Age-specific association of steroid hormone pathway gene polymorphisms with breast cancer risk.
BACKGROUND
Breast cancer (BC) is a complex disease, and the incidence rates for BC increase with age. Both environmental factors and genetics have an impact on the risk of BC. Although the effects of environmental factors may vary with age, it has been assumed generally that the penetrance of single nucleotide polymorphisms (SNPs) is constant throughout life. In the current study, the results demonstrated that certain SNPs exhibit BC risk associations that vary considerably with age.


METHODS
SNPs in 12 steroid hormone pathway genes were investigated for associations with BC risk in white women who were enrolled in an age-matched, case-control (1:2 for cases and controls, respectively) study that consisted of a discovery set (n = 5000 women) and an independent validation set (n = 1583 women).


RESULTS
Significant age-related trends were identified and confirmed for SNPs in 4 genes associated with BC risk. The cytosine/cytosine (C/C) genotype of cytochrome P450 XIB2 (CYP11B2) was associated with decreased risk at younger ages (ages 30-44 years) but an increased risk at older ages (ages 55-69 years). The homozygous cytosine-guanine (CG/CG) genotype of uridine phosphorylase glycosyltransferase 1A7 (UGT1A7) was associated with increased risk at younger ages but decreased risk at older ages. Associations in cytochrome P450 19 (CYP19) and progesterone receptor (PGR) were confined to middle age (ages 45-54 years).


CONCLUSIONS
The identification of age-specific genetic associations may have profound implications for future etiologic studies of BC and for the use of SNP genotyping to accurately predict the risk of BC in women.
Ralph
David A
DA
InterGenetics Incorporated, Oklahoma City, Oklahoma 73104, USA.
Zhao
Lue Ping
LP
Aston
Christopher E
CE
Manjeshwar
Sharmila
S
Pugh
Thomas W
TW
DeFreese
Daniele C
DC
Gramling
Bobby A
BA
Shimasaki
Craig D
CD
Jupe
Eldon R
ER
D000328:Adult; D000368:Aged; D000375:Aging / Q000235:genetics*; D001141:Aromatase / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics*; D002394:Catechol O-Methyltransferase / Q000235:genetics; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D014453:Glucuronosyltransferase / Q000235:genetics; D012739:Gonadal Steroid Hormones / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011980:Receptors, Progesterone / Q000235:genetics
D012739:Gonadal Steroid Hormones; D011980:Receptors, Progesterone; D001141:Aromatase; D019405:Cytochrome P-450 CYP11B2; D002394:Catechol O-Methyltransferase; D014453:Glucuronosyltransferase; C107611:UDP-glucuronosyltransferase, UGT1A7