Cigarette smoking is strongly associated with mutation of the K-ras gene in patients with primary adenocarcinoma of the lung

Ahrendt, Steven A.; Decker, P; Alawi, Enas; Zhu, Yong-Ran; Sánchez-Céspedes, Montserrat; Yang, Stephen C.; Haasler, George B.; Kajdacsy-Balla, André; Demeure, Michael J.; Sidransky, David

doi:10.1002/1097-0142(20010915)92:6<1525::aid-cncr1478>3.0.co;2-h

Cited by 400 publications

(279 citation statements)

References 17 publications

(16 reference statements)

Supporting

Mentioning

249

Contrasting

Unclassified

Order By: Relevance

“…As KRAS mutation is found mainly in smokers [6,33], the negative prognostic value of KRAS mutation may be related to the poor performance status associated with smoking [34]. In our study, no significant difference was observed in survival when stratified according to smoking status in the entire patient population.…”

Section: Discussioncontrasting

confidence: 49%

“…In the western world, in patients with lung adenocarcinoma, KRAS mutations are the most common (18-38% of cases), followed by mutations in the epidermal growth factor receptor (EGFR) gene (5-15% of cases) [5][6][7][8]. In Hungary, the incidence of KRAS mutation in lung adenocarcinoma is 29.5% (based on the analysis of 6250 patients; unpublished data).…”

Section: Introductionmentioning

confidence: 99%

“…In Hungary, the incidence of KRAS mutation in lung adenocarcinoma is 29.5% (based on the analysis of 6250 patients; unpublished data). Smoking status influences the mutation of these two genes: KRAS mutation is found mainly in smokers, whereas the mutation of EGFR gene is more frequent in non-smokers [6,9].…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, the presence of KRAS mutations seems to be mutually exclusive with EGFR mutations, and is associated with the absence of response to EGFR-TKIs [16][17][18]. It has been confirmed that smokers with adenocarcinoma of the lung are more likely to have KRAS mutation positive tumors compared to non-smokers [6]. Erlotinib treatment is particularly effective in terms of survival and tumor response in patients with the aforementioned clinicopathological characteristics.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Effectiveness of erlotinib treatment in advanced KRAS mutation-negative lung adenocarcinoma patients: Results of a multicenter observational cohort study (MOTIVATE)

et al. 2014

View full text Add to dashboard Cite

a b s t r a c tObjectives: Erlotinib is an epidermal growth factor receptor tyrosine-kinase inhibitor (EGFR-TKI), used for the treatment of non-small cell lung cancer. As the clinical significance of KRAS mutational status has not yet been clearly determined in this setting, our aim was to investigate the efficacy of erlotinib in advanced KRAS mutation-negative lung adenocarcinoma patients. Materials and methods:MOTIVATE is an open-label, multicenter, observational trial with Tarceva ® (erlotinib) monotherapy. Enrolled patients with advanced (stage IIIB/IV) KRAS wild type (WT) lung adenocarcinoma refractory to one or two courses of prior chemotherapy were treated with erlotinib at 150 mg/day. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS) and best tumor response rate (RR). Results and conclusion: In total, 327 patients were included. Median PFS and OS were 3.3 and 14.4 months, respectively. Three patients (1.2%) had complete response, 51 patients (20.2%) had partial response and 123 patients (48.8%) had SD.Significantly longer median PFS and OS were observed in Eastern Oncology Cooperative Group Performance Status (ECOG PS) 0-1 patients, as compared to ECOG PS 2-3 patients. The longest median OS (20.5 months) was found in patients with ECOG PS 0-1 who received erlotinib as a second-line therapy. There was no difference in median OS in cohorts stratified to disease stage and smoking status. Female patients had both longer median PFS and OS. Disease control rate was 70.2%.Our results suggest that erlotinib represents a valid treatment option for patients with KRAS WT lung adenocarcinoma and, moreover, that KRAS mutation analysis could help to identify clinically relevant subgroups of NSCLC patients that may benefit from EGFR-TKI therapy.

show abstract

Section: Discussioncontrasting

confidence: 49%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Effectiveness of erlotinib treatment in advanced KRAS mutation-negative lung adenocarcinoma patients: Results of a multicenter observational cohort study (MOTIVATE)

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Most lung cancer results from multiple changes in the genome of susceptible pulmonary cells caused by exposure to carcinogens found in tobacco smoke, the environment, and the workplace. Patients exposed to a smoking environment had more frequent gene mutations, such as the epidermal growth factor receptor ( EGFR ) gene, 3 the K-ras gene, 4 and the p53 gene. 5,6 …”

Section: Introductionmentioning

confidence: 99%

Smoker and non-smoker lung adenocarcinoma is characterized by distinct tumor immune microenvironments

et al. 2018

OncoImmunology

View full text Add to dashboard Cite

Tobacco smoking causes DNA damages in epithelial cells and immune dysfunction in the lung, which collectively contribute to lung carcinogenesis and progression. However, potential mechanisms by which tumor-infiltrating immune cells contribute to lung cancer survival and their differential contributions in ever-smokers and never-smokers are not well studied. Here, we performed integrative analysis of 11 lung cancer gene-expression datasets, including 1,111 lung adenocarcinomas and 200 adjacent normal lung samples. Distinct pathways were altered in lung carcinogenesis in ever-smokers and never-smokers. Never-smoker patients had a better outcome than ever-smoker patients. We characterized compositional patterns of 21 types of immune cells in lung adenocarcinomas and revealed the complex association between immune cell composition and clinical outcomes. Interestingly, we found two subsets of immune cells, mast cells and CD4+ memory T cells, which had completely opposite associations with outcomes in resting and activated status. We further discovered that several chemokines and their associated receptors (e.g., CXCL11-CX3CR1 axis) were selectively altered in lung tumors in response to cigarette smoking and their abundances showed stronger correlation with fractions of these immune subsets in ever-smokers than never-smokers. The status switched from the resting to activated forms in mast cells and CD4+ memory T cells might manifest some important processes induced by cigarette smoking during tumor development and progression. Our findings suggested that aberrant activation of mast cells and CD4+ memory T cells plays crucial roles in cigarette smoking-induced immune dysfunction in the lung, which contributes to tumor development and progression.

show abstract

Tobacco Use and Cancer

Hecht

2007

The Cancer Handbook

View full text Add to dashboard Cite

Although considerable advances have been achieved in tobacco control, the use of tobacco products continues to be an immense problem worldwide. There are about 1200 million smokers in the world and hundreds of millions of smokeless tobacco users. The link between tobacco use and cancer is unguestionable, with cigarette smoking causing about 30% of all cancer mortality in developed countries. Experimental studies have firmly established the cancer causing properties of tobacco products in laboratory animals. Carcinogens in tobacco products have been identified and their mechanisms of action are well understood. Biomarkers related to these carcinogens have been developed and widely applied. Collectively, the currently available data provide a strong framework for further mechanistic understanding leading to continued progress in tobacco control and prevention of tobacco‐induced cancer.

show abstract

Cigarette smoking is strongly associated with mutation of the K-ras gene in patients with primary adenocarcinoma of the lung

Cited by 400 publications

References 17 publications

Effectiveness of erlotinib treatment in advanced KRAS mutation-negative lung adenocarcinoma patients: Results of a multicenter observational cohort study (MOTIVATE)

Effectiveness of erlotinib treatment in advanced KRAS mutation-negative lung adenocarcinoma patients: Results of a multicenter observational cohort study (MOTIVATE)

Smoker and non-smoker lung adenocarcinoma is characterized by distinct tumor immune microenvironments

Tobacco Use and Cancer

Contact Info

Product

Resources

About