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- Manuguerra, M., et al.
(författare)
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Multi-factor dimensionality reduction applied to a large prospective investigation on gene-gene and gene-environment interactions
- 2007
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Ingår i: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 28:2, s. 414-422
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Tidskriftsartikel (refereegranskat)abstract
- It is becoming increasingly evident that single-locus effects cannot explain complex multifactorial human diseases like cancer. We applied the multi-factor dimensionality reduction (MDR) method to a large cohort study on gene-environment and gene-gene interactions. The study (case-control nested in the EPIC cohort) was established to investigate molecular changes and genetic susceptibility in relation to air pollution and environmental tobacco smoke (ETS) in non-smokers. We have analyzed 757 controls and 409 cases with bladder cancer (n = 124), lung cancer (n = 116) and myeloid leukemia (n = 169). Thirty-six gene variants (DNA repair and metabolic genes) and three environmental exposure variables (measures of air pollution and ETS at home and at work) were analyzed. Interactions were assessed by prediction error percentage and cross-validation consistency (CVC) frequency. For lung cancer, the best model was given by a significant gene-environment association between the base excision repair (BER) XRCC1-Arg399Gln polymorphism, the double-strand break repair (DSBR) BRCA2-Asn372His polymorphism and the exposure variable 'distance from heavy traffic road', an indirect and robust indicator of air pollution (mean prediction error of 26%, P < 0.001, mean CVC of 6.60, P = 0.02). For bladder cancer, we found a significant 4-loci association between the BER APE1-Asp148Glu polymorphism, the DSBR RAD52-3'-untranslated region (3'-UTR) polymorphism and the metabolic gene polymorphisms COMT-Val158Met and MTHFR-677C > T (mean prediction error of 22%, P < 0.001, mean CVC consistency of 7.40, P < 0.037). For leukemia, a 3-loci model including RAD52-2259C > T, MnSOD-Ala9Val and CYP1A1-Ile462Val had a minimum prediction error of 31% (P < 0.001) and a maximum CVC of 4.40 (P = 0.086). The MDR method seems promising, because it provides a limited number of statistically stable interactions; however, the biological interpretation remains to be understood.
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- Modig, Lars, 1976-, et al.
(författare)
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Vehicle exhaust outside the home and onset of asthma among adults
- 2009
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 33:6, s. 1261-1267
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Tidskriftsartikel (refereegranskat)abstract
- Few studies have investigated the relationship between vehicle exhaust and the new onset of asthma among adults. The aim of the present prospective cohort study was to investigate the relationship between the cumulative incidence of asthma and onset of asthma among adults and vehicle exhaust concentrations at home. Participants from three Swedish cities included in the Respiratory Health in Northern Europe cohort constituted the study population. Exposure at each participant's home was calculated using dispersion models. We also used <50 m distance to nearest major road as a more simple indicator of exposure. The adjusted model included 3,609 participants, of which 107 were classified as onset cases and 55 as true incident cases of asthma. There was a positive association between asthma onset (odds ratio (OR) per 10 microg x m(-3) 1.46, 95% confidence interval (CI) 1.07-1.99) and incident asthma (OR per 10 microg x m(-3) 1.54, 95% CI 1.00-2.36) and the levels of nitrogen dioxide (NO(2)), which remained statistically significant after adjusting for potential confounders. The relationship between asthma and NO(2) was not significantly modified by sex, hay fever or wheeze. The risk of developing asthma was also significantly related to living close to a major road. The current study suggests that elevated levels of vehicle exhaust outside the home increase the risk of onset and incident asthma among adults.
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