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The p53 codon 72 polymorphism and lung cancer risk.
Cancer Epidemiol Biomarkers Prev. 2000 Oct; 9(10):1037-42.CE

Abstract

The p53 tumor suppressor gene frequently is mutated in many forms of human carcinomas. A common polymorphism occurs at codon 72 of exon 4, with two alleles encoding either arginine (CGC) or proline (CCC). This p53 polymorphism reportedly is associated with lung cancer susceptibility. However, not all investigations have been consistent, and this hypothesized association remains controversial. We tested the hypothesis that the Pro/Pro genotype is associated with increased lung cancer risk in a large case-control study of lung cancer that included 482 cases and 510 controls from the Massachusetts General Hospital in Boston, Massachusetts. DNA from peripheral blood samples was examined by PCR-RFLP. Pro/Pro homozygotes were found more frequently in adenocarcinomas (cases, 16.4%; controls, 12.0%; P = 0.03). The prevalence of the Pro/Pro homozygous genotype increased in frequency with increasing pack-years of smoking. The combined susceptible genotype homozygous Pro/Pro and heterozygous Arg/Pro was associated with a 1.45-fold higher risk of adenocarcinoma compared with Arg/Arg genotype (95% confidence interval = 1.01-2.06; P = 0.04) after adjustment for relevant variables. Lung adenocarcinoma risk increased with the presence of one or both variant alleles across smoking strata. In addition, at each level of smoking (except nonsmoker and light smoker), the risk associated with smoking was higher for the population with the combined variant (Arg/Pro + Pro/Pro) genotype. The risk for the combined genotype was associated with tobacco exposure status. In conclusion, the codon 72 germ-line polymorphism (Arg/Pro) of the common tumor suppressor gene p53 contributes to heritable susceptibility for smoke-induced lung adenocarcinoma. The modifications by p53 polymorphism and pack-years resulted in an increased risk of the susceptible genotype to lung adenocarcinoma. The p53 gene may modulate the response to environment carcinogens and thereby affect the risk of developing lung adenocarcinoma.

Authors+Show Affiliations

Department of Environmental Health (Occupational Health Program), Harvard School of Public Health, Boston, Massachusetts 02115, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11045785

Citation

Fan, R, et al. "The P53 Codon 72 Polymorphism and Lung Cancer Risk." Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored By the American Society of Preventive Oncology, vol. 9, no. 10, 2000, pp. 1037-42.
Fan R, Wu MT, Miller D, et al. The p53 codon 72 polymorphism and lung cancer risk. Cancer Epidemiol Biomarkers Prev. 2000;9(10):1037-42.
Fan, R., Wu, M. T., Miller, D., Wain, J. C., Kelsey, K. T., Wiencke, J. K., & Christiani, D. C. (2000). The p53 codon 72 polymorphism and lung cancer risk. Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored By the American Society of Preventive Oncology, 9(10), 1037-42.
Fan R, et al. The P53 Codon 72 Polymorphism and Lung Cancer Risk. Cancer Epidemiol Biomarkers Prev. 2000;9(10):1037-42. PubMed PMID: 11045785.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The p53 codon 72 polymorphism and lung cancer risk. AU - Fan,R, AU - Wu,M T, AU - Miller,D, AU - Wain,J C, AU - Kelsey,K T, AU - Wiencke,J K, AU - Christiani,D C, PY - 2000/10/25/pubmed PY - 2001/3/3/medline PY - 2000/10/25/entrez SP - 1037 EP - 42 JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology JO - Cancer Epidemiol Biomarkers Prev VL - 9 IS - 10 N2 - The p53 tumor suppressor gene frequently is mutated in many forms of human carcinomas. A common polymorphism occurs at codon 72 of exon 4, with two alleles encoding either arginine (CGC) or proline (CCC). This p53 polymorphism reportedly is associated with lung cancer susceptibility. However, not all investigations have been consistent, and this hypothesized association remains controversial. We tested the hypothesis that the Pro/Pro genotype is associated with increased lung cancer risk in a large case-control study of lung cancer that included 482 cases and 510 controls from the Massachusetts General Hospital in Boston, Massachusetts. DNA from peripheral blood samples was examined by PCR-RFLP. Pro/Pro homozygotes were found more frequently in adenocarcinomas (cases, 16.4%; controls, 12.0%; P = 0.03). The prevalence of the Pro/Pro homozygous genotype increased in frequency with increasing pack-years of smoking. The combined susceptible genotype homozygous Pro/Pro and heterozygous Arg/Pro was associated with a 1.45-fold higher risk of adenocarcinoma compared with Arg/Arg genotype (95% confidence interval = 1.01-2.06; P = 0.04) after adjustment for relevant variables. Lung adenocarcinoma risk increased with the presence of one or both variant alleles across smoking strata. In addition, at each level of smoking (except nonsmoker and light smoker), the risk associated with smoking was higher for the population with the combined variant (Arg/Pro + Pro/Pro) genotype. The risk for the combined genotype was associated with tobacco exposure status. In conclusion, the codon 72 germ-line polymorphism (Arg/Pro) of the common tumor suppressor gene p53 contributes to heritable susceptibility for smoke-induced lung adenocarcinoma. The modifications by p53 polymorphism and pack-years resulted in an increased risk of the susceptible genotype to lung adenocarcinoma. The p53 gene may modulate the response to environment carcinogens and thereby affect the risk of developing lung adenocarcinoma. SN - 1055-9965 UR - https://www.unboundmedicine.com/medline/citation/11045785/The_p53_codon_72_polymorphism_and_lung_cancer_risk_ L2 - http://cebp.aacrjournals.org/cgi/pmidlookup?view=long&pmid=11045785 DB - PRIME DP - Unbound Medicine ER -