CYP3A4 Polymorphisms – Potential Risk Factors for Breast and Prostate Cancer: A Huge Review

Details

• Personal Author:
  Keshava C ; McCanlies EC ; Weston A
• Description:
  The steroid hydroxylase CYP3A4 is the most abundant P-450 enzyme in the human liver, and CYP3A enzymes metabolize more than 50% of prescription drugs. The CYP3A4 gene is expressed in the liver, gut, colon, prostate, and breast. Individual variation in CYP3A4 may play a role in breast and prostate carcinogenesis through modulation of sex hormone metabolite levels. Alternatively, CYP3A4 can metabolically activate exogenous carcinogens. CYP3A4 activity varies widely in humans, and more than 78 DNA sequence polymorphisms are known. These observations prompted the hypothesis that variant CYP3A4 may be involved in breast and prostate cancer. Two epidemiologic studies of breast cancer and five of prostate cancer examined CYP3A4 genotypes. A US study showed that inheritance of CYP3A4*1B correlates with early menarche, a breast cancer risk factor. However, an Australian breast cancer case-control study found no association with CYP3A4*1B. Two Scottish prospective studies showed CYP3A4*1B to be a risk factor for prostate cancer among men with benign prostatic hyperplasia. Three other studies were undertaken in the United States: two were case-only studies and the other was a case-sibling control study. Although results for African Americans were inconsistent, these studies suggested that CYP3A4*1B was associated with markers of advanced disease. These observations support the notion that development of robust, conventional molecular epidemiologic case-control studies to address these questions, including gene-gene and gene-environment interactions, will be timely. [Description provided by NIOSH]
• Subjects:
  Carcinogens Case Reports Energy Metabolism Epidemiology Genetics Neoplasms Occupational Health Risk Assessment Risk Factors Safety Urogenital Diseases Urogenital System

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• Keywords:
  Breast-cancer Cancer Carcinogenesis Carcinogenicity Case-studies Genes Genetic-factors Humans Metabolism Prostate-cancer Risk-analysis Risk-factors

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• ISSN:
  0002-9262
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  160
• Issue:
  9
• NIOSHTIC Number:
  nn:20025522
• Citation:
  Am J Epidemiol 2004 Nov; 160(9):825-841
• Contact Point Address:
  Dr. Ainsley Weston, National Institute for Occupational Safety and Health - CDC, 1095 Willowdale Road, MS-L3014, Morgantown, WV 26505-2888
• Email:
  agw8@cdc.gov
• Federal Fiscal Year:
  2005
• Peer Reviewed:
  True
• Source Full Name:
  American Journal of Epidemiology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:da1e1423faab98c5cf417ad7dd94598ed2b3d8fbf99b111e1ad93a679863724dc4dafe31f4fb29946272519fc1a57dc6669cb2495998e8f6392a64d3ddf76003
• Download URL:
  https://stacks.cdc.gov/view/cdc/196848/cdc_196848_DS1.pdf
• File Type:
  [PDF - 269.71 KB ]