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Population-based case-control study of AhR (aryl hydrocarbon receptor) and CYP1A2 polymorphisms and breast cancer risk.
Pharmacogenet Genomics. 2006 Apr; 16(4):237-43.PG

Abstract

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.

Authors+Show Affiliations

Department of Medicine and Vanderbilt-Ingram Cancer Center, Vanderbilt University, 1161 21st Avenue South, Nashville, TN 37232, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

16538170

Citation

Long, Ji-Rong, et al. "Population-based Case-control Study of AhR (aryl Hydrocarbon Receptor) and CYP1A2 Polymorphisms and Breast Cancer Risk." Pharmacogenetics and Genomics, vol. 16, no. 4, 2006, pp. 237-43.
Long JR, Egan KM, Dunning L, et al. Population-based case-control study of AhR (aryl hydrocarbon receptor) and CYP1A2 polymorphisms and breast cancer risk. Pharmacogenet Genomics. 2006;16(4):237-43.
Long, J. R., Egan, K. M., Dunning, L., Shu, X. O., Cai, Q., Cai, H., Dai, Q., Holtzman, J., Gao, Y. T., & Zheng, W. (2006). Population-based case-control study of AhR (aryl hydrocarbon receptor) and CYP1A2 polymorphisms and breast cancer risk. Pharmacogenetics and Genomics, 16(4), 237-43.
Long JR, et al. Population-based Case-control Study of AhR (aryl Hydrocarbon Receptor) and CYP1A2 Polymorphisms and Breast Cancer Risk. Pharmacogenet Genomics. 2006;16(4):237-43. PubMed PMID: 16538170.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Population-based case-control study of AhR (aryl hydrocarbon receptor) and CYP1A2 polymorphisms and breast cancer risk. AU - Long,Ji-Rong, AU - Egan,Kathleen M, AU - Dunning,Lisa, AU - Shu,Xiao-Ou, AU - Cai,Qiuyin, AU - Cai,Hui, AU - Dai,Qi, AU - Holtzman,Jordan, AU - Gao,Yu-Tang, AU - Zheng,Wei, PY - 2006/3/16/pubmed PY - 2006/7/28/medline PY - 2006/3/16/entrez SP - 237 EP - 43 JF - Pharmacogenetics and genomics JO - Pharmacogenet Genomics VL - 16 IS - 4 N2 - 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. SN - 1744-6872 UR - https://www.unboundmedicine.com/medline/citation/16538170/Population_based_case_control_study_of_AhR__aryl_hydrocarbon_receptor__and_CYP1A2_polymorphisms_and_breast_cancer_risk_ L2 - https://doi.org/10.1097/01.fpc.0000189803.34339.ed DB - PRIME DP - Unbound Medicine ER -