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. 1996 May;104(Suppl 3):553–556. doi: 10.1289/ehp.96104s3553

Cigarette smoking and p53 mutations in lung cancer and bladder cancer.

K Husgafvel-Pursiainen 1, A Kannio 1
PMCID: PMC1469661  PMID: 8781382

Abstract

We report here a compilation of p53 mutation results from two smoking-related cancers, lung cancer and bladder cancer. The overall mutation frequencies reported for these two types of cancer were relatively similar--50% in lung cancer and 40% in bladder cancer. The compiled data from lung cancer and bladder cancer suggest an increasing proportion of patients with p53 mutations in nonsmokers, former smokers, and current smokers, in that order, in both cancer groups. Taken together, more than half (55% and 56% for lung cancer and bladder cancer, respectively) of the patients who continued smoking (CS), less than 40% (38% and 38%) of those who had stopped smoking before > or = 1 or > or = 5 years) clinical diagnosis (ES), and less than 30% (25% and 29%) of those who were nonsmokers (NS) had a p53 mutation. The differences seen in the mutation frequencies between the three smoking groups did not, however, reach statistical significance (lung cancer--CS vs ES: odds ratio [OR] = 2.0, 95% CI 0.7-5.4; CS vs NS: OR = 3.7, 95% CI 0.4-37; bladder cancer--CS vs ES: OR = 2.1, 95% CI 0.6-7.9; CS vs NS: OR = 3.1, 95% CI 0.7-13). Guanine to thymine transversions were the most common type in lung cancer followed by guanine to adenine transitions. In bladder cancer, on the contrary, G:C to A:T transitions at cytosine-guanine dinucleotide sites were the most frequently detected base substitutions. Analysis of the compiled p53 mutation data suggest that, in addition to lifetime cumulative exposure to cigarette smoke, also stopping smoking for years prior to clinical manifestation of the disease may affect the incidence of p53 mutations. The differences in the mutation profiles appear to support the view that the main genotoxic agents from cigarette smoke exposure may be different in bladder cancer as compared to lung cancer, as suggested previously by DNA adduct studies.

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Selected References

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  1. Alexandrov K., Rojas M., Geneste O., Castegnaro M., Camus A. M., Petruzzelli S., Giuntini C., Bartsch H. An improved fluorometric assay for dosimetry of benzo(a)pyrene diol-epoxide-DNA adducts in smokers' lung: comparisons with total bulky adducts and aryl hydrocarbon hydroxylase activity. Cancer Res. 1992 Nov 15;52(22):6248–6253. [PubMed] [Google Scholar]
  2. Bongiorno P. F., Whyte R. I., Lesser E. J., Moore J. H., Orringer M. B., Beer D. G. Alterations of K-ras, p53, and erbB-2/neu in human lung adenocarcinomas. J Thorac Cardiovasc Surg. 1994 Feb;107(2):590–595. [PubMed] [Google Scholar]
  3. Brash D. E., Rudolph J. A., Simon J. A., Lin A., McKenna G. J., Baden H. P., Halperin A. J., Pontén J. A role for sunlight in skin cancer: UV-induced p53 mutations in squamous cell carcinoma. Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10124–10128. doi: 10.1073/pnas.88.22.10124. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brennan J. A., Boyle J. O., Koch W. M., Goodman S. N., Hruban R. H., Eby Y. J., Couch M. J., Forastiere A. A., Sidransky D. Association between cigarette smoking and mutation of the p53 gene in squamous-cell carcinoma of the head and neck. N Engl J Med. 1995 Mar 16;332(11):712–717. doi: 10.1056/NEJM199503163321104. [DOI] [PubMed] [Google Scholar]
  5. Bressac B., Kew M., Wands J., Ozturk M. Selective G to T mutations of p53 gene in hepatocellular carcinoma from southern Africa. Nature. 1991 Apr 4;350(6317):429–431. doi: 10.1038/350429a0. [DOI] [PubMed] [Google Scholar]
  6. Doll R., Peto R., Wheatley K., Gray R., Sutherland I. Mortality in relation to smoking: 40 years' observations on male British doctors. BMJ. 1994 Oct 8;309(6959):901–911. doi: 10.1136/bmj.309.6959.901. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Esteve A., Sørlie T., Martel-Planche G., Hollstein M., Kusters I., Lewalter J., Vineis P., Stephan-Odenthal M., Montesano R. Screening for p53 gene mutations in archived tumors of workers occupationally exposed to carcinogens: examples from analysis of bladder tumors. J Occup Environ Med. 1995 Jan;37(1):59–68. doi: 10.1097/00043764-199501000-00009. [DOI] [PubMed] [Google Scholar]
  8. Harris C. C., Hollstein M. Clinical implications of the p53 tumor-suppressor gene. N Engl J Med. 1993 Oct 28;329(18):1318–1327. doi: 10.1056/NEJM199310283291807. [DOI] [PubMed] [Google Scholar]
  9. Hollstein M., Sidransky D., Vogelstein B., Harris C. C. p53 mutations in human cancers. Science. 1991 Jul 5;253(5015):49–53. doi: 10.1126/science.1905840. [DOI] [PubMed] [Google Scholar]
  10. Hsu I. C., Metcalf R. A., Sun T., Welsh J. A., Wang N. J., Harris C. C. Mutational hotspot in the p53 gene in human hepatocellular carcinomas. Nature. 1991 Apr 4;350(6317):427–428. doi: 10.1038/350427a0. [DOI] [PubMed] [Google Scholar]
  11. Husgafvel-Pursiainen K., Hackman P., Ridanpä M., Anttila S., Karjalainen A., Partanen T., Taikina-Aho O., Heikkilä L., Vainio H. K-ras mutations in human adenocarcinoma of the lung: association with smoking and occupational exposure to asbestos. Int J Cancer. 1993 Jan 21;53(2):250–256. doi: 10.1002/ijc.2910530213. [DOI] [PubMed] [Google Scholar]
  12. Kannio A., Ridanpä M., Koskinen H., Partanen T., Anttila S., Collan Y., Hietanen E., Vainio H., Husgafvel-Pursiainen K. A molecular and epidemiological study on bladder cancer: p53 mutations, tobacco smoking, and occupational exposure to asbestos. Cancer Epidemiol Biomarkers Prev. 1996 Jan;5(1):33–39. [PubMed] [Google Scholar]
  13. Karjalainen A., Anttila S., Heikkilä L., Karhunen P., Vainio H. Asbestos exposure among Finnish lung cancer patients: occupational history and fiber concentration in lung tissue. Am J Ind Med. 1993 Mar;23(3):461–471. doi: 10.1002/ajim.4700230309. [DOI] [PubMed] [Google Scholar]
  14. Puisieux A., Lim S., Groopman J., Ozturk M. Selective targeting of p53 gene mutational hotspots in human cancers by etiologically defined carcinogens. Cancer Res. 1991 Nov 15;51(22):6185–6189. [PubMed] [Google Scholar]
  15. Spruck C. H., 3rd, Rideout W. M., 3rd, Olumi A. F., Ohneseit P. F., Yang A. S., Tsai Y. C., Nichols P. W., Horn T., Hermann G. G., Steven K. Distinct pattern of p53 mutations in bladder cancer: relationship to tobacco usage. Cancer Res. 1993 Mar 1;53(5):1162–1166. [PubMed] [Google Scholar]
  16. Suzuki H., Takahashi T., Kuroishi T., Suyama M., Ariyoshi Y., Takahashi T., Ueda R. p53 mutations in non-small cell lung cancer in Japan: association between mutations and smoking. Cancer Res. 1992 Feb 1;52(3):734–736. [PubMed] [Google Scholar]
  17. Takeshima Y., Seyama T., Bennett W. P., Akiyama M., Tokuoka S., Inai K., Mabuchi K., Land C. E., Harris C. C. p53 mutations in lung cancers from non-smoking atomic-bomb survivors. Lancet. 1993 Dec 18;342(8886-8887):1520–1521. doi: 10.1016/s0140-6736(05)80087-x. [DOI] [PubMed] [Google Scholar]
  18. Talaska G., al-Juburi A. Z., Kadlubar F. F. Smoking related carcinogen-DNA adducts in biopsy samples of human urinary bladder: identification of N-(deoxyguanosin-8-yl)-4-aminobiphenyl as a major adduct. Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5350–5354. doi: 10.1073/pnas.88.12.5350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Uchida T., Wada C., Ishida H., Wang C., Egawa S., Yokoyama E., Kameya T., Koshiba K. p53 mutations and prognosis in bladder tumors. J Urol. 1995 Apr;153(4):1097–1104. [PubMed] [Google Scholar]
  20. Vogelstein B., Kinzler K. W. Carcinogens leave fingerprints. Nature. 1992 Jan 16;355(6357):209–210. doi: 10.1038/355209a0. [DOI] [PubMed] [Google Scholar]
  21. Warren W., Biggs P. J., el-Baz M., Ghoneim M. A., Stratton M. R., Venitt S. Mutations in the p53 gene in schistosomal bladder cancer: a study of 92 tumours from Egyptian patients and a comparison between mutational spectra from schistosomal and non-schistosomal urothelial tumours. Carcinogenesis. 1995 May;16(5):1181–1189. doi: 10.1093/carcin/16.5.1181. [DOI] [PubMed] [Google Scholar]
  22. Westra W. H., Offerhaus G. J., Goodman S. N., Slebos R. J., Polak M., Baas I. O., Rodenhuis S., Hruban R. H. Overexpression of the p53 tumor suppressor gene product in primary lung adenocarcinomas is associated with cigarette smoking. Am J Surg Pathol. 1993 Mar;17(3):213–220. doi: 10.1097/00000478-199303000-00001. [DOI] [PubMed] [Google Scholar]
  23. Williamson M. P., Elder P. A., Knowles M. A. The spectrum of TP53 mutations in bladder carcinoma. Genes Chromosomes Cancer. 1994 Feb;9(2):108–118. doi: 10.1002/gcc.2870090206. [DOI] [PubMed] [Google Scholar]
  24. Zhang Z. F., Sarkis A. S., Cordon-Cardo C., Dalbagni G., Melamed J., Aprikian A., Pollack D., Sheinfeld J., Herr H. W., Fair W. R. Tobacco smoking, occupation, and p53 nuclear overexpression in early stage bladder cancer. Cancer Epidemiol Biomarkers Prev. 1994 Jan-Feb;3(1):19–24. [PubMed] [Google Scholar]

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