Polymorphisms in DNA repair genes and risk of non-Hodgkin's lymphoma in New South Wales, Australia.
OBJECTIVE
A number of occupational and environmental exposures that can directly or indirectly cause DNA damage have been proposed as risk factors for non-Hodgkin's lymphoma (NHL). The human DNA damage repair system can recognize and repair such damage and maintain genomic stability. We investigated whether putatively functional single-nucleotide polymorphisms (SNP) in DNA repair genes influence susceptibility to NHL in a population-based case-control study conducted in Australia.


METHODS
A total of 561 cases and 506 controls were included in the analysis. Twenty-two SNP in 14 DNA repair genes were genotyped by a TaqMan-based assay. Unconditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI), adjusting for age, sex, residence, and ethnicity.


RESULTS
Two SNP in MGMT (Ile143Val and Lys178Arg) were in complete linkage disequilibrium and associated with increased risk of NHL (Ile143Val, Ile/Val vs. Ile/Ile, OR: 1.26; 95% CI: 0.93-1.70; Val/Val vs. Ile/Ile, OR: 2.55; 95% CI: 0.98-6.63; p trend: 0.024). These SNP were associated with increased risk of several NHL subtypes. In addition, the XRCC1 Arg194Trp polymorphism was associated with decreased NHL risk (Arg/Trp vs. Arg/Arg, OR: 0.72; 95% CI: 0.49-1.07; Trp/Trp vs. Arg/Arg, OR: 0.45; 95% CI: 0.10-1.99; p trend: 0.059), mainly in diffuse large B-cell lymphoma.


CONCLUSIONS
The association of genetic variants in MGMT with increased risk of NHL suggests that alkyl adducts may contribute to lymphomagenesis, and points to environmental and endogenous alkylating agents as possible risk factors for NHL. However, given that these results were based on a small number of variant carriers and the possibility that these results may have arisen due to chance, replication in other studies is needed.
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20892-7240, USA. shenmi@mail.nih.gov
Min
M
Shen
Mark P
MP
Purdue
Anne
A
Kricker
Qing
Q
Lan
Andrew E
AE
Grulich
Claire M
CM
Vajdic
Jennifer
J
Turner
Denise
D
Whitby
Stephen
S
Chanock
Nathaniel
N
Rothman
Bruce K
BK
Armstrong
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D015254:DNA Modification Methylases / Q000235:genetics; D004260:DNA Repair / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009517:New South Wales; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics; D000076105:X-ray Repair Cross Complementing Protein 1
D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes