Interaction between organochlorines and the AHR gene, and risk of non-Hodgkin lymphoma.
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.


CONCLUSIONS
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.
Ng
Carmen H
CH
BC Cancer Agency,Vancouver, BC, V5Z 1L3, Canada.
Janoo-Gilani
Rozmin
R
Sipahimalani
Payal
P
Gallagher
Richard P
RP
Gascoyne
Randy D
RD
Connors
Joseph M
JM
Weber
Jean-Philippe
JP
Lai
Agnes S
AS
Leach
Stephen
S
Le
Nhu D
ND
Brooks-Wilson
Angela R
AR
Spinelli
John J
JJ
D000328:Adult; D000368:Aged; D051792:Basic Helix-Loop-Helix Proteins; D001955:British Columbia; D016022:Case-Control Studies; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000097:blood*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D006843:Hydrocarbons, Chlorinated / Q000097:blood*; D008228:Lymphoma, Non-Hodgkin / Q000453:epidemiology / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics*; D012307:Risk Factors
D051792:Basic Helix-Loop-Helix Proteins; D004785:Environmental Pollutants; D006843:Hydrocarbons, Chlorinated; D018336:Receptors, Aryl Hydrocarbon; C111235:AHR protein, human