Lin Li

BACKGROUND: Mutations in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR) gene in lung cancers are associated with increased sensitivity of these cancers to drugs that inhibit EGFR kinase activity. However, the role of such mutations in the pathogenesis of lung cancers is unclear. METHODS: We sequenced exons 18-21 of the EGFR TK domain from genomic DNA isolated from 617 non-small-cell lung cancers (NSCLCs) and 524 normal lung tissue samples from the same patients and 36 neuroendocrine lung tumors collected from patients in Japan, Taiwan, the United States, and Australia and from 243 other epithelial cancers. Mutation status was compared with clinicopathologic features and with the presence of mutations in KRAS, a gene in the EGFR signaling pathway that is also frequently mutated in lung cancers. All statistical tests were two sided. RESULTS: We detected a total of 134 EGFR TK domain mutations in 130 (21%) of the 617 NSCLCs but not in any of the other carcinomas, nor in nonmalignant lung tissue from the same patients. In NSCLC patients, EGFR TK domain mutations were statistically significantly more frequent in never smokers than ever smokers (51% versus 10%), in adenocarcinomas versus cancer of other histologies (40% versus 3%), in patients of East Asian ethnicity versus other ethnicities (30% versus 8%), and in females versus males (42% versus 14%; all P < .001). EGFR TK domain mutation status was not associated with patient age at diagnosis, clinical stage, the presence of bronchioloalveolar histologic features, or overall survival. The EGFR TK domain mutations we detected were of three common types: in-frame deletions in exon 19, single missense mutations in exon 21, and in-frame duplications/insertions in exon 20. Rare missense mutations were also detected in exons 18, 20, and 21. KRAS gene mutations were present in 50 (8%) of the 617 NSCLCs but not in any tumors with an EGFR TK domain mutation. CONCLUSIONS: Mutations in either the EGFR TK domain or the KRAS gene can lead to lung cancer pathogenesis. EGFR TK domain mutations are the first molecular change known to occur specifically in never smokers.

BACKGROUND: Lung cancer has been the leading cause of cancer-related deaths worldwide for many years. This study aimed to investigate the global patterns and trends of lung cancer. METHODS: Lung cancer incidence and mortality were derived from the GLOBOCAN 2020 database. Continuous data from Cancer Incidence in Five Continents Time Trends were used to analyze the temporal trends from 2000 to 2012 using Joinpoint regression, and average annual percent changes were calculated. The association between the Human Development Index and lung cancer incidence and mortality was assessed by linear regression. RESULTS: An estimated 2.2 million new lung cancer cases and 1.8 million lung cancer-related deaths occurred in 2020. The age-standardized incidence rate (ASIR) ranged from 36.8 per 100,000 in Demark to 5.9 per 100,000 in Mexico. The age-standardized mortality rate (ASMR) varied from 32.8 per 100,000 in Poland to 4.9 per 100,000 in Mexico. Both ASIR and ASMR were approximately twice higher in men than in women. The ASIR of lung cancer showed a downward trend in the United States of America (USA) between 2000 and 2012, and was more prominent in men. The age-specific incidence rates of lung cancer for ages of 50 to 59 years showed an upward trend in China for both men and women. CONCLUSIONS: The burden of lung cancer is still unsatisfactory, especially in developing countries like China. Considering the effectiveness of tobacco control and screening in developed countries, such as the USA, there is a need to strengthen health education, accelerate the establishment of tobacco control policies and regulations, and improve early cancer screening awareness to reduce the future burden of lung cancer.

OBJECTIVES: To estimate the effectiveness of endoscopic screening programme in reducing incidence and mortality of upper gastrointestinal cancer in high risks areas of China. DESIGN: This multicentre population-based cohort study was conducted in six areas in China from 2005 to 2015. All permanent residents aged 40 to 69 years were identified as target subjects. We refer to those who were invited for screening collectively as the invited group. Of these, we classify those who were invited and undertook endoscopic screening as the screened group and those who were invited but did not accept screening as the non-screened group. Target subjects who were not invited to the screening were assigned to the control group. The effectiveness of the endoscopic screening and screening programme were evaluated by comparing reductions in incidence and mortality from upper gastrointestinal cancer in the screened and invited group with control group. RESULTS: Our cohort analysis included 637 500 people: 299 483 in the control group and 338 017 in the invited to screening group, 113 340 (33.53%) of whom were screened eventually. Compared with subjects in the control group, upper gastrointestinal cancer incidence and mortality decreased by 23% (relative risk (RR)=0.77, 95% CI 0.74 to 0.81) and 57% (RR=0.43, 95% CI 0.40 to 0.47) in the screened group, respectively, and by 14% (RR=0.86, 95% CI 0.84 to 0.89) and 31% (RR=0.69, 95% CI 0.66 to 0.72) in the invited group, respectively. CONCLUSION: Among individuals aged 40 to 69 years in high risk areas of upper gastrointestinal cancer, one-time endoscopic screening programme was associated with a significant decrease in upper gastrointestinal cancer incidence and mortality.

The receptor for advanced glycation end products (RAGE) is a pattern recognition receptor (PRR) that interacts with diverse endogenous ligands. Ligation of RAGE triggers a series of cellular signaling events, including the activation of transcription factor NF-kappaB, leading to the production of pro-inflammatory cytokines, and causing inflammation. While acute inflammation serves to resolve pathogen infection and stresses, which promote tissue repair, persistent inflammation results in maladaptive tissue remodeling and damage. RAGE signaling has been implicated in multiple detrimental human illnesses including diabetes, atherosclerosis, arthritis, and Alzheimer's disease. In addition, prolonged inflammation often serves as the precursor for arterial remodeling that underlies the exponential increase of age-associated arterial diseases. Despite the significant progress and exciting discoveries in RAGE research, little is known on the biochemistry of RAGE and the signaling mechanism of RAGE remains poorly defined. The biological impact of RAGE signaling in clinical situations and aging-associated diseases also remains to be fully realized. This review attempts to provide a comprehensive summary on both recent findings and missing pieces of the RAGE puzzle.