Polymorphisms in DNA repair genes and risk of non-Hodgkin's lymphoma in New South Wales, Australia

Min Shen, Mark P. Purdue, Anne Kricker, Qing Lan, Andrew E. Grulich, Claire M. Vajdic, Jennifer Turner, Denise Whitby, Stephen Chanock, Nathaniel Rothman, Bruce K. Armstrong

Research output: Contribution to journalArticle

Abstract

Background and Objectives: 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. Design: 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. Interpretation and 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.

Original languageEnglish (US)
Pages (from-to)1180-1185
Number of pages6
JournalHaematologica
Volume92
Issue number9
DOIs
StatePublished - Sep 2007
Externally publishedYes

Fingerprint

South Australia
New South Wales
DNA Repair
Non-Hodgkin's Lymphoma
Odds Ratio
Single Nucleotide Polymorphism
Confidence Intervals
Genes
DNA Damage
Lymphoma, Large B-Cell, Diffuse
Genomic Instability
Alkylating Agents
Linkage Disequilibrium
Environmental Exposure
Occupational Exposure
Case-Control Studies
Logistic Models
Population

Keywords

  • Case-control study
  • DNA repair
  • MGMT
  • Non-Hodgkin's lymphoma
  • Single nucleotide polymorphism

ASJC Scopus subject areas

  • Hematology

Cite this

Shen, M., Purdue, M. P., Kricker, A., Lan, Q., Grulich, A. E., Vajdic, C. M., ... Armstrong, B. K. (2007). Polymorphisms in DNA repair genes and risk of non-Hodgkin's lymphoma in New South Wales, Australia. Haematologica, 92(9), 1180-1185. https://doi.org/10.3324/haematol.11324

Polymorphisms in DNA repair genes and risk of non-Hodgkin's lymphoma in New South Wales, Australia. / Shen, Min; Purdue, Mark P.; Kricker, Anne; Lan, Qing; Grulich, Andrew E.; Vajdic, Claire M.; Turner, Jennifer; Whitby, Denise; Chanock, Stephen; Rothman, Nathaniel; Armstrong, Bruce K.

In: Haematologica, Vol. 92, No. 9, 09.2007, p. 1180-1185.

Research output: Contribution to journalArticle

Shen, M, Purdue, MP, Kricker, A, Lan, Q, Grulich, AE, Vajdic, CM, Turner, J, Whitby, D, Chanock, S, Rothman, N & Armstrong, BK 2007, 'Polymorphisms in DNA repair genes and risk of non-Hodgkin's lymphoma in New South Wales, Australia', Haematologica, vol. 92, no. 9, pp. 1180-1185. https://doi.org/10.3324/haematol.11324
Shen, Min ; Purdue, Mark P. ; Kricker, Anne ; Lan, Qing ; Grulich, Andrew E. ; Vajdic, Claire M. ; Turner, Jennifer ; Whitby, Denise ; Chanock, Stephen ; Rothman, Nathaniel ; Armstrong, Bruce K. / Polymorphisms in DNA repair genes and risk of non-Hodgkin's lymphoma in New South Wales, Australia. In: Haematologica. 2007 ; Vol. 92, No. 9. pp. 1180-1185.
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abstract = "Background and Objectives: 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. Design: 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. Interpretation and 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.",
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AU - Shen, Min

AU - Purdue, Mark P.

AU - Kricker, Anne

AU - Lan, Qing

AU - Grulich, Andrew E.

AU - Vajdic, Claire M.

AU - Turner, Jennifer

AU - Whitby, Denise

AU - Chanock, Stephen

AU - Rothman, Nathaniel

AU - Armstrong, Bruce K.

PY - 2007/9

Y1 - 2007/9

N2 - Background and Objectives: 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. Design: 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. Interpretation and 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.

AB - Background and Objectives: 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. Design: 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. Interpretation and 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.

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KW - Single nucleotide polymorphism

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