The influence of gene-gene and gene-environment interactions on the risk of asbestosis

Our plain-English summary of The influence of gene-gene and gene-environment interactions on the risk of asbestosis, by A. Franko, V. Dolžan, N. Arnerić, et al (BioMed Research International, 2013).

The study

• Authors: A. Franko, V. Dolžan, N. Arnerić, M. Dodič-Fikfak
• Journal: BioMed Research International
• Published: 2013;2013:405743
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

This study investigated the influence of gene-gene and gene-environment interactions on the risk of developing asbestosis. The study comprised 262 cases with asbestosis and 265 controls with no asbestos-related disease previously studied for MnSOD, ECSOD, CAT, GSTT1, GSTM1, GSTP1, and iNOS polymorphisms. Data on cumulative asbestos and smoking were available for all subjects. To assess gene-gene and gene-environmental interactions, logistic regression was used. The associations between MnSOD Ala -9Val polymorphism and the risk of asbestosis and between iNOS genotypes and asbestosis were modified by CAT -262 C > T polymorphism (P = 0.038; P = 0.031). A strong interaction was found between GSTM1-null polymorphism and smoking (P = 0.007), iNOS (CCTTT) n polymorphism and smoking (P = 0.054), and between iNOS (CCTTT) n polymorphism and cumulative asbestos exposure (P = 0.037). The findings of this study suggest that the interactions between different genotypes, genotypes and smoking, and between genotypes and asbestos exposure have an important influence on the development of asbestosis and should be seriously considered in future research on occupational/environmental asbestos-related diseases.

In plain English

This Slovenian nested case-control study tested whether gene variants, smoking and asbestos exposure interacted on asbestosis risk. It included 262 people with asbestosis and 265 with no asbestos-related disease. All had been occupationally exposed to asbestos at the Salonit Anhovo cement manufacturing plant. They came from 2,080 exposed workers seen by a state board from 1998 to 2003. Single-gene results appeared in the group's earlier papers. Smoking was not associated with asbestosis (OR 0.98, 95% CI 0.69 to 1.39), while log-transformed cumulative asbestos exposure was (OR 3.21, 95% CI 2.43 to 4.23). The CAT variant modified how both the MnSOD and iNOS variants related to asbestosis (P = 0.038; P = 0.031). The GSTM1-null genotype interacted with smoking (P = 0.007); the iNOS variant interacted with smoking (P = 0.054) and cumulative exposure (P = 0.037). The authors concluded that their findings suggest these interactions have an important influence on the development of asbestosis and deserve serious consideration in future research. They called for larger studies of whether other gene variants modify or confound the link between cumulative exposure and asbestosis.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Nested case-control study using logistic regression to test gene-gene and gene-environment interactions
• Who was studied: 262 cases with asbestosis and 265 controls with no asbestos-related disease. All were drawn from a cohort of 2,080 asbestos-exposed workers presented at the State Board for the Recognition of Occupational Asbestos Diseases, Ljubljana, Slovenia, between January 1, 1998 and December 31, 2003.
• Exposure: Occupational asbestos exposure at the Salonit Anhovo cement manufacturing plant, Slovenia. Exposure was expressed as cumulative asbestos exposure in fibres/cm3-years, estimated from a job exposure matrix. Smoking history and gene variants (MnSOD, ECSOD, CAT, GSTT1, GSTM1, GSTP1, iNOS) were also studied. Fiber types are not specified in this article.
• Main results:
  • Across all subjects, smoking (ever versus never) was not associated with asbestosis: OR 0.98, 95% CI 0.69 to 1.39.
  • Across all subjects, log-transformed cumulative asbestos exposure was associated with asbestosis: OR 3.21, 95% CI 2.43 to 4.23.
  • The CAT −262 C>T variant modified the MnSOD–asbestosis association (interaction OR 4.49, 95% CI 1.08 to 18.61, P = 0.038). Among carriers of the CAT −262 TT genotype only, MnSOD −9Ala/Val plus Val/Val versus Ala/Ala had OR 2.67 (95% CI 0.57 to 13.07; P printed as 0.004).
  • The CAT −262 C>T variant modified the iNOS–asbestosis association (interaction OR 4.78, 95% CI 1.15 to 19.81, P = 0.031). Among CAT −262 TT carriers only, iNOS LL versus SL plus SS had OR 5.14 (95% CI 1.30 to 20.36).
  • GSTM1-null status modified the smoking–asbestosis association (interaction OR 2.67, 95% CI 1.31 to 5.46, P = 0.007). Among people with the GSTM1-null genotype, ever versus never smoking had OR 1.48 (95% CI 0.92 to 2.39).
  • The iNOS variant modified the smoking–asbestosis association (interaction OR 2.00, 95% CI 0.99 to 4.03, P = 0.054). Among people with the iNOS LL genotype, ever versus never smoking had OR 1.39 (95% CI 0.84 to 2.30).
  • Only the iNOS variant modified the association between cumulative asbestos exposure and asbestosis (interaction with log cumulative exposure OR 0.55, 95% CI 0.31 to 0.97, P = 0.037). Comparing exposure above 11.23 with exposure at or below 11.23 fibres/cm3-years gave OR 3.09 (95% CI 1.81 to 5.25) for iNOS LL and OR 5.74 (95% CI 3.30 to 9.99) for iNOS SL plus SS.
  • No interaction was found between the other genotypes studied.
• The authors' conclusion: The authors concluded that their findings suggest interactions between genotypes, between genotypes and smoking, and between genotypes and asbestos exposure have an important influence on the development of asbestosis. They said these interactions should be seriously considered in future research.
• Limitations the authors state:
  • The authors stated that additional studies with more subjects are needed to clarify whether other genetic variants modify or confound the association between cumulative asbestos exposure and asbestosis.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Asbestosis.

Medical terms in this study, explained in our Lexicon: Asbestos Exposure.

Related studies

• Genome-wide Gene-Asbestos Exposure Interaction Association Study Identifies a Common Susceptibility Variant on 22q13.31 Associated with Lung Cancer Risk — C.Y. Liu, I. Stücker, et al. (2015)
• Assessment of "gene-environment" interaction in cases of familial and sporadic pancreatic cancer — T.P. Yeo, R.H. Hruban, et al. (2009)
• Polymorphisms in oxidative stress-related genes are not associated with prostate cancer risk in heavy smokers — J.Y. Choi, M.L. Neuhouser, et al. (2007)
• Gene-asbestos interaction in malignant pleural mesothelioma susceptibility — S. Tunesi, D. Ferrante, et al. (2015)
• The influence of genetic polymorphisms of GSTP1 on the development of asbestosis — A. Franko, V. Dolzan, et al. (2008)
• Inducible nitric oxide synthase genetic polymorphism and risk of asbestosis — A. Franko, M. Dodič-Fikfak, et al. (2011)

Browse more research in BioMed Research International, or return to medical research.