CYP17 genetic polymorphism, breast cancer, and breast cancer risk factors.
BACKGROUND
Findings from previous studies regarding the association between the CYP17 genotype and breast cancer are inconsistent. We investigated the role of the MspAI genetic polymorphism in the 5' region of CYP17 on risk of breast cancer and as a modifier of reproductive risk factors.


METHODS
Questionnaire and genotyping data were obtained from a population-based, case-control study of premenopausal (n = 182) and postmenopausal (n = 214) European-American Caucasian women in western New York. Cases and controls were frequency matched by age and by county of residence. Odds ratios and 95% confidence intervals were used to estimate relative risks.


RESULTS
The CYP17 genotype was not associated with breast cancer risk; however, controls with the A2/A2 genotype (associated with higher estrogens) had earlier menarche and earlier first full-term pregnancy. Premenopausal women with A1/A1 genotypes, but not with A2 alleles, were at significantly decreased risk with late age at menarche (odds ratio = 0.37, 95% confidence interval = 0.14-0.99), and at increased risk with late age at first full-term pregnancy (odds ratio = 4.30, 95% confidence interval = 1.46-12.67) and with use of oral contraceptives (odds ratio = 3.24, 95% confidence interval = 1.08-9.73). Associations were weaker among postmenopausal women.


CONCLUSIONS
These results suggest that the effects of factors that may alter breast cancer risk through a hormonal mechanism may be less important among premenopausal women with putative higher lifetime exposures to circulating estrogens related to the CYP17 A2 allele.
Ambrosone
Christine B
CB
Department of Epidemiology, Roswell Park Cancer Institute, Buffalo, New York, USA. christine.ambrosone@roswellpark.org
Moysich
Kirsten B
KB
Furberg
Helena
H
Freudenheim
Jo L
JL
Bowman
Elise D
ED
Ahmed
Sabrina
S
Graham
Saxon
S
Vena
John E
JE
Shields
Peter G
PG
D000328:Adult; D000368:Aged; D000483:Alleles; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017698:Postmenopause; D017697:Premenopause; D012307:Risk Factors; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics*
D013254:Steroid 17-alpha-Hydroxylase