Journal Article

The initiation of breast and prostate cancer

Philip L. Grover and Francis L. Martin

in Carcinogenesis

Volume 23, issue 7, pages 1095-1102
Published in print July 2002 | ISSN: 0143-3334
Published online July 2002 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/23.7.1095
The initiation of breast and prostate cancer

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The agents responsible for the initiation of human mammary and prostatic cancers remain unidentified. Population migration studies on breast and prostate cancer risk have revealed that incidence rates in migrants from low-risk to high-risk ‘Westernized’ countries rise over time to match those of the host populations. The parallels suggest that the two diseases may share a common aetiology, with changes in diet, rather than in environment, being responsible for the migration-related increases in cancer incidence. Genotoxins, such as polycyclic aromatic hydrocarbons and heterocyclic aromatic amines, are formed when foodstuffs are cooked at elevated temperatures and can be extracted with solvents: other genotoxins may only be released from cooked proteins when digestion occurs in the gastrointestinal tract. Human mammary and prostatic epithelial cells are known to be capable of metabolically activating members of different classes of chemical carcinogens to DNA-reactive species and, in rodents, five out of six mammary carcinogens can also induce prostatic neoplasms. Genotoxins have been detected in some 40% of breast lipid and milk samples donated by UK-resident women but the agents, currently thought to be of dietary origin, have not been characterized or identified as yet. Reduction mammoplasty and lactation both reduce breast cancer risk and the reduction is proportional either to the amount of tissue removed or to the total duration of lactation. As DNA damage has been detected in otherwise untreated mammary epithelial cells isolated both from breast tissue and from breast milk, we have proposed that reduction mammoplasty and lactation reduce risk through a common mechanism, i.e. the loss of pre-malignant cells. Further research, perhaps aimed particularly at the characterization of all the carcinogens formed when different dietary components are cooked in different ways, should succeed in identifying the agents that initiate breast and prostate cancer.

Keywords: B[a]P, benzo[a]pyrene; DMBA, 7, 12-dimethylbenz[a]anthracene; HAAs; heterocyclic aromatic amines; Trp-P-1, 3-amino-1, 4-dimethyl-5H-pyrido[4,3-b]-indole; Trp-P-2, 3-amino-1-methyl-5H-pyrido[4,3-b]-indole; IQ, 2-amino-3-methylimidazo[4,5-f]quinoline; MNU, N-methyl-N-nitrosourea; PAHs, polycyclic aromatic hydrocarbons; PhIP, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine.

Journal Article.  6864 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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