Genetic polymorphisms in the catechol estrogen metabolism pathway and breast cancer risk.
BACKGROUND
This study investigated whether single nucleotide polymorphisms (SNP) in genes within the catechol estrogen metabolism pathway altered the risk of breast cancer alone or in combination, as well as whether menopausal hormone therapy modified the effect of these SNPs on breast cancer risk.


METHODS
In a population-based case-control study of breast cancer, 891 cases and 878 controls were genotyped for six functional SNPs in the COMT, CYP1B1, GSTM1, GSTP1, and GSTT1 genes.


RESULTS
Women homozygous with the T allele in CYP1B1*2 (Ser(119); rs1056827) were at 1.69 (95% confidence interval, 1.17-2.46) times the risk of women homozygous with the G allele; women homozygous with the G allele in GSTP1 (Val(105); rs1695) were at 0.73 (95% confidence interval, 0.54-0.99) times the risk of breast cancer compared with women homozygous with the A allele. No other SNPs tested were associated with breast cancer to any appreciable degree. Potential gene-gene and gene-hormone therapy interactions were investigated.


CONCLUSIONS
With the exception of GSTP1 and possibly CYP1B1*2, our findings do not provide support for the role of genetic variation in the catechol estrogen metabolism pathway and breast cancer risk in postmenopausal women.
Reding
Kerryn W
KW
University of Washington, Seattle, WA 98109, USA. kreding@u.washington.edu
Weiss
Noel S
NS
Chen
Chu
C
Li
Christopher I
CI
Carlson
Christopher S
CS
Wilkerson
Hui-Wen
HW
Farin
Federico M
FM
Thummel
Kenneth E
KE
Daling
Janet R
JR
Malone
Kathleen E
KE
D000368:Aged; D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics; D065633:Cytochrome P-450 CYP1B1; D002393:Estrogens, Catechol / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D051549:Glutathione S-Transferase pi / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause; D012306:Risk; D018426:SEER Program; D014861:Washington / Q000453:epidemiology
D001189:Aryl Hydrocarbon Hydroxylases; D002394:Catechol O-Methyltransferase; D065633:Cytochrome P-450 CYP1B1; D002393:Estrogens, Catechol; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C585496:CYP1B1 protein, human; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human