The last four decades have seen significant increase in the incidence of non-Hodgkin’s lymphoma (NHL) as a possible result of increasing environmental carcinogens exposure. Based on the increasing evidence for the association between carcinogens exposure related cancer risk and xenobiotic gene polymorphisms. We have undertaken a case control study on xenobiotic gene polymorphisms in Saudi individuals with a diagnosis of diffuse large B-cell lymphoma (DLBCL).

Polymorphisms in five genes (CYP1A1, GSTT1, GSTP1, GSTM1 and NQO1) were characterized in 187 individuals with DLBCL and 513 normal controls using polymerase chain reaction (PCR) based method. We chose the Saudi population as our study population because of its high consanguinity and its relative genetic homogeneity.

The CYP1A1*2C, GSTT1 null and GSTP1 TT genotype were all found to be significant predictors of DLBCL risk (odds ratio 6.62, 11.94 and 3.42 respectively). None of the other alleles tested for proved to be significant indicators of DLBCL risk. These results suggest that the risk of DLBCL may indeed be associated with xenobiotics - metabolism and thus with environmental exposures.

Table 1

Distribution of polymorphisms in healthy population and lymphoma patients.

PolymorphismGenotypeControl groupLymphoma patientspOR
CYP1A1 −/− 384(76.5%) 104(78.8%)   
*2A −/2A 105(20.9%) 24(18.18%) 0.543 0.844 
 2A/2A 13(2.6%) 3(2.27%) 1.000 0.852 
 2A allele 13% 11.36% 0.659 0.839 
CYP1A1 −/− 443(88.2%) 121(91.66%)   
*2B −/2B 50(10%) 10(7.58%) 0.505 0.732 
 2B/2B 9(1.8%) 1(0.76%) 0.697 0.407 
 2B allele 6.8% 4.55% 0.424 0.646 
CYP1A1 −/− 497(99%) 125(94.7%)   
*2C −/2C 5(1%) 4(3.03%) 0.090 3.181 
 2C/2C 0 3(2.27%) 0.008 ND 
 2C allele 0.5% 3.8% 0.011 6.627 
NQO1 C609T CC 295 (58.5%) 94 (62.7%)   
 CT 177 (35.1%) 37 (24.7%) 0.051 0.656 
 TT 32 (6.4%) 19 (8.7%) 0.059 1.863 
 CT+TT 209 (41.5%) 56 (37.3%) 0.395 0.841 
GSTP1 2293 CC 389 (76.3%) 113 (77.9%)   
 CT 113 (22.2%) 24 (16.6%) 0.240 0.731 
 TT 8 (1.5%) 8 (5.5%) 0.017 3.422 
 CT+TT 121 (23.7%) 32 (22%) 0.739 0.910 
GSTP1 A1578G AA 170 (33.5%) 56 (35%)   
 AG 271 (53.5%) 96 (60%) 0.772 1.075 
 GG 66 (13%) 8 (5%) 0.013 0.368 
 AG+GG 337 (66.5%) 104 (65%) 0.774 0.937 
GSTT1 P 385 (75%) 36 (20.1%)   
 D 128 (25%) 143 (79.9%) <0.001 11.948 
GSTM1 P 233 (45.4%) 91 (50%)   
 D 280 (54.6%) 91 (50%) 0.300 0.832 
PolymorphismGenotypeControl groupLymphoma patientspOR
CYP1A1 −/− 384(76.5%) 104(78.8%)   
*2A −/2A 105(20.9%) 24(18.18%) 0.543 0.844 
 2A/2A 13(2.6%) 3(2.27%) 1.000 0.852 
 2A allele 13% 11.36% 0.659 0.839 
CYP1A1 −/− 443(88.2%) 121(91.66%)   
*2B −/2B 50(10%) 10(7.58%) 0.505 0.732 
 2B/2B 9(1.8%) 1(0.76%) 0.697 0.407 
 2B allele 6.8% 4.55% 0.424 0.646 
CYP1A1 −/− 497(99%) 125(94.7%)   
*2C −/2C 5(1%) 4(3.03%) 0.090 3.181 
 2C/2C 0 3(2.27%) 0.008 ND 
 2C allele 0.5% 3.8% 0.011 6.627 
NQO1 C609T CC 295 (58.5%) 94 (62.7%)   
 CT 177 (35.1%) 37 (24.7%) 0.051 0.656 
 TT 32 (6.4%) 19 (8.7%) 0.059 1.863 
 CT+TT 209 (41.5%) 56 (37.3%) 0.395 0.841 
GSTP1 2293 CC 389 (76.3%) 113 (77.9%)   
 CT 113 (22.2%) 24 (16.6%) 0.240 0.731 
 TT 8 (1.5%) 8 (5.5%) 0.017 3.422 
 CT+TT 121 (23.7%) 32 (22%) 0.739 0.910 
GSTP1 A1578G AA 170 (33.5%) 56 (35%)   
 AG 271 (53.5%) 96 (60%) 0.772 1.075 
 GG 66 (13%) 8 (5%) 0.013 0.368 
 AG+GG 337 (66.5%) 104 (65%) 0.774 0.937 
GSTT1 P 385 (75%) 36 (20.1%)   
 D 128 (25%) 143 (79.9%) <0.001 11.948 
GSTM1 P 233 (45.4%) 91 (50%)   
 D 280 (54.6%) 91 (50%) 0.300 0.832 
View Large
Table 2

Distribution of combined GSTT1 and GSTM1 polymorphisms in case and control group.

GenotypeControlCasepOR
Null: Complete deletion of GSTT1 and GSTM1 allele 
Present 423 (82.8%) 109 (60.9%)   
Double Null 88 (17.2%) 70 (39.1%) <0.001 3.087 
GenotypeControlCasepOR
Null: Complete deletion of GSTT1 and GSTM1 allele 
Present 423 (82.8%) 109 (60.9%)   
Double Null 88 (17.2%) 70 (39.1%) <0.001 3.087 
View Large

Topics:
diffuse large b-cell lymphoma, enzymes, polymorphism, cytochrome p-450 cyp1a1, xenobiotics, chief complaint, lymphoma, polymerase chain reaction, carcinogens, consanguinity

Disclosure: No relevant conflicts of interest to declare.

Author notes

*

Corresponding author

2006, The American Society of Hematology
2006
Sign in via your Institution