The TERT-CLPTM1L lung cancer susceptibility variant associates with higher DNA adduct formation in the lung.

Genome-wide association studies have provided evidence that common variation at 5p15.33 [telomerase reverse transcriptase (TERT)-cleft lip and palate transmembrane 1-like (CLPTM1L)], 6p21.33 and 15q25.

A comprehensive analysis of phase I and phase II metabolism gene polymorphisms and risk of non-small cell lung cancer in smokers.

Lung cancer is a leading cause of cancer mortality worldwide with smoking and occupational exposure to carcinogenic compounds as the major risk factors. Susceptibility to lung cancer is affected by existence of polymorphic genes controlling the levels of metabolic activation and detoxification of carcinogens. We have investigated 105 single nucleotide polymorphisms (SNPs) in 31 genes from the phase I and phase II metabolism genes and antioxidant defense genes for association with the risk of non-small cell lung cancer (NSCLC) in a Norwegian population-based study.

Frequency of TP53 mutations in relation to Arg72Pro genotypes in non small cell lung cancer.

Mutations in the TP53 gene are important events during human lung carcinogenesis. The TP53 gene harbors several polymorphisms, and functional studies have shown that the Arg72Pro polymorphism alters both wild-type and mutant p53 protein activity. Thus, we hypothesized that certain Arg72Pro genotypes may influence the frequency and pattern of somatic mutations in TP53.

Polymorphisms of dopamine receptor/transporter genes and risk of non-small cell lung cancer.

Background: The dopaminergic pathway may be of interest in assessing risk of non-small cell lung cancer (NSCLC). Dopamine receptors are expressed in alveolar epithelial cells and human lung tumours, and dopamine inhibits both cell proliferation in vitro and growth of lung tumour xenografts in nude mice. Moreover, dopamine selectively inhibits the vascular permeability and angiogenic activity of vascular endothelial growth factor (VPF/VEGF).

Msh2 deficiency increases susceptibility to benzo[a]pyrene-induced lymphomagenesis.

DNA mismatch repair (MMR) is essential for repair of single-base mismatches and insertion/deletion loops. MMR proteins also participate in cellular response to DNA damaging agents such as various alkylating agents. Mice deficient in the MMR gene Msh2 develop tumors earlier after exposure to alkylating agents when compared to unexposed mice.

Polymorphisms of DNA repair genes and risk of non-small cell lung cancer.

Lung cancer is a leading cause of cancer mortality with an inter-individual difference in susceptibility to the disease. The inheritance of low-efficiency genotypes involved in DNA repair and replication may contribute to the difference in susceptibility. We investigated 44 single nucleotide polymorphisms (SNPs) in 20 DNA repair genes including nucleotide excision repair (NER) genes XPA, ERCC1, ERCC2/XPD, ERCC4/XPF and ERCC5/XPG; base excision repair (BER) genes APE1/APEX, OGG1, MPG, XRCC1, PCNA, POLB, POLiota, LIG3 and EXO1; double-strand break repair (DSB-R) genes XRCC2, XRCC3, XRCC9, NBS1 and ATR; and direct damage reversal (DR) gene MGMT/AGT.

Chromosome aberrations in tunnel workers exposed to acrylamide and N-methylolacrylamide.

Objectives: The aim of this study was to examine chromosome aberrations in 25 tunnel workers exposed to acrylamide-containing grout in injection work.

Methods: Blood samples were collected from 25 exposed and 25 unexposed tunnel workers matched for age, gender, and smoking habits. Whole blood was cultured for 50-53 hours according to conventional methods.

Interleukin 1 receptor antagonist gene polymorphism and risk of lung cancer: a possible interaction with polymorphisms in the interleukin 1 beta gene.

Tobacco smoking is the main risk factor for lung cancer. Only 10-15% of smokers develop lung cancer, suggesting that genetic factors are of importance in determining individual susceptibility to the disease. Several studies in recent years indicate that chronic inflammation is a cofactor in lung carcinogenesis.

Metabolic gene polymorphisms and lung cancer risk in non-smokers. An update of the GSEC study.

Background: Since genetic factors may play an important role in lung cancer development at low dose carcinogen exposure, non-smokers are a good model to study genetic susceptibility and its interaction with environmental factors.

Materials And Methods: We evaluated the role of the metabolic gene polymorphisms CYP1A1MspI, CYP1A1Ile462Val, GSTM1, and GSTT1 in non-smoker lung cancer patients from the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens (GSEC). Non-smokers (defined as subjects who never smoked on a regular basis) were selected from the GSEC database.

Polymorphisms in genes involved in xenobiotic metabolism and lung cancer risk under the age of 60 years. A pooled study of lung cancer patients in Denmark and Norway.

The genetic susceptibility hypothesis has been used to explain why only a minority of smokers develop lung cancer. Only few studies have studied the role of polymorphisms in phase-I and II metabolizing genes, among young lung cancer patients. We have pooled the individual data of three studies from Denmark and Norway, including 320 patients diagnosed with non-small cell lung cancer at age 59 or below, and 618 age and gender matched controls.

CYP1A1, GSTM1 and GSTT1 polymorphisms and lung cancer: a pooled analysis of gene-gene interactions.

Gene-environment interactions have been extensively studied in lung cancer. It is likely that several genetic polymorphisms cooperate in increasing the individual risk. Therefore, the study of gene-gene interactions might be important to identify high-susceptibility subgroups.

Polymorphisms of the interleukin-1 beta gene are associated with increased risk of non-small cell lung cancer.

Lung cancer is one of the leading causes of cancer death worldwide. Tobacco smoking is the main risk factor for lung cancer. Less than 20% of smokers develop lung cancer in their lifetime, however, indicating individual variations in lung cancer risk.

Pooled analysis of the CYP1A1 exon 7 polymorphism and lung cancer (United States).

Objective: Cytochrome P450 1A1 plays a major role in the bioactivation of a number of tobacco procarcinogens. Much interest has focused on a polymorphism in exon 7 of the CYP1A1 gene which has been associated with a more inducible form of the enzyme. However, past results of its association with lung cancer have been inconsistent, especially in Caucasians.

Meta- and pooled analyses of the effects of glutathione S-transferase M1 polymorphisms and smoking on lung cancer risk.

Susceptibility to lung cancer may in part be attributable to inter-individual variability in metabolic activation or detoxification of tobacco carcinogens. The glutathione S-transferase M1 (GSTM1) genetic polymorphism has been extensively studied in this context; two recent meta-analyses of case-control studies suggested an association between GSTM1 deletion and lung cancer. At least 15 studies have been published after these overviews.