Comparison of p53 mutations between adenocarcinoma and squamous cell carcinoma of the lung: unique spectra involving G to A transitions and G to T transversions in both histologic types

Gao, Wei; Mady, Hussam H.; Yu, Guo Ying; Siegfried, Jill M.; Luketich, James D.; Melhem, Mona F.; Keohavong, Phouthone

doi:10.1016/s0169-5002(03)00035-7

Cited by 44 publications

(54 citation statements)

References 46 publications

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“…For comparison, our previous studies of lung tumors showed a predominance of G:C-T:A transversion, followed by G:C-A:T transition, many of them occurred at hotspot codons 248 and 249 in lung adenocarcinomas from smokers, suggesting they were primarily induced by adducts caused by polycyclic aromatic hydrocarbons and aromatic amines in tobacco smoke. These mutations were different from those found in lung tumors from non-smokers that consisted predominantly of transitions and were scattered throughout exons 5 to 8 (41,42). Nevertheless, in bladder cancer it has been suggested that the G:C-A:T mutations may be induced by alkyl adducts, such as those caused by exposure to nitrosamines (54).…”

Section: ------------------------------------------------------------contrasting

confidence: 57%

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Genetic polymorphisms in the DNA repair genes XPD and XRCC1, p53 gene mutations and bladder cancer risk

Gao

Romkes²,

Zhong³

et al. 2010

Oncol Rep

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Abstract. Previous studies have suggested that certain genetic polymorphisms, specifically the Xeroderma pigmentosum group D (XPD) gene codon 751 and the X-ray repair crosscomplementing group 1 (XRCC1) gene codon 399 polymorphisms, were associated with an increased risk of lung cancer, and, in some studies, with a greater risk for mutations in the p53 tumor suppressor gene in lung tumors. To evaluate whether these gene polymorphisms may be associated with an increased risk for bladder cancer or in association with p53 mutation status in bladder tumors, we screened for polymorphisms at XPD codons 751 and XRCC1 codon 399 in DNA isolated from blood of 194 bladder cancer patients and 313 healthy controls and for mutations in exons 4 to 8 of the p53 gene in bladder tumor DNA from 174 bladder cancer patients. There was a significantly higher prevalence of the XPD 751 Gln allele among the bladder cancer group, compared with the control group. No association was found between bladder cancer risk and the XRCC1 399 polymorphism. p53 mutations were found in 20.1% (35/174) patients. There was no difference in p53 mutation status among individuals with different genotypes. These results suggest that individuals who have the XPD 751 Gln allele may be at an increased risk for bladder cancer, although this may not lead to an increased risk for mutations in the p53 gene.

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Section: ------------------------------------------------------------contrasting

confidence: 57%

“…Mutations in exons 4-8 of the p53 gene from 174 patients were analyzed using PCR+SSCP as described previously (41,42). Each mutant allele appearing on the gel was isolated and further characterized by sequencing, using an ABI PRISM 377 automatic sequencer.…”

Section: Analysis Of P53 Mutations and Xpd And Xrcc1 Genotypingmentioning

confidence: 99%

Genetic polymorphisms in the DNA repair genes XPD and XRCC1, p53 gene mutations and bladder cancer risk

Gao

Romkes²,

Zhong³

et al. 2010

Oncol Rep

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“…This result strongly suggests that XPC inactivation may contribute to the occurrence of p53 mutation in lung cancer cells. Among lung cancer patients, p53 mutation frequency in lung cancer is generally higher in smokers than in nonsmokers (Gao et al, 2003;Toyooka et al, 2003b;Chang et al, 2005;Le Calvez et al, 2005). However, there were no differences in the frequency of lung cancer patients presenting with p53 mutations between smokers and nonsmokers in the Taiwanese population used in this study; 34 of 94 (36%) nonsmokers versus 25 of 64 (39%) smokers with p53 mutation (P ¼ 0.712).…”

Section: Discussionmentioning

confidence: 58%

Xeroderma pigmentosum group C gene expression is predominantly regulated by promoter hypermethylation and contributes to p53 mutation in lung cancers

Chang

Cheng

et al. 2007

Oncogene

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Reduced DNA repair capability is associated with developing lung cancer, especially in nonsmokers. XPC participates in the initial recognition of DNA damage during the DNA nucleotide excision repair process. We hypothesize that inactivation of XPC by promoter hypermethylation may play an important role in the reduction of DNA repair capability to cause p53 mutation during lung carcinogenesis. In this report we demonstrate that hypermethylation of 17 CpG islands between À175 and À1 of the XPC promoter correlates very well with XPC expression levels in eight lung cancer cell lines. When cells with hypermethylated XPC promoters were treated with the demethylating agent 5-aza-2 0 -deoxycytidine, XPC expression was de-repressed. Interestingly, XPC hypermethylation was found in 4 of 5 (80%) lung cancer cell lines harbored p53 mutation, but not observed in two lung cancer cells which had a wild-type p53 gene. Among the analysis of the hypermethylation status of 158 lung tumors, XPC hypermethylation is more common in nonsmokers (39 of 94, 41%) than in smokers (14 of 64, 22%; P ¼ 0.010). Additionally, XPC hypermethylation is more often with G-T or G-C mutations in the p53 gene. To verify whether XPC inactivation is involved in the occurrence of p53 mutation, XPC gene of A549 cells was knockdown by a small interference RNA and then XPC-inactivated cells were treated with benzo[a]pynrene for different passages. Surprisingly, G-T mutation in p53 gene at codon 215 was indeed detected in XPCinactivated A549 cells of passages 15 and confirmed by loss of transcription activity of mdm2. These results show that hypermethylation of the XPC promoter may play a crucial role in XPC inactivation, which may partly contribute to the occurrence of p53 mutations during lung tumorigenesis, especially nonsmokers.

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“…It is possible that activator protein-1 mutant frequencies are different between different histologic subtypes of lung cancer, which may induce the differential association between MMP-1 polymorphism and lung cancer risk by histologic subtypes. An alternative explanation is that squamous cell carcinoma tumor tissues have been found to have higher rates of p53 mutations than adenocarcinoma tissues (22). MMP-1 is a target of the p53 protein, and wild-type p53 can exert a strong inhibitory effect on the human MMP-1 promoter by disrupting communications between the transactivator À72AP-1 and the basal transcriptional complex, whereas p53 mutants lose such repressive activity (23,24).…”

Section: Discussionmentioning

confidence: 99%

Matrix Metalloproteinase-1 Promoter Polymorphism and Lung Cancer Risk

Li¹,

Zhou²,

Park

et al. 2005

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Extracellular matrix-degrading matrix metalloproteinase-1 (MMP-1) is an interstitial collagenase that degrades the interstitial types I, II, and III collagens, and overexpression of MMP-1 is associated with cancer development and cellular invasion. The 2G allele of the MMP-1 À1607 1G/2G polymorphism is associated with enhanced transcriptional activity. We investigated the association between the MMP-1 1G/2G polymorphism and lung cancer risk in 1,752 Caucasian lung cancer patients and 1,363 healthy controls. There were no overall associations between the MMP-1 genotypes and risk of lung cancer, with the adjusted odds ratios of 1.15 [95% confidence interval (CI), 0.94-1.40] for the 1G/2G genotype and 1.14 (95% CI, 0.90-1.45) for the 2G/2G genotype, when versus the 1G/1G genotype. Stratified analyses suggested higher lung cancer risk for the 2G allele in never-smokers and males, with the adjusted odds ratios of 1.67 (95% CI, 1.02-2.76; 1G/2G) and 1.50 (95% CI, 0.86-2.62; 2G/2G) in never-smokers; and 1.30 (95% CI, 1.00-1.75; 1G/2G) and 1.23 (95% CI, 0.88-1.73; 2G/2G) in males, respectively. In conclusion, genotypes containing the 2G allele of the MMP-1 polymorphism are associated with higher risk of lung cancer in never-smokers and in males. (Cancer Epidemiol Biomarkers Prev 2005;14(3):567 -70)

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Comparison of p53 mutations between adenocarcinoma and squamous cell carcinoma of the lung: unique spectra involving G to A transitions and G to T transversions in both histologic types

Cited by 44 publications

References 46 publications

Genetic polymorphisms in the DNA repair genes XPD and XRCC1, p53 gene mutations and bladder cancer risk

Genetic polymorphisms in the DNA repair genes XPD and XRCC1, p53 gene mutations and bladder cancer risk

Xeroderma pigmentosum group C gene expression is predominantly regulated by promoter hypermethylation and contributes to p53 mutation in lung cancers

Matrix Metalloproteinase-1 Promoter Polymorphism and Lung Cancer Risk

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