Abstract
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.
Distribution of polymorphisms in healthy population and lymphoma patients.
| Polymorphism . | Genotype . | Control group . | Lymphoma patients . | p . | OR . |
|---|---|---|---|---|---|
| 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 |
| Polymorphism . | Genotype . | Control group . | Lymphoma patients . | p . | OR . |
|---|---|---|---|---|---|
| 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 |
Distribution of combined GSTT1 and GSTM1 polymorphisms in case and control group.
| Genotype . | Control . | Case . | p . | OR . |
|---|---|---|---|---|
| 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 |
| Genotype . | Control . | Case . | p . | OR . |
|---|---|---|---|---|
| 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 |
Disclosure: No relevant conflicts of interest to declare.
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