Association between xenobiotic gene polymorphisms and non-Hodgkin's lymphoma risk.
The last four decades have seen a significant increase in the incidence of non-Hodgkin's lymphoma (NHL) as a possible result of increasing environmental carcinogen exposure, particularly pesticides and solvents. Based on the increasing evidence for an association between carcinogen exposure-related cancer risk and xenobiotic gene polymorphisms, we have undertaken a case-control study of xenobiotic gene polymorphisms in individuals with a diagnosis of NHL. Polymorphisms of six xenobiotic genes (CYP1A1, GSTT1, GSTM1, PON1, NAT1, NAT2) were characterized in 169 individuals with NHL and 205 normal controls using polymerase chain reaction-based methods. Polymorphic frequencies were compared using Fisher's exact tests, and odds ratios for NHL risk were calculated. Among the NHL group, the incidence of GSTT1 null and PON1 BB genotypes were significantly increased compared with controls, 34% vs 14%, and 24% vs 11% respectively. Adjusted odds ratios calculated from multivariate analyses demonstrated that GSTT1 null conferred a fourfold increase in NHL risk (OR = 4.27; 95% CI, 2.40-7.61, P < 0.001) and PON1 BB a 2.9-fold increase (OR = 2.92; 95% CI, 1.49-5.72, P = 0.002). Furthermore, GSTT1 null combined with PON1 BB or GSTM1 null conferred an additional risk of NHL. This is the first time that a PON1 gene polymorphism has been shown to be associated with cancer risk. We conclude that the two polymorphisms, GSTT1 null and PON1 BB, are common genetic traits that pose low individual risk but may be important determinants of overall population NHL risk, particularly among groups exposed to NHL-related carcinogens.
Kerridge
Ian
I
Hunter Haematology Research Group, Newcastle Mater Hospital, Newcastle, Australia.
Lincz
Lisa
L
Scorgie
Fiona
F
Hickey
Danica
D
Granter
Neil
N
Spencer
Andrew
A
D001191:Arylamine N-Acetyltransferase / Q000235:genetics; D043303:Aryldialkylphosphatase; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D004950:Esterases / Q000235:genetics; D039603:Eukaryotic Initiation Factor-4G; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics*; D015999:Multivariate Analysis; D010448:Peptide Initiation Factors / Q000235:genetics; D011110:Polymorphism, Genetic; D012307:Risk Factors; D015262:Xenobiotics
D001191:Arylamine N-Acetyltransferase; D043303:Aryldialkylphosphatase; D019363:Cytochrome P-450 CYP1A1; D004950:Esterases; D039603:Eukaryotic Initiation Factor-4G; D005982:Glutathione Transferase; D010448:Peptide Initiation Factors; D015262:Xenobiotics; C491300:EIF4G2 protein, human; C478900:NAT2 protein, human; C413545:glutathione S-transferase T1; C468406:PON1 protein, human