Effect modification by catalase genotype suggests a role for oxidative stress in the association of hormone replacement therapy with postmenopausal breast cancer risk.
Catalase, a ubiquitous heme enzyme, catalyzes conversion of hydrogen peroxide to water and molecular oxygen, protecting cells from oxidative stress. A C/T polymorphism in the promoter region of the CAT gene (rs1001179) affects transcriptional activity and RBC catalase levels. Oxidative stress may explain the observed increased postmenopausal breast cancer risk associated with hormone replacement therapy (HRT). We examined CAT genotype, HRT, and postmenopausal breast cancer risk in the Western New York Exposures and Breast Cancer case-control study. Cases (n = 616) were women with primary, incident, pathologically confirmed breast cancer. Randomly selected controls (n = 1,082) were frequency matched to cases on age and race. Genotype was assayed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) adjusted for potential confounders. CAT genotype alone was not associated with breast cancer risk. Ever use of HRT was associated with increased risk (OR, 1.39; 95% CI, 1.11-1.75). The increase with ever use was more pronounced among those with variant CT or TT CAT genotype (OR, 1.88; 95% CI, 1.29-2.75) than among those with CC (OR, 1.15; 95% CI, 0.86-1.54). Similarly, risk associated with >or=5 years of HRT use was greater among those with at least one variant T allele (OR, 2.32; 95% CI, 1.50-3.59). Increased risk was limited to estrogen receptor-positive tumors. Our findings suggest that CAT genotype modifies the effect of HRT use on breast cancer risk and that HRT may affect risk by affecting oxidative stress.
Quick
Sylvia K
SK
Department of Social, State University of New York at Buffalo, Buffalo, NY, USA. squick@buffalo.edu
Shields
Peter G
PG
Nie
Jing
J
Platek
Mary E
ME
McCann
Susan E
SE
Hutson
Alan D
AD
Trevisan
Maurizio
M
Vito
Dominica
D
Modali
Ramakrishna
R
Lehman
Teresa A
TA
Seddon
Mike
M
Edge
Stephen B
SB
Marian
Catalin
C
Muti
Paola
P
Freudenheim
Jo L
JL
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D002374:Catalase / Q000235:genetics*; D016009:Chi-Square Distribution; D015987:Effect Modifier, Epidemiologic; D015914:Estrogen Replacement Therapy; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D018384:Oxidative Stress; D011110:Polymorphism, Genetic; D017698:Postmenopause; D011960:Receptors, Estrogen / Q000235:genetics; D018570:Risk Assessment; D012307:Risk Factors
D011960:Receptors, Estrogen; D002374:Catalase