Plasma organochlorines, interaction between the aryl hydrocarbon receptor gene and organochlorines, and risk of non-Hodgkin lymphoma

The association between plasma organochlorine exposure and increased risk for non-Hodgkin lymphoma (NHL) has been documented, although results are not consistent. No studies have yet explored gene-environment interactions with organochlorine exposure, which may provide more insight into etiology of disease. One candidate gene to study such gene-environment interactions is the aryl hydrocarbon receptor (AHR) gene, which is involved in detoxification of organochlorines in the body. This case-control study was conducted to measure the association between plasma organochlorines and NHL risk, and how variants in the AHR gene may modify this risk. All HIV-negative NHL cases aged 20-79 were diagnosed between March 2000 and February 2004, and resided in the Greater Vancouver or Greater Victoria regions. Controls frequency matched by age, sex and region were identified from the Client Registry of the BC Ministry of Health. Demographic information was collected by telephone interview. 791 cases and 797 controls provided a DNA sample for genotyping of AHR, and seven single nucleotide polymorphisms (SNPs) were genotyped. Pre-chemotherapy blood samples from 422 cases and 460 controls were utilized for organochlorine measurement. Levels of 14 polychlorinated biphenyl (PCB) congeners and 11 organochlorine pesticide analytes were determined. Logistic regression was used to evaluate the association between AHR SNPs and risk of NHL, lipid-adjusted organochlorine levels and risk of NHL, and interaction between AHR SNPs and organochlorines. We found significant associations with several PCB congeners and other organochlorines. Organochlorines significantly associated with NHL include PCB congeners 99, 118, 138, 153, 156, 170, 180, and 187 as well as pesticides β-HCCH, DDE, hexachlorobenzene, mirex, oxychlordane and trans-nonachlor. The odds ratios for the highest versus lowest exposure categories for these organochlorines ranged from 1.4 to 2.7. The AHR IVS1+4640G/A SNP (rs17722841) was found to increase the risk of NHL. The odds ratio for the G/A or A/A allele compared to the G/G allele was 1.3 (95% CI=1.1-1.6). Significant interactions were also found between this allele and the organochlorines PCB 118, oxychlordane, and trans-nonachlor. For oxychlordane the odds ratio for the highest versus lowest exposure categories was 3.2 (95% CI=1.8-5.5) in the G/G genotype, but was not significant in the G/A or A/A genotypes (OR 1.3, 95%CI=0.5-3.4). The strong association observed for various PCB congeners and other organochlorines confirms the increased risk of NHL from organochlorine exposure. Results suggest the role of organochlorines in NHL etiology may involve the AHR pathway.Medicine, Faculty ofPopulation and Public Health (SPPH), School ofGraduat