Association between Cigarette Smoking and Mutation of the p53 Gene in Squamous-Cell Carcinoma of the Head and Neck

Brennan, Joseph; Boyle, Jay O.; Koch, Wayne M.; Goodman, Steven N.; Hruban, Ralph H.; Eby, Yolanda; Couch, Marion; Forastiere, Arlene A.; Sidransky, David

doi:10.1056/nejm199503163321104

Cited by 579 publications

(361 citation statements)

References 28 publications

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“…The biological mechanisms underpinning this association are not fully understood, but increased tumour hypoxia, resulting from increased carboxyhaemoglobin (the binding of carbon monoxide to haemoglobin) in smokers, is a likely explanation 43. In addition to this, it has been suggested that tobacco reduces the efficacy of radiotherapy through triggering a p53 mutation that could promote resistance to apoptosis 44. Smoking is also known to effect inflammatory responses45 and immune competence,46 which could increase the likelihood of adverse clinical outcomes.…”

Section: Discussionmentioning

confidence: 99%

Tobacco smoking and alcohol drinking at diagnosis of head and neck cancer and all‐cause mortality: Results from head and neck 5000, a prospective observational cohort of people with head and neck cancer

Beynon

Lang

Schimansky

et al. 2018

Intl Journal of Cancer

134

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Tobacco smoking and alcohol consumption are well‐established risk factors for head and neck cancer. The prognostic role of smoking and alcohol intake at diagnosis have been less well studied. We analysed 1,393 people prospectively enrolled into the Head and Neck 5000 study (oral cavity cancer, n=403; oropharyngeal cancer, n=660; laryngeal cancer, n=330) and followed up for a median of 3.5 years. The primary outcome was all‐cause mortality. We used Cox proportional hazard models to derive minimally adjusted (age and gender) and fully adjusted (age, gender, ethnicity, stage, comorbidity, body mass index, HPV status, treatment, education, deprivation index, income, marital status, and either smoking or alcohol use) mortality hazard ratios (HR) for the effects of smoking status and alcohol intake at diagnosis. Models were stratified by cancer site, stage and HPV status. The fully‐adjusted HR for current versus never‐smokers was 1.7 overall (95% confidence interval [CI] 1.1, 2.6). In stratified analyses, associations of smoking with mortality were observed for oropharyngeal and laryngeal cancers (fully adjusted HRs for current smokers: 1.8 (95% CI=0.9, 3.40 and 2.3 (95% CI=0.8, 6.4)). We found no evidence that people who drank hazardous to harmful amounts of alcohol at diagnosis had a higher mortality risk compared to non‐drinkers (HR=1.2 (95% CI=0.9, 1.6)). There was no strong evidence that HPV status or tumour stage modified the association of smoking with survival. Smoking status at the time of a head and neck cancer diagnosis influenced all‐cause mortality in models adjusted for important prognostic factors.

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Section: Discussionmentioning

confidence: 99%

Tobacco smoking and alcohol drinking at diagnosis of head and neck cancer and all‐cause mortality: Results from head and neck 5000, a prospective observational cohort of people with head and neck cancer

Beynon

Lang

Schimansky

et al. 2018

Intl Journal of Cancer

134

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“…Studies showing a positive association between TP53 mutation and tobacco smoke in patients with head and neck carcinoma are, however, more numerous e.g. [32-36] than studies with no association e.g. [38,58,59].…”

Section: Discussionmentioning

confidence: 99%

p53 in head and neck cancer: Functional consequences and environmental implications of TP53mutations

et al. 2010

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BackgroundAlthough TP53 mutations in human tumours generally have been extensively studied, the significance of p53 in the aetiology of head and neck cancers is still incompletely characterized. In recent years, considerable interest has been focused on mutant forms of p53, the abnormal protein product of TP53 alleles with missense mutation that often accumulate in cancer cells.MethodsWe compared the nature of TP53 mutations in primary 46 head and neck squamous cell carcinomas (HNSCC) analyzed by PCR-SSCP and sequencing, immunohistochemistry, and using structural information available at IARC p53 database.ResultsSequencing confirmed 36 TP53 mutations in 23 tumours of the 39 mutations in 26 tumours found by PCR-SSCP. Only half (17) putatively affect the function of p53 protein. Of these 8 were in the L2 domain, three affected the LSH motif and three the L3 domain. Three were in other domains. Codon 259 (GAC > GAA) which is a very rare mutation was found in 4 samples in our study. There were indications of p53 aberrations being associated with the combined effect of smoking, alcohol and work history. Patients with a negative family history of cancer had more often TP53 mutations than patients with a positive family history (71% vs. 46%).ConclusionsOur study contributes to the knowledge of cumulative chemical exposure and p53 aberrations in head and neck cancer, an area where literature is scarce.

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“…9,[15][16][17] In head and neck squamous cell carcinoma (SCC), a number of reports have documented overexpression of p53 protein 18 -21 and p53 gene mutation. 16,19,[22][23][24][25] However, conflicting results have been presented with regard to the correlation between prognosis and overexpression of p53. Some studies showed no correlation, 19,26 -28 whereas others showed a significant correlation between p53 expression and prognosis.…”

mentioning

confidence: 99%

Prognostic value of p53 mutations, bax, and spontaneous apoptosis in maxillary sinus squamous cell carcinoma

Bandoh

Hayashi

Kishibe

et al. 2002

Cancer

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Association between Cigarette Smoking and Mutation of the p53 Gene in Squamous-Cell Carcinoma of the Head and Neck

Cited by 579 publications

References 28 publications

Tobacco smoking and alcohol drinking at diagnosis of head and neck cancer and all‐cause mortality: Results from head and neck 5000, a prospective observational cohort of people with head and neck cancer

Tobacco smoking and alcohol drinking at diagnosis of head and neck cancer and all‐cause mortality: Results from head and neck 5000, a prospective observational cohort of people with head and neck cancer

p53 in head and neck cancer: Functional consequences and environmental implications of TP53mutations

Prognostic value of p53 mutations, bax, and spontaneous apoptosis in maxillary sinus squamous cell carcinoma

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