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HuGE Cancer Epidemiology
HuGE Study
Masson, L. Sharp, S.C. Cotton and J. Little. Cytochrome P-450 1A1 Gene Polymorphisms and Risk of Breast Cancer: A HuGE Review. Am. J. Epidemiol. (15 May 2005) 161 (10): 901-915.
Category of HuGE Information
The types of information available from the article:
Prevalence of gene variant
Gene-disease association
Gene-environment interaction
Gene-gene interaction
Cytochrome P-450 (CYP) 1A1 plays a key role in phase I metabolism of polycyclic aromatic hydrocarbons and in estrogen metabolism. It is expressed predominantly in extrahepatic tissues, including the breast. Four CYP1A1 gene polymorphisms (3801T-C, Ile462Val, 3205T-C, and Thr461Asp) have been studied in relation to breast cancer. The 3801C variant is more common than the Val variant. Both variants occur more frequently in Asians than in White populations. The 3205T-C polymorphism has been observed in African-Americans only. Little data are available on the geographic/ethnic distribution of the Thr461Asp polymorphism. The functional significance of the polymorphisms is unclear. In 17 studies, no consistent association between breast cancer and CYP1A1 genotype was found. Meta-analysis found no significant risk for the genotypes 1) 3801C/C (relative risk (RR) = 0.97, 95% confidence interval (CI): 0.52, 1.80) or 3801T/C (RR = 0.91, 95% CI: 0.70, 1.19) versus 3801T/T, 2) Val/Val (RR = 1.04, 95% CI: 0.63, 1.74) or Ile/Val (RR = 0.92, 95% CI: 0.76, 1.10) versus Ile/Ile, or 3) Asp/Asp (RR = 0.95, 95% CI: 0.20, 4.49) or Thr/Asp (RR = 1.12, 95% CI: 0.87, 1.43) versus Thr/Thr. Future studies should explore possible interactions between CYP1A1 and sources of polycyclic aromatic hydrocarbons, markers of estrogen exposure, other lifestyle factors influencing hormonal levels, and other genes involved in polycyclic aromatic hydrocarbon metabolism or hormonal biosynthesis.
Gene:
Gene Name, Chromosome location, and gene product/function:
Cytochrome P-450 (CYP) 1A1 is a key enzyme in phase I bioactivation...
It contributes to aryl hydrocarbon hydroxylase activity, catalyzing the first step in the metabolism of a number of polycyclic aromatic hydrocarbons (PAHs), such as the tobacco carcinogen benzo[a]pyrene, to their ultimate DNA-binding forms. It is also involved in estrogen metabolism, catalyzing the hydroxylation of 17?-estradiol at the C-2 position.
The CYP1A1 gene, located at 15q22-q24, comprises seven exons and six introns and spans 5,810 base pairs. In humans, CYP1A1 is under the regulatory control of the aryl hydrocarbon receptor, a transcription factor that regulates gene expression.
CYP1A1 expression occurs predominantly in extrahepatic tissue. CYP1A1 messenger RNA has been detected in normal and cancerous breast tissue and can be induced in human-breast-derived cell lines.
Alleles: CYP1 family:
CYP1A1; CYP1A2; CYP1B1; CYP2 family: CYP2A6; CYP2A13; CYP2B6; CYP2C8; CYP2C9; CYP2C19; CYP2D6; CYP2E1; CYP2F1; CYP2J2; CYP2R1; CYP2S1; CYP2W1
CYP3 family:
CYP3A4; CYP3A5; CYP3A7; CYP3A43
CYP4 family:
CYP4A11; CYP4A22; CYP4B1; CYP4F2
CYP>4 families:
CYP5A1
CYP8A1
CYP19A1
CYP21A2
CYP26A1
OMIM #: 108330
Environmental Factors:
1. PAHs (polyaromatic hydrocarbons)
2. Tobacco smoke
3. Estrogen
4. Fried foods
5. Alcohol
6. PCBs (polychlorinated biphenols)
Health Outcomes:
1. Incidence of breast cancer risk in association with C-P450 mutations
2. Determine variants of C-P450 polymorphisms in specific ethnic populations
3. Determine gene-gene and gene-environment interactions for CP450 alleles and breast cancer.
Study design
This is a descriptive, cross-sectional study.
Assessment of environmental factors:
Environmental factor: Smoking
Exposure assessment and definition: genotype-smoking interactions light smokers (
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2008). Indeed better screening is necessary due to the number of false-negatives from women with precancerous lesions among the most frequent reasons of medical malpractice in the United States (Steben, M. et al. 2007). In the case of having a tissue sample to be tested, early stage cervical cancer can be differentiated from healthy cervical tissue by gene expression profile due to comparisons done with healthy and lymph node metastatic
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