Estrogen metabolizing polymorphisms and breast cancer risk among older white women.
OBJECTIVE
To investigate breast cancer risk according to metabolizing genes polymorphisms in older women.


METHODS
A subset (43.8%) of 4248 older, white women from the Study of Osteoporotic Fractures (SOF) were genotyped for the catechol-O-methyltransferase (COMT) Val108Met polymorphism and the CYP1A1*2C locus. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between genotypes and breast cancer while controlling for potential confounders.


RESULTS
During a mean follow up of 12.4 years, 252 women (5.9%) developed breast cancer. The HR (95% CI) for breast cancer was 1.24 (0.87-1.75) for COMT(Val/Met) and 1.35 (0.93-1.97) for COMT(Met/Met). No interactions with lifestyle and reproductive factors were found. The HR associated with the CYP1A1*2C Val allele was 0.80 (0.46, 1.39) with little evidence for interactions with lifestyle or reproductive factors.


CONCLUSIONS
Among older white women, neither the COMT Val108/158Met polymorphism nor the CYP1A*2C Val allele plays a major role in breast cancer risk either alone or in combination with lifestyle and reproductive factors.
Modugno
Francesmary
F
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, PA, USA. modugno+@pitt.edu
Zmuda
Joseph M
JM
Potter
Douglas
D
Cai
Chao
C
Ziv
Elad
E
Cummings
Steven R
SR
Stone
Katie L
KL
Morin
Phillip A
PA
Greene
Deborah
D
Cauley
Jane A
JA
D000368:Aged; D001943:Breast Neoplasms / Q000208:ethnology / Q000235:genetics*; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D004967:Estrogens / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D008019:Life Style; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D011446:Prospective Studies; D017584:Reproductive History; D012306:Risk; D014481:United States / Q000453:epidemiology; D044465:White People / Q000235:genetics*
D004967:Estrogens; D019363:Cytochrome P-450 CYP1A1; D002394:Catechol O-Methyltransferase