Environmental factors as regulators and effectors of multistep carcinogenesis

Our plain-English summary of Environmental factors as regulators and effectors of multistep carcinogenesis, by T. Minamoto, M. Mai, Z. Ronai (Carcinogenesis, 1999).

The study

• Authors: T. Minamoto, M. Mai, Z. Ronai
• Journal: Carcinogenesis
• Published: 1999;20(4):519-27
• Type of article: Review
• Cited by: 72 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

This review highlights current knowledge of environmental factors in carcinogenesis and their cellular targets. The hypothesis that environmental factors influence carcinogenesis is widely supported by both epidemiological and experimental studies. The fact that only a small fraction of cancers can be attributed to germline mutations in cancer-related genes further buttresses the importance of environmental factors in carcinogenesis. Furthermore, penetrance of germline mutations may be modified by either environmental or other genetic factors. Examples of environmental factors that have been associated with increased cancer risk in the human population include chemical and physical mutagens (e.g. cigarette smoke, heterocyclic amines, asbestos and UV irradiation), infection by certain viral or bacterial pathogens, and dietary non-genotoxic constituents (e.g. macro- and micronutrients). Among molecular targets of environmental influences on carcinogenesis are somatic mutation (genetic change) and aberrant DNA methylation (epigenetic change) at the genomic level and post-translational modifications at the protein level. At both levels, changes elicited affect either the stability or the activity of key regulatory proteins, including oncoproteins and tumor suppressor proteins. Together, via multiple genetic and epigenetic lesions, environmental factors modulate important changes in the pathway of cellular carcinogenesis.

In plain English

This 1999 article in Carcinogenesis was a review. The authors summarized earlier research and reported no new study. The review covered evidence that factors from outside the body influence cancer development. This included other studies' reports of cancer-rate differences between Japanese and Western populations and of 'signature mutations' linking agents such as UV light, aflatoxin and vinyl chloride to particular gene changes. It then described how chemical and physical carcinogens, diet, bacterial and viral infections, and inherited (germline) mutations and gene variants may affect cancer development. In the body of the review, asbestos was named only once, alongside UV irradiation and radon, as an example of a physical carcinogen. A table cited an earlier study whose title refers to apoptosis (cell death) caused by asbestos and hydrogen peroxide, but the table described only the hydrogen peroxide result. The review gave no asbestos fiber types, no asbestos-related diseases, no exposure data and no findings specific to asbestos. The authors concluded that the emerging concept is that environmental factors combined with individual susceptibility determine a person's likelihood of developing a tumor, and its type and incidence.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of published literature; no original data
• Who was studied: No study population. The review discussed published epidemiological and experimental studies on environmental factors in cancer: chemical and physical carcinogens, diet, bacterial and viral infection, and endogenous factors (germline mutations, gene polymorphism).
• Exposure: Many environmental factors were discussed. Asbestos was named in the body text only as one example of a physical carcinogen, alongside UV irradiation and radon, with no fiber type, product, job or dose given.
• Main results:
  • The review cited other studies reporting that the rate of gastric cancer in Japan is as much as six times higher than in Western populations.
  • The review described 'signature mutations' that earlier studies had reported. These link specific agents (UV, aflatoxin B1, tobacco-derived carcinogens, vinyl chloride) to specific patterns of change in the p53 gene.
  • The authors divided chemical and physical carcinogens into two groups: DNA-damaging agents that cause permanent somatic mutations, and agents that alter cell signaling pathways, causing transient changes in proteins.
  • The review stated that germline mutations in more than 20 different genes had been reported as hereditary traits increasing cancer susceptibility.
  • Table I cited reference 67, an earlier study whose title refers to apoptosis by asbestos and H2O2 (hydrogen peroxide). The table entry described only the hydrogen peroxide finding.
• The authors' conclusion: The authors concluded that the emerging concept is that environmental factors acting together with individual susceptibility determine a person's likelihood of developing a tumor, and the tumor's type and incidence.

Topics

Medical terms in this study, explained in our Lexicon: Carcinogenesis, Germline Mutation, Somatic Mutation.

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