Gene variance in the nicotinic receptor cluster (CHRNA5-CHRNA3-CHRNB4) predicts death from cardiopulmonary disease and cancer in smokers.
J Intern Med
; 279(4): 388-98, 2016 Apr.
Article
in En
| MEDLINE
| ID: mdl-26689306
ABSTRACT
BACKGROUND:
Genetic variation in the cluster on chromosome 15, encoding the nicotinic acetylcholine receptor subunits (CHRNA5-CHRNA3-CHRNB4), has shown strong associations with tobacco consumption and an additional risk increase in smoking-related diseases such as chronic obstructive pulmonary disease (COPD), peripheral artery disease and lung cancer.OBJECTIVES:
To test whether rs1051730 (C/T), a tag for multiple variants in the CHRNA5-CHRNA3-CHRNB3 cluster, is associated with a change in risk of smoking-related mortality and morbidity in the Malmö Diet and Cancer study, a population-based prospective cohort study.METHODS:
At baseline participants were classified as current (n = 6951), previous (n = 8426) or never (n = 9417) smokers. Cox-proportional hazards models were used to determine the correlation between rs1051730 and incidence of first COPD, tobacco-related cancer, other cancer and cardiovascular disease (CVD), and total mortality due to these causes, during approximately 14 years of follow-up.RESULTS:
Amongst current smokers there were 480 first incident COPD events, 852 tobacco-related cancers, 810 other cancers and 1022 CVD events. A total of 1508 deaths occurred, including 500 due to CVD, 102 due to respiratory diseases and 677 due to cancer. In adjusted additive models, an increasing number of T alleles were associated with a gradual increase in total mortality, incident COPD and tobacco-related cancer, even after adjustment for smoking quantity. No significant associations were observed amongst never smokers.CONCLUSION:
Our data suggest that gene variance in the CHRNA5-CHRNA3-CHRNB4 cluster is associated with an increased risk of death, incidence of COPD and tobacco-related cancer in smokers. These findings indicate an individual susceptibility to tobacco use and its complications; this may be important when targeting and designing smoking cessation therapies.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Genetic Variation
/
Smoking
/
Receptors, Nicotinic
/
Pulmonary Disease, Chronic Obstructive
/
Peripheral Arterial Disease
/
Lung Neoplasms
/
Nerve Tissue Proteins
Type of study:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
J Intern Med
Journal subject:
MEDICINA INTERNA
Year:
2016
Document type:
Article
Affiliation country:
Sweden