Associations between single nucleotide polymorphisms in double-stranded DNA repair pathway genes and familial breast cancer.
OBJECTIVE
DNA damage recognition and repair play a major role in risk for breast cancer. We investigated 104 single nucleotide polymorphisms (SNP) in 17 genes whose protein products are involved in double-stranded break repair (DSBR).


METHODS
We used a case-control design. Both the case individuals affected with breast cancer or with both breast and ovarian cancers and the controls had similar familial risk of breast cancer and were participants in a high-risk cancer registry.


RESULTS
We found that 12 of the polymorphisms are associated with breast or breast and ovarian cancers, most notably rs16888927, rs16888997, and rs16889040, found in introns of RAD21, suggesting that SNPs in other genes in the DSBR pathway in addition to BRCA1 and BRCA2 may affect breast cancer risk.


CONCLUSIONS
SNPs within or near several DSBR DNA repair pathway genes are associated with breast cancer in individuals from a high-risk population. In addition, our study reemphasizes the unique perspective that recruitment of cases and controls from family cancer registries has for gene discovery studies.
Sehl
Mary E
ME
Divisions of Hematology and Oncology and Geriatrics, Department of Medicine, David Geffen School of Medicine at University of California at Los Angeles, USA. msehl@mednet.ucla.edu
Langer
Lucy R
LR
Papp
Jeanette C
JC
Kwan
Lorna
L
Seldon
Joyce L
JL
Arellano
Geovanni
G
Reiss
Jean
J
Reed
Elaine F
EF
Dandekar
Sugandha
S
Korin
Yael
Y
Sinsheimer
Janet S
JS
Zhang
Zuo-Feng
ZF
Ganz
Patricia A
PA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D018797:Cell Cycle Proteins; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; C429022:RAD21 protein, human; C101467:XRCC4 protein, human