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CHRNA5/CHRNA3 Locus Associates with Increased Mortality among Smokers.

https://arctichealth.org/en/permalink/ahliterature287426
Source
COPD. 2016 Aug;13(4):464-70
Publication Type
Article
Date
Aug-2016
Author
Henna Kupiainen
Mikko Kuokkanen
Jukka Kontto
Jarmo Virtamo
Veikko Salomaa
Ari Lindqvist
Maritta Kilpeläinen
Tarja Laitinen
Source
COPD. 2016 Aug;13(4):464-70
Date
Aug-2016
Language
English
Publication Type
Article
Keywords
Aged
Female
Finland
Genetic Predisposition to Disease
Humans
Logistic Models
Lung Neoplasms - genetics - mortality
Male
Middle Aged
Mortality
Neoplasms - genetics - mortality
Nerve Tissue Proteins - genetics
Polymorphism, Genetic
Polymorphism, Single Nucleotide
Prognosis
Proportional Hazards Models
Pulmonary Disease, Chronic Obstructive - genetics - mortality
Receptors, Nicotinic - genetics
Smoking - genetics - mortality
Abstract
Polymorphisms in the nicotinic acetylcholine receptor gene (CHRNA5/CHRNA3 locus) have been associated with several smoking related traits such as nicotine dependence, cigarette consumption, smoking cessation, lung cancer, and COPD. The aim of this candidate gene study was to study the locus among the Finnish COPD patients and long-term smokers with regard to COPD risk, smoking behavior, cancer, and all-cause mortality. Genotyping of rs1051730, the locus tagging SNP was done in two longitudinal cohorts: Finnish COPD patients (N = 575, 74% men) and long-term smokers, all men (N = 1911). Finnish population sample (N = 1730) was used as controls. The analyses were done using logistic and Cox regression. The main findings were that the minor allele increased the risk of COPD when compared to the Finnish population at large (OR = 1.4, 95% CI 1.2-1.7, p = 3.2 × 10-5). Homozygosity for the risk allele was associated in both cohorts with all-cause mortality (crude HR 2.2, 95% CI 1.2-3.8 and 1.3, 95% CI 1.1-1.5, respectively), with any type of cancer (crude OR 2.3, 95% CI 1.0-5.1) among the COPD patients and with the number of pack-years (crude OR 1.4, 95% CI 1.1-1.9) among the male smokers. CHRNA5/CHRNA3 locus tagged by rs1051730, which has been previously associated with several smoking related diseases was now shown to be associated also with increased all-cause mortality among long-term smokers with or without clinical COPD further emphasizing the clinical importance of the finding.
PubMed ID
26751916 View in PubMed
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Comparison of in vivo somatic cell mutation, chromosome aberration, sister chromatid exchange, micronuclei formation and urine mutagenicity in steel foundry workers.

https://arctichealth.org/en/permalink/ahliterature103352
Source
Prog Clin Biol Res. 1990;340C:377-86
Publication Type
Article
Date
1990

Genome-wide analysis of survival in early-stage non-small-cell lung cancer.

https://arctichealth.org/en/permalink/ahliterature89154
Source
J Clin Oncol. 2009 Jun 1;27(16):2660-7
Publication Type
Article
Date
Jun-1-2009
Author
Huang Yen-Tsung
Heist Rebecca S
Chirieac Lucian R
Lin Xihong
Skaug Vidar
Zienolddiny Shanbeh
Haugen Aage
Wu Michael C
Wang Zhaoxi
Su Li
Asomaning Kofi
Christiani David C
Author Affiliation
Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
Source
J Clin Oncol. 2009 Jun 1;27(16):2660-7
Date
Jun-1-2009
Language
English
Publication Type
Article
Keywords
Aged
Cadherins - genetics
Carcinoma, Non-Small-Cell Lung - genetics - mortality - pathology
Chromosomes, Human, Pair 3
Chromosomes, Human, Pair 5
Chromosomes, Human, Pair 8
Cohort Studies
Female
Gene Expression Profiling - methods
Gene Expression Regulation, Neoplastic
Gene Frequency
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Intracellular Signaling Peptides and Proteins - genetics
Kaplan-Meiers Estimate
Lung Neoplasms - genetics - mortality - pathology
Male
Massachusetts - epidemiology
Middle Aged
Neoplasm Staging
Norway - epidemiology
Nuclear Proteins - genetics
Oligonucleotide Array Sequence Analysis
Polymorphism, Single Nucleotide
Predictive value of tests
Prognosis
Proportional Hazards Models
Protein Tyrosine Phosphatases - genetics
Protein-Serine-Threonine Kinases - genetics
RNA-Binding Proteins - genetics
Reproducibility of Results
Risk assessment
Risk factors
Time Factors
Tumor Markers, Biological - genetics
Abstract
PURPOSE: Lung cancer, of which 85% is non-small-cell (NSCLC), is the leading cause of cancer-related death in the United States. We used genome-wide analysis of tumor tissue to investigate whether single nucleotide polymorphisms (SNPs) in tumors are prognostic factors in early-stage NSCLC. PATIENTS AND METHODS: One hundred early-stage NSCLC patients from Massachusetts General Hospital (MGH) were used as a discovery set and 89 NSCLC patients collected by the National Institute of Occupational Health, Norway, were used as a validation set. DNA was extracted from flash-frozen lung tissue with at least 70% tumor cellularity. Genome-wide genotyping was done using the high-density SNP chip. Copy numbers were inferred using median smoothing after intensity normalization. Cox models were used to screen and validate significant SNPs associated with the overall survival. RESULTS: Copy number gains in chromosomes 3q, 5p, and 8q were observed in both MGH and Norwegian cohorts. The top 50 SNPs associated with overall survival in the MGH cohort (P
PubMed ID
19414679 View in PubMed
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Tumor expression of S100A6 correlates with survival of patients with stage I non-small-cell lung cancer.

https://arctichealth.org/en/permalink/ahliterature92790
Source
Lung Cancer. 2009 Mar;63(3):410-7
Publication Type
Article
Date
Mar-2009
Author
De Petris Luigi
Orre Lukas M
Kanter Lena
Pernemalm Maria
Koyi Hirsh
Lewensohn Rolf
Lehtiö Janne
Author Affiliation
Karolinska Biomics Center, Karolinska Intitutet, Stockholm, Sweden.
Source
Lung Cancer. 2009 Mar;63(3):410-7
Date
Mar-2009
Language
English
Publication Type
Article
Keywords
Adult
Aged
Aged, 80 and over
Carcinoma, Non-Small-Cell Lung - genetics - mortality - pathology
Cell Cycle Proteins - biosynthesis - genetics
DNA, Neoplasm - genetics
Epidermal Growth Factor
Female
Follow-Up Studies
Gene Expression Regulation, Neoplastic
Humans
Immunohistochemistry
Lung Neoplasms - genetics - mortality - pathology
Male
Middle Aged
Neoplasm Staging
Oligonucleotide Array Sequence Analysis
Prognosis
S100 Proteins - biosynthesis - genetics
Survival Rate
Sweden - epidemiology
Abstract
BACKGROUND: In a previously published in vitro study based on top-down proteomics we found that the calcium-binding proteins S100A6 and S100A4 were affected by exposure to ionizing radiation in a p53-dependent fashion. Both proteins showed post-translational modification changes, and S100A6 also showed increased expression and translocation in response to irradiation. Aim of the present study was to evaluate the expression of S100A6 and S100A4 in non-small-cell lung cancer (NSCLC). METHODS: S100A6 expression on archival tumor cell lysates from 39 patients with radically resected NSCLC was assessed with SELDI-TOF-MS. S100A6 identity was confirmed using a SELDI-based antibody-capture method on lysates from the A549 lung cancer cell line, cell lysates from two freshly prepared NSCLC samples, four plasma samples and one pleural effusion sample. Immunostainings for S100A6, S100A4 and p53 were performed on tissue microarrays containing 103 stage I surgically resected NSCLC cases and 14 normal lung parenchyma specimens. RESULTS: The presence of post-translationally modified S100A6 forms was confirmed with SELDI-MS on enriched tumor cell lysates, as well as in plasma and pleural effusion samples. In addition, high S100A6 peak intensity was associated with longer median survival (35 months vs. 18 months for high and low peak intensity, respectively; p=n.s.). The immunohistochemical analysis showed that 25% of tumors were S100A6 positive. S100A6 expression correlated directly with non-squamous histology (p
PubMed ID
18620780 View in PubMed
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