A
JA
Lipson
Debra M
DM
Ikeda
Lisa
L
McPherson
Bhavna
B
Sharma
Ani
A
Kardashian
Elizabeth
E
Schackmann
Kerry E
KE
Kingham
Meredith A
MA
Mills
Dee W
DW
West
James M
JM
Ford
Allison W
AW
Kurian
D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001942:Breast Feeding / Q000706:statistics & numerical data; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D002140:California; D005260:Female; D020022:Genetic Predisposition to Disease; D006723:Hong Kong; D006801:Humans; D008019:Life Style; D016015:Logistic Models; D048728:MAP Kinase Kinase Kinase 1 / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D010052:Ovariectomy; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D044465:White People / Q000235:genetics*
D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D048728:MAP Kinase Kinase Kinase 1; C482576:MAP3K1 protein, human