Polymorphisms of CYP1A1 I462V and GSTM1 genotypes and lung cancer susceptibility in Mongolian

Aim: To study the genotype of cytochrome P450 1A1(CYP1A1) I462V and glutathions S-transferase M1( GSTM1) and the relationship of the genetic polymorphism of them with the susceptibility of lung cancer in Mongolia of China. 

Methods: Allele-specific PCR and a multiplex PCR were employed to identify the genotypes of I462V of CYP1A1 and GSTM1 in a case-control study of 210 lung cancer patients with bronchoscopy diagnosis and 210 matched controls free of malignancy.

Results: The frequencies of the variant CYP1A1(Val/Val) genotypes and GSTM1(-) in lung cancer groups were higher than that in control groups (15.24% vs 7.4% and 56.67% vs 40.95% ). The individuals who carried with CYP1A1(Val/Val) or GSTM1(-) genotype had a significantly higher risk of lung cancer, the OR is 2.56 and 1.89 respectively. Stratified histologically the relative risk increased to 2.6 - fold when the patients carried with two valine alleles than the ones carried one valine allele in cases of SCC. GSTM1(-) genotype is the risk factor of SCC (OR=2.39) and AC(OR=2.16). The presence of at least one Val allele of CYP1A1 and GSTM1(-), the risk of lung cancer was increased, the OR was 4.15 for one Val allele and GSTM1(-) and 2.67 for two Val alleles and GSTM1 Considering ages and smoking status, the risk of lung cancer increased when the age less than 50 who carried with CYP1A1 valine (one or two) alleles or the age during the 51 to 65 who carried with GSTM1(-) genotype. The light smokers with CYP1A1 valine alleles and GSTM1(-) have a high risk for lung cancer. No association was found between the light and heavy drinkers with the susceptibility of lung cancer and the genetic polymorphisms of CYP1A1 I462V and GSTM1(-). 

Conclusion: The valine allele of CYP1A1 was the risk factors of lung cancer especially for SCC and GSTM1(-) also was the risk factor of lung cancer and especially for SCC and AC of Mongolian, China. Light smoking has a influence each other with genotype of CYP1A1 I462V and GSTM1(-) and susceptibility of lung cancer. No relationship was found between the susceptibility of lung cancer and drinkers with genetic polymorphisms of CYP1A1 I462V and GSTM1(-). The influence of genotypes on the susceptibility of lung cancer may depend on the ages. There may be a synergetic interaction between CYP1A1 valine allele and GSTM1(-) genotypes on the elevated susceptibility of lung cancer. So do those genotypes with light smokers. Key words polymorphism; genotype; lung cancer; cytochrome P450；glutathione S-transferase Abbreviations: SCC, squamous cell carcinoma; AC, adenocarcinoma; SCLC, small cell lung cancer; LCLC, large cell lung cance

Current concepts on the role of inflammation in COPD and lung cancer

Chronic obstructive pulmonary disease (COPD) and lung cancer are leading cause of death, and both are associated with cigarette smoke exposure. It has been shown that 50–70% of patients diagnosed with lung cancer suffer from COPD, and reduced lung function is an important event in lung cancer suggesting an association between COPD and lung cancer. However, a causal relationship between COPD and lung tumorigenesis is not yet fully understood. Recent studies have suggested a central role of chronic inflammation in pathogenesis of both the diseases. For example, immune dysfunction, abnormal activation of NF-κB, epithelial-to-mesenchymal transition, altered adhesion signaling pathways, and extracellular matrix degradation/altered signaling are the key underlying mechanisms in both COPD and lung cancer. These parameters along with other processes, such as chromatin modifications/epigenetic changes, angiogenesis, and autophagy/apoptosis are altered by cigarette smoke, are crucial in the development of COPD and lung cancer. Understanding the cellular and molecular mechanisms underlying these processes will provide novel avenues for halting the chronic inflammation in COPD and devising therapeutic strategies against lung cancer

Immunotherapy of lung cancer: An update

In Germany lung cancer is the leading cause of cancer-associated death in men. Surgery, chemotherapy and radiation may enhance survival of patients suffering from lung cancer but the enhancement is typically transient and mostly absent with advanced disease; eventually more than 90% of lung cancer patients will die of disease. New approaches to the treatment of lung cancer are urgently needed. Immunotherapy may represent one new approach with low toxicity and high specificity but implementation has been a challenge because of the poor antigenic characterization of these tumors and their ability to escape immune responses. Several different immunotherapeutic treatment strategies have been developed. This review examines the current state of development and recent advances with respect to non-specific immune stimulation, cellular immunotherapy ( specific and non-specific), therapeutic cancer vaccines and gene therapy for lung cancer. The focus is primarily placed on immunotherapeutic cancer treatments that are already in clinical trial or well progressed in preclinical studies. Although there seems to be a promising future for immunotherapy in lung cancer, presently there is not standard immunotherapy available for clinical routine

RRx-001 in Refractory Small-Cell Lung Carcinoma: A Case Report of a Partial Response after a Third Reintroduction of Platinum Doublets.

RRx-001 is a pan-active, systemically nontoxic epigenetic inhibitor under investigation in advanced non-small cell lung cancer, small-cell lung cancer and high-grade neuroendocrine tumors in a Phase II clinical trial entitled TRIPLE THREAT (NCT02489903), which reexposes patients to previously effective but refractory platinum doublets after treatment with RRx-001. The purpose of this case study is first to report a partial response to carboplatin and etoposide in a patient with small-cell lung cancer pretreated with RRx-001, indicating episensitization or resensitization by epigenetic mechanisms, and second to discuss the literature related to small-cell lung cancer and episensitization

ANN for Lung Cancer Detection

In this paper, we developed an Artificial Neural Network (ANN) for detect the absence or presence of lung cancer in human body. Symptoms were used to diagnose the lung cancer, these symptoms such as Yellow fingers, Anxiety, Chronic Disease, Fatigue, Allergy, Wheezing, Coughing, Shortness of Breath, Swallowing Difficulty and Chest pain. They were used and other information about the person as input variables for our ANN. Our ANN established, trained, and validated using data set, which its title is “survey lung cancer”. Model evaluation showed that the ANN model is able to detect the absence or presence of lung cancer with 96.67 % accuracy

Lung Cancer Detection Using Artificial Neural Network

In this paper, we developed an Artificial Neural Network (ANN) for detect the absence or presence of lung cancer in human body. Symptoms were used to diagnose the lung cancer, these symptoms such as Yellow fingers, Anxiety, Chronic Disease, Fatigue, Allergy, Wheezing, Coughing, Shortness of Breath, Swallowing Difficulty and Chest pain. They were used and other information about the person as input variables for our ANN. Our ANN established, trained, and validated using data set, which its title is “survey lung cancer”. Model evaluation showed that the ANN model is able to detect the absence or presence of lung cancer with 96.67 % accuracy

Vermonters’ Opinions on Low-Dose CT Lung Cancer Screening

Introduction: Lung cancer is the number one cause of cancer death among men and women in Vermont and the United States. Smoking increases the risk of lung cancer—nearly 90% of lung cancer is due to smoking. Frequently, lung cancers do not present clinically until they are advanced stage and therefore prognosis is poor. However, if detected early lung cancers are more operable and patients have better outcomes. In December 2013 the US Preventive Services Task Force released new guidelines for lung cancer screening among current and former smokers ages 55 to 80. It is recommended that current and former (within 15 years of quitting) smokers of 30 pack years receive an annual low-dose CT scan. The objective of this project was to assess the level of knowledge and attitudes towards lung cancer screening with low-dose CT scanning among Vermonters in the Burlington area.https://scholarworks.uvm.edu/comphp_gallery/1205/thumbnail.jp

Transthyretin Stimulates Tumor Growth through Regulation of Tumor, Immune, and Endothelial Cells

Early detection of lung cancer offers an important opportunity to decrease mortality while it is still treatable and curable. Thirteen secretory proteins that are Stat3 downstream gene products were identified as a panel of biomarkers for lung cancer detection in human sera. This panel of biomarkers potentially differentiates different types of lung cancer for classification. Among them, the transthyretin (TTR) concentration was highly increased in human serum of lung cancer patients. TTR concentration was also induced in the serum, bronchoalveolar lavage fluid, alveolar type II epithelial cells, and alveolar myeloid cells of the CCSP-rtTA/(tetO)7-Stat3C lung tumor mouse model. Recombinant TTR stimulated lung tumor cell proliferation and growth, which were mediated by activation of mitogenic and oncogenic molecules. TTR possesses cytokine functions to stimulate myeloid cell differentiation, which are known to play roles in tumor environment. Further analyses showed that TTR treatment enhanced the reactive oxygen species production in myeloid cells and enabled them to become functional myeloid-derived suppressive cells. TTR demonstrated a great influence on a wide spectrum of endothelial cell functions to control tumor and immune cell migration and infiltration. TTR-treated endothelial cells suppressed T cell proliferation. Taken together, these 13 Stat3 downstream inducible secretory protein biomarkers potentially can be used for lung cancer diagnosis, classification, and as clinical targets for lung cancer personalized treatment if their expression levels are increased in a given lung cancer patient in the blood

Chronic obstructive pulmonary disease: a complex comorbidity of lung cancer

Chronic obstructive pulmonary disease (COPD) is a major burden throughout the world. It is associated with a significantly increased incidence of lung cancer and may influence treatment options and outcome. Impaired lung function confirming COPD is an independent risk factor for lung cancer. Oxidative stress and inflammation may be a key link between COPD and lung cancer, with numerous molecular markers being analysed to attempt to understand the pathway of lung cancer development. COPD negatively influences the ability to deliver radical treatment options, so attempts must be made to look for alternative methods of treating lung cancer, while aiming to manage the underlying COPD. Detailed assessment and management plans utilizing the multidisciplinary team must be made for all lung cancer patients with COPD to provide the best care possible.Journal of Comorbidity 2011;1(1):45–5