Impact of Environmental Tobacco Smoke on the Incidence of Mutations in Epidermal Growth Factor Receptor Gene in Never-Smoker Patients With Non–Small-Cell Lung Cancer

Lee, Young Joo; Cho, Byoung Chul; Jee, Sun Ha; Moon, Jin Wook; Kim, Se Kyu; Chang, Joon; Chung, Kwansoo; Park, In Kyu; Choi, Sung Ho; Kim, Joo Hang

doi:10.1200/jco.2009.24.5480

Cited by 72 publications

(60 citation statements)

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“…17,18 All of our patients with EGFR mutation (n= 3) had adenocarcinoma in parallel to the literature and two of them had no smoking history. 16,17,19,20 It was reported that passive smoking ('environmental tobacco smoke exposure') might have been inversely related to EGFR mutations, even in the people who had never smoked actively. 20 It was not easy to document 'real' passive smokers among non-smokers in our study since the criteria for second-hand smoke 'intensity' are not so clear almost in the literature.…”

Section: Discussionmentioning

confidence: 99%

“…16,17,19,20 It was reported that passive smoking ('environmental tobacco smoke exposure') might have been inversely related to EGFR mutations, even in the people who had never smoked actively. 20 It was not easy to document 'real' passive smokers among non-smokers in our study since the criteria for second-hand smoke 'intensity' are not so clear almost in the literature. So, its effect on EGFR mutation rates could not have been clarified.…”

Section: Discussionmentioning

confidence: 99%

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The Relationship Between Common EGFR, BRAF, KRAS Mutations and Prognosis in Advanced Stage Non-Small Cell Lung Cancer with Response to the Treatment in Turkey.

Doğan¹

2014

UHOD

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The aim of the study was to evaluate EGFR (exon 19 deletion, exon 21 L858R point mutation), KRAS and braf mutation rates besides their relationship with survival and response to the treatment in non small cell lung cancer (NSCLC). We evaluated 513 NSCLC patients followed-up between January 2004 and November 2009 according to our registration data, retrospectively. Only 42 advanced stage NSCLC patients had enough tumor tissue material in paraffin blocks for all mutation analysis. The patients were evaluated retrospectively for clinicopathological features, EGFR, KRAS and BRAF mutations, erlotinib treatment, time to progression (TTP) and overall survival (OS).Mutation rates were as 7.14% (two patients) for EGFR exon 19 deletion; 4.76% (one patient)for KRAS codon 61 deletion and 2.38% for BRAF V600E mutation. They had neither EGFR exon 21 point mutation nor different mutations together. Median follow-up was 26 months (5-83) for all patients. It was 43 months (23-83) for the patients who had erlotinib and 23 months (5-61) for those who did not. Ten (23.8%) patients had erlotinib. There was significant survival difference between the patients taking erlotinib and the others (28 ± 3 months versus 15 ± 4 months, p= 0.05). TTP and OS were longer in the patients who had mutations, however the difference was not significant (p= 0.119 and p= 0.06). To our knowledge, this is the first study evaluating EGFR, KRAS and BRAF mutations in advanced stage NSCLC in Turkey .

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Relationship Between Common EGFR, BRAF, KRAS Mutations and Prognosis in Advanced Stage Non-Small Cell Lung Cancer with Response to the Treatment in Turkey.

Doğan¹

2014

UHOD

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“…1 However, approximately 25% of lung cancers occur in lifelong never-smokers, and the proportion of neversmokers with lung cancer has been increasing over time. [1][2][3][4] The development of lung cancer in never-smokers (LCINS) is of great concern in East Asian countries, and some estimates suggest that up to 70% of these cancers in women may be unrelated to tobacco smoking. 1,[5][6][7] Currently, LCINS is regarded as a distinct disease entity with a unique tumorigenic pattern, clinicopathologic features, and natural history.…”

Section: Introductionmentioning

confidence: 99%

“…EGFR mutations have been reported in approximately 50% of never-smoker lung cancer patients compared with 10% of smoker lung cancer patients. 2,[12][13][14] The high frequency of EGFR mutations in never-smoker patients is associated with dramatic and durable responses to EGFR tyrosine kinase inhibitors (TKIs). 2,[15][16][17][18][19][20] ALK rearrangement, which results from a small inversion within chromosome 2p, is a newly identified driver oncogene in nonsmall cell lung cancer (NSCLC).…”

Section: Introductionmentioning

confidence: 99%

“…2,[12][13][14] The high frequency of EGFR mutations in never-smoker patients is associated with dramatic and durable responses to EGFR tyrosine kinase inhibitors (TKIs). 2,[15][16][17][18][19][20] ALK rearrangement, which results from a small inversion within chromosome 2p, is a newly identified driver oncogene in nonsmall cell lung cancer (NSCLC). [21][22][23] Results from a recent clinical trial of crizotinib, an inhibitor of the met proto-oncogene (hepatocyte growth factor receptor [MET]) and ALK, demonstrated a remarkable response rate and benefit of progression-free survival in ALK-positive patients.…”

Section: Introductionmentioning

confidence: 99%

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Distinct clinical features and outcomes in never‐smokers with nonsmall cell lung cancer who harbor EGFR or KRAS mutations or ALK rearrangement

Kim

Shim

Chung

et al. 2011

Cancer

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135

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BACKGROUND:The objectives of this study were to determine the proportions of major oncogenic alterations and to examine survival in genotype-specific subsets of never-smokers with nonsmall cell lung cancer (NSCLC). METHODS:The authors concurrently analyzed mutations in the epidermal growth factor receptor (EGFR) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) genes and investigated anaplastic lymphoma kinase (ALK) gene rearrangements in samples from 229 never-smokers with NSCLC. ALK rearrangements were identified by fluorescent in situ hybridization and were confirmed by immunohistochemistry. Mutations in EGFR (exons 18 to 21) and KRAS (codons 12 and 13) were determined by direct sequencing. RESULTS: Of 229 tumors, the frequency of EGFR mutations, ALK rearrangements, KRAS mutations, and no mutations (wild type [WT]) in any of the 3 genes (WT/WT/WT) was 48%, 8.3%, 3.5%, and 40.2%, respectively. All genetic alterations were mutually exclusive. The median progression-free survival after treatment with EGFR tyrosine kinase inhibitors (TKIs) was 12.8 months, 6.3 months, 2.1 months, and 1.6 months in patients with EGFR mutations, the WT/WT/WT genotype, KRAS mutations, and ALK rearrangements, respectively. In a Cox regression model, the adjusted hazard ratio for the risk of disease progression after treatment with EGFR TKIs was 0.59 (95% confidence interval [CI], 0.40-0.87; P ¼ .008) for patients with EGFR mutations, 4.58 (95% CI, 2.07-10.15; P < .001) for patients with ALK rearrangements, and 4.23 (95% CI, 1.65-10.8; P ¼ .003) for patients with KRAS mutations. Overall survival also differed significantly among genotypes. CONCLUSIONS: To the authors' knowledge, this was the largest comprehensive and concurrent analysis to date of 3 major oncogenic alterations in a cohort of East Asian never-smokers with NSCLC. Because survival outcomes differed among genotypes, and drugs that target specific alterations currently are available, genetic profiling to identify genotype-specific subsets can lead to successful treatment with appropriate kinase inhibitors. Cancer 2012;118:729

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Association of epidermal growth factor receptor mutations with human papillomavirus 16/18 E6 oncoprotein expression in non–small cell lung cancer

Tung

Cheng³

et al. 2013

Cancer

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BACKGROUND: Lung cancers in women, in nonsmokers, and in patients with adenocarcinoma from Asia have more prevalent mutations in the epidermal growth factor receptor (EGFR) gene than their counterparts. However, the etiology of EGFR mutations in this population remains unclear. The authors hypothesized that the human papillomavirus (HPV) type 16=18 (HPV16=18) E6 oncoprotein may contribute to EGFR mutations in Taiwanese patients with lung cancer. METHODS: One hundred fifty-one tumors from patients with lung cancer were enrolled to determine HPV16=18 E6 and EGFR mutations using immunohistochemistry and direct sequencing, respectively. Levels of 8-oxo-7,8-dihydro-2 0 -deoxyguanosine (8-oxo-dG) in lung tumors and cells were evaluated using immunohistochemistry and liquid chromatography-mass spectrometry=mass spectrometry. An supF mutagenesis assay was used to determine H 2 O 2 -induced mutation rates of lung cancer cells with or without E6 expression. RESULTS: Patients with E6-positive tumors had a greater frequency of EGFR mutations than those with E6-negative tumors (41% vs 20%; P 5.006). Levels of 8-oxo-dG were correlated with EGFR mutations (36% vs 16%; P 5.012). Two stable clones of E6-overexpressing H157 and CL-3 cells were established for the supF mutagenesis assay. The data indicated that the cells with high E6 overexpression had higher H 2 O 2 -induced SupF gene mutation rates compared with the cells that expressed lower levels of E6 and compared with vector control cells. CONCLUSIONS: HPV16=18 E6 may contribute in part to EGFR mutations in lung cancer, at least in the Taiwanese population. Cancer 2013;119:3367-76. V C 2013 American Cancer Society.KEYWORDS: epidermal growth factor receptor; mutation; 8-oxo-7; 8-dihydro-2& prime;-deoxyguanosine; human papillomavirus; lung cancer. INTRODUCTIONLung cancer is the leading cause of cancer death and predominantly is induced by tobacco smoke. However, approximately 25% of all lung cancer worldwide is not attributed to smoking. 1,2 In addition, nonsmokers with lung cancer are identified more often Asian women than among Caucasian women. 3,4 Lung cancer in nonsmokers has recently been recognized as a disease entity distinct from tobacco smoke-associated lung cancer. 5,6 The activation of epidermal growth factor receptor (EGFR) by its gene mutations, including exon 19 in-frame deletions and exon 21 L858R substitution, are currently recognized as the most potent biologic predictors of EGFR tyrosine kinase inhibitor (TKI) sensitivity. 7 These mutations are observed in approximately 40% to 60% of lung cancers in neversmokers, compared with approximately 10% to 20% of tobacco smoke-related lung cancers. 8,9 Therefore, an exploration of the etiologic factor(s) in EGFR mutations may be useful in the prevention of lung cancer in nonsmokers, particularly among women.A high frequency of EGFR mutations are common in nonsmoking women with lung adenocarcinoma in Asian populations, including Taiwanese. 3,4 Nonsmokers with lung cancer more prevalently present with an adenocarci...

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Impact of Environmental Tobacco Smoke on the Incidence of Mutations in Epidermal Growth Factor Receptor Gene in Never-Smoker Patients With Non–Small-Cell Lung Cancer

Abstract: ETS exposure is negatively associated with EGFR mutations in never smokers with NSCLC.

Cited by 72 publications

References 33 publications

The Relationship Between Common EGFR, BRAF, KRAS Mutations and Prognosis in Advanced Stage Non-Small Cell Lung Cancer with Response to the Treatment in Turkey.

The Relationship Between Common EGFR, BRAF, KRAS Mutations and Prognosis in Advanced Stage Non-Small Cell Lung Cancer with Response to the Treatment in Turkey.

Distinct clinical features and outcomes in never‐smokers with nonsmall cell lung cancer who harbor EGFR or KRAS mutations or ALK rearrangement

Association of epidermal growth factor receptor mutations with human papillomavirus 16/18 E6 oncoprotein expression in non–small cell lung cancer

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