Heavy smokers have higher bcl-2 mutation frequency and risk for lymphoma than non-smokers
- Univ. of Southern California, Los Angeles, CA (United States)
Early detection of cells carrying somatic mutations at oncogenic loci could prove useful for identifying individuals at high risk for cancer and permit intervention prior to the onset of clinically recognizable disease. We have determined the frequency of rare t(14;18)(q32;q21) translocations at the bcl-2 proto-oncogene locus in the peripheral blood of 85 smokers and 35 nonsmokers using a sensitive nested PCR assay. The identical translocation occurs in 85% of follicular lymphoma tumors, and about 50% of all non-Hodgkin`s Lymphoma. Smokers with the highest exposure had a 3.6-fold higher mutation frequency relative to the nonsmokers. Logistic regression analysis showed that of the variables tested (age, race, sex, current smoking, years of smoking, and pack-years), the cumulative smoking measure (pack-years) was the best predictor of t(14;18) frequency (p=0.004). These observations are consistent with two recent epidemiological studies showing 2.3-fold and 3.8-fold increased risk for Non-Hodgkins lymphoma among heavy smokers. The results support the hypothesis that smokers have an increased burden of lymphocytes bearing bcl-2 mutations which raises their individual risk for future lymphoid tumors. We speculate that the increased frequency of oncogenic translocations in smokers may result either from the mutagenic or antigenic activity of cigarette smoke.
- OSTI ID:
- 133537
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; TRN: 95:005313-0265
- Journal Information:
- American Journal of Human Genetics, Vol. 55, Issue Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
- Country of Publication:
- United States
- Language:
- English
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BASIC STUDIES
ONCOGENES
GENETIC EFFECTS
GENE MUTATIONS
MUTATION FREQUENCY
HUMAN CHROMOSOME 14
GENETIC MAPPING
CHROMOSOMAL ABERRATIONS
HUMAN CHROMOSOME 18
LYMPHOMAS
EPIDEMIOLOGY
RISK ASSESSMENT
ANIMAL CELLS
SOMATIC MUTATIONS
PATIENTS
POLYMERASE CHAIN REACTION
TOBACCO SMOKES
REGRESSION ANALYSIS