Population-based case-control study of AhR (aryl hydrocarbon receptor) and CYP1A2 polymorphisms and breast cancer risk.
The aryl hydrocarbon receptor (AhR) is a key regulator of the transcriptional expression for the cytochrome P450 1 (CYP1) genes. CYP1A2 is one of the major CYP1 enzymes that catalyse 2-hydroxylation of estrogen, a hormone that plays a critical role in the etiology of breast cancer. In this study, we investigated whether two common polymorphisms in these two genes, CYP1A2*1F and AhR Lys554Arg, were associated with breast cancer risk in 1090 cases and 1183 controls, a subset of the population-based case-control study, the Shanghai Breast Cancer Study. Caffeine tests were performed in vivo in a subset of 236 study subjects to investigate the relationship of these two polymorphisms with CYP1A2 activity. For the AhR gene, the A (Lys) allele was associated with a decreased risk of breast cancer. Using the genotype GG as reference, odds ratios of 0.82 [95% confidence interval (CI)=0.69-0.99] for the AG genotype and 0.76 (95% CI=0.58-1.01) for the AA genotype (P for trend=0.018) were obtained. However, no association was observed between CYP1A2 genotypes and breast cancer risk, although the CYP1A2*1F polymorphism was found to be related to CYP1A2 activity. The geometric mean values for the caffeine metabolites ratio were 2.90, 2.30, and 1.95 for CC, AC, and AA genotypes, respectively (P for trend=0.024). In conclusion, the results from our study suggest that the AhR Lys554Arg polymorphism may be a genetic susceptibility factor for breast cancer, whereas CYP1A2*1F, which is a potentially functional single nucleotide polymorphism, may not be related to breast cancer risk.
Department of Medicine and Vanderbilt-Ingram Cancer Center, Vanderbilt University, 1161 21st Avenue South, Nashville, TN 37232, USA.
Ji-Rong
JR
Long
Kathleen M
KM
Egan
Lisa
L
Dunning
Xiao-Ou
XO
Shu
Qiuyin
Q
Cai
Hui
H
Cai
Qi
Q
Dai
Jordan
J
Holtzman
Yu-Tang
YT
Gao
Wei
W
Zheng
D000328:Adult; D000483:Alleles; D001943:Breast Neoplasms / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D016001:Confidence Intervals; D019388:Cytochrome P-450 CYP1A2 / Q000032:analysis / Q000235:genetics*; D005260:Female; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics*; D012042:Registries / Q000706:statistics & numerical data; D012307:Risk Factors; D011795:Surveys and Questionnaires; D014505:Urban Population
D018336:Receptors, Aryl Hydrocarbon; D019388:Cytochrome P-450 CYP1A2