BACKGROUND: Plasma organochlorines have been implicated to increase the risk of non-Hodgkin lymphoma (NHL), and interaction with the aryl hydrocarbon receptor gene (AHR) may modify this risk. METHODS: In this case-control study conducted in British Columbia, Canada, five single nucleotide polymorphisms (SNPs) of AHR were genotyped in 422 NHL cases and 459 controls to measure the association between individual SNPs, haplotypes, and risk of NHL. Pre-chemotherapy organochlorine levels were measured and gene-environment interaction analysis was performed. RESULTS: The IVS1 + 4640G/A SNP was significantly associated with NHL risk, with an odds ratio of 1.32 (95% CI = 1.05-1.65) for G/A or A/A genotypes compared to the G/G genotype. Interactions were observed with PCB 118, a known inducer of AHR, and chlordane-related analytes oxychlordane and trans-nonachlor, although no interactions were statistically significant after controlling for multiple comparisons. The observed interactions were consistent across NHL subtypes. CONCLUSION: Results suggest that the AHR gene may play a role in determining the risk of NHL with exposure to organochlorines, and highlight the importance of understanding gene-environment interactions.
BACKGROUND: Plasma organochlorines have been implicated to increase the risk of non-Hodgkin lymphoma (NHL), and interaction with the aryl hydrocarbon receptor gene (AHR) may modify this risk. METHODS: In this case-control study conducted in British Columbia, Canada, five single nucleotide polymorphisms (SNPs) of AHR were genotyped in 422 NHL cases and 459 controls to measure the association between individual SNPs, haplotypes, and risk of NHL. Pre-chemotherapy organochlorine levels were measured and gene-environment interaction analysis was performed. RESULTS: The IVS1 + 4640G/A SNP was significantly associated with NHL risk, with an odds ratio of 1.32 (95% CI = 1.05-1.65) for G/A or A/A genotypes compared to the G/G genotype. Interactions were observed with PCB 118, a known inducer of AHR, and chlordane-related analytes oxychlordane and trans-nonachlor, although no interactions were statistically significant after controlling for multiple comparisons. The observed interactions were consistent across NHL subtypes. CONCLUSION: Results suggest that the AHR gene may play a role in determining the risk of NHL with exposure to organochlorines, and highlight the importance of understanding gene-environment interactions.
Authors: Somiranjan Ghosh; Christopher A Loffredo; Partha S Mitra; Tomas Trnovec; Lubica Palkovicova Murinova; Eva Sovcikova; Eric P Hoffman; Kepher H Makambi; Sisir K Dutta Journal: Environ Sci Pollut Res Int Date: 2017-11-15 Impact factor: 4.223
Authors: Michael A Garland; Mitra C Geier; Sean M Bugel; Prarthana Shankar; Cheryl L Dunham; Joseph M Brown; Susan C Tilton; Robyn L Tanguay Journal: Toxicol Sci Date: 2020-07-01 Impact factor: 4.849
Authors: Sonia Sanna; Giannina Satta; Marina Padoan; Sara Piro; Angela Gambelunghe; Lucia Miligi; Giovanni Maria Ferri; Corrado Magnani; Giacomo Muzi; Luigi Rigacci; Maria Giuseppina Cabras; Emanuele Angelucci; Gian Carlo Latte; Attilio Gabbas; Maria Grazia Ennas; Pierluigi Cocco Journal: Int J Mol Epidemiol Genet Date: 2017-09-01
Authors: Barbara C Spink; Michael S Bloom; Susan Wu; Stewart Sell; Erasmus Schneider; Xinxin Ding; David C Spink Journal: Toxicol Appl Pharmacol Date: 2014-11-04 Impact factor: 4.219
Authors: June T Spector; Anneclaire J De Roos; Cornelia M Ulrich; Lianne Sheppard; Andreas Sjödin; Mark H Wener; Brent Wood; Anne McTiernan Journal: Environ Res Date: 2014-04-11 Impact factor: 6.498