Genetic polymorphisms and susceptibility to cancer development
T Sugimura1, R Inoue, H Ohgaki
1National Cancer Center Research Institute, Tokyo, Japan.
Pharmacogenetics
|January 1, 1995
Summary
Genetic factors influence cancer susceptibility. Researchers identified a single gene controlling resistance to stomach cancer in rats, offering insights into human gastric cancer genetics.
Area of Science:
- Genetics
- Cancer Biology
- Carcinogenesis
Background:
- Human cancer susceptibility varies due to genetic differences.
- Gastric cancer is prevalent in Japan, but its genetic underpinnings are poorly understood.
- Rat models are used to study genetic susceptibility to chemical-induced cancers.
Purpose of the Study:
- To investigate the genetic basis of susceptibility to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinogenesis in rats.
- To identify genes contributing to differences in cancer development.
- To explore the genetic background of breast cancer susceptibility in Japanese populations.
Main Methods:
- Carcinogenesis studies using different rat strains (Wistar, Buffalo, ACI) and their offspring (F1, F2).
- Analysis of O6-methylguanine adduct levels and cell proliferation in gastric mucosa.
- Linkage analyses of BRCA1 in Japanese families with breast cancer.
Main Results:
- A single autosomal dominant allele was suggested to regulate MNNG-induced stomach carcinogenesis resistance.
- O6-methylguanine adduct levels were similar, but cell proliferation was higher in sensitive ACI rats compared to resistant Buffalo rats.
- BRCA1 did not appear to be a major determinant of familial breast cancer in the studied Japanese population.
Conclusions:
- Genetic factors play a significant role in susceptibility to MNNG-induced gastric carcinogenesis.
- Further research, including chromosome mapping, is needed to identify the specific gene involved in rat gastric cancer susceptibility.
- BRCA1 may not be a primary driver of familial breast cancer in Japanese individuals.
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