Survival in operable non-small-cell lung cancer: role of p53 mutations, tobacco smoking and asbestos exposure

Our plain-English summary of Survival in operable non-small-cell lung cancer: role of p53 mutations, tobacco smoking and asbestos exposure, by T. Sioris, K. Husgafvel-Pursiainen, A. Karjalainen, et al (International Journal of Cancer, 2000).

The study

• Authors: T. Sioris, K. Husgafvel-Pursiainen, A. Karjalainen, S. Anttila, A. Kannio, J.A. Salo, V. Perhoniemi, L. Heikkilä, H. Vainio
• Journal: International Journal of Cancer
• Published: 2000;86(4):590-4
• Cited by: 28 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Validated markers are needed to identify operable lung cancer patients with poor prognosis. About one-half of non-small-cell lung cancers (NSCLCs) carry a mutation in the p53 tumor-suppressor gene. We examined 101 NSCLC patients for surgical stage, completeness of resection, tobacco smoking, asbestos exposure, age, gender and p53 gene mutations as prognostic factors after a follow-up period of 4 years. Cox's multivariate regression model was applied to quantify the associations with overall and cancer-related survival. Patients with a wild-type p53 gene had an overall 4-year survival of 43% and those with a mutated p53 gene, 35%. In squamous-cell carcinoma, stage and heavy smoking, defined as the median of pack-years smoked, had prognostic significance for overall survival. Only stage was associated with poor cancer-related survival. Asbestos exposure was not associated with overall survival or cancer-related survival in squamous-cell carcinoma or adenocarcinoma. In adenocarcinoma, p53 mutation, in addition to stage, emerged as a significant predictor of poor cancer-related survival.

Copyright 2000 Wiley-Liss, Inc.

In plain English

This study analysed 101 patients operated on with curative intent for non-small-cell lung cancer at Helsinki University Hospital, Finland, between August 1988 and December 1993. Analyses included only patients who survived at least 30 days after surgery: 59 with squamous-cell carcinoma and 42 with adenocarcinoma. The authors tested whether stage, completeness of surgery, smoking, past occupational asbestos exposure, age, sex and tumor p53 gene mutations predicted survival, with follow-up to the end of 1997. Asbestos exposure was judged from interviews, and patients with definite or probable exposure counted as exposed. Asbestos exposure was not associated with overall or lung-cancer-related survival in either tumor type. Overall 4-year survival was 40% (40/101). It was 43% (23/53) with a normal tumor p53 gene and 35% (17/48) with a mutation. Higher stage was linked to poorer survival. In adenocarcinoma, p53 mutation was significantly associated with poorer cancer-related survival in the full model, but only suggestively in a stepwise model. The authors noted the study was small with broad confidence intervals. They concluded it gave no clear answer on whether p53 mutation independently predicts poor prognosis.

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: Survival (prognostic) study of consecutive surgical lung cancer patients, analysed with Kaplan-Meier and Cox multivariate regression models
• Who was studied: 101 patients operated on with curative intent for primary lung cancer at the Helsinki University Hospital (Finland), August 1988 to December 1993. Analyses were limited to patients who survived at least 30 days after surgery: 59 with squamous-cell carcinoma and 42 with adenocarcinoma. Follow-up ran to December 31, 1997.
• Exposure: Past occupational asbestos exposure, assessed by personal interview with a standardized questionnaire and classified as definite, probable, possible or unlikely; definite or probable counted as exposed. No fiber types were specified. Smoking (pack-years) and p53 gene mutation status were also studied.
• Main results:
  • Asbestos exposure was not associated with overall survival or cancer-related survival in squamous-cell carcinoma or adenocarcinoma patients
  • Overall survival, squamous-cell carcinoma patients, exposed versus non-exposed to asbestos: OR 0.7 (95% CI 0.3 to 1.5), p = 0.37. For adenocarcinoma patients the corresponding figure was 1.0 (0.3 to 3.2), p = 0.98.
  • Lung cancer-related survival, exposed versus non-exposed to asbestos: OR 0.8 (0.3 to 2.0), p = 0.68, in squamous-cell carcinoma patients, and OR 0.8 (0.2 to 3.5), p = 0.82, in adenocarcinoma patients
  • 48 of the 101 patients (47%) had a p53 mutation in the tumor
  • Overall 4-year survival was 40% (40/101) for all patients
  • 4-year survival was 43% (23/53) in patients with a wild-type p53 gene
  • 4-year survival was 35% (17/48) in patients with a mutated p53 gene
  • In adenocarcinoma patients, p53 mutation was significantly associated with poorer cancer-related survival in the full Cox model: OR 3.5 (95% CI 1.1 to 11.5), p = 0.03. In the stepwise model it was only suggestive: OR 2.2 (0.9 to 5.6), p = 0.09.
  • In squamous-cell carcinoma patients, p53 mutation status was not related to survival
  • Stage was of prognostic significance for cancer-related survival in both histological groups
  • In squamous-cell carcinoma patients, heavy smoking (at or above the median pack-years) had suggestive, not statistically significant, prognostic value for overall survival: OR 1.9 (95% CI 0.9 to 3.8)
• The authors' conclusion: The authors concluded that their results suggest a significant association between p53 mutation and poor cancer-related survival in surgical adenocarcinoma patients. Because the study was small and the confidence intervals broad, they said it gave no clear answer on whether p53 mutation is an independent predictor of poor prognosis. They also stated that smoking and occupational asbestos exposure did not affect cancer-related survival in the multivariate model.
• Limitations the authors state:
  • Small study population with broad confidence intervals
  • Too few high-stage patients for meaningful analyses
  • No comparison with non-smokers was possible because there were too few
  • Lymph node status may have been understaged during surgery

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Lung Cancer, Asbestos Exposure, Prognosis, Carcinoma, Overall Survival, Adenocarcinoma.

Related studies

• Lung cancer and past occupational exposure to asbestos. Role of p53 and K-ras mutations — K. Husgafvel-Pursiainen, A. Karjalainen, et al. (1999)
• p53 and ras gene mutations in lung cancer: implications for smoking and occupational exposures — K. Husgafvel-Pursiainen, M. Ridanpää, et al. (1995)
• Loss of heterozygosity of chromosome 3p21 is associated with mutant TP53 and better patient survival in non-small-cell lung cancer — C.J. Marsit, M. Hasegawa, et al. (2004)
• Epidermal growth factor receptor mutations in 510 Finnish non--small-cell lung cancer patients — S. Mäki-Nevala, M. Rönty, et al. (2014)
• Hot spot mutations in Finnish non-small cell lung cancers — S. Mäki-Nevala, V.K. Sarhadi, et al. (2016)
• Interaction between smoking and asbestos in human lung adenocarcinoma: role of K-ras mutations — H. Vainio, K. Husgafvel-Pursiainen, et al. (1993)

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