Variation in DNA repair genes XRCC3, XRCC4, XRCC5 and susceptibility to myeloma

Patrick J. Hayden; Prerna Tewari; Derek W. Morris; Anthony Staines; Dominique Crowley; Alexandra Nieters; Nikolaus Becker; Silvia De sanjosé; Lenka Foretova; Marc Maynadié; Pier Luigi Cocco; Paolo Boffetta; Paul Brennan; Stephen J. Chanock; Paul V. Browne; Mark Lawler

doi:10.1093/hmg/ddm273

Variation in DNA repair genes XRCC3, XRCC4, XRCC5 and susceptibility to myeloma

Patrick J. Hayden, Prerna Tewari, Derek W. Morris, Anthony Staines, Dominique Crowley, Alexandra Nieters, Nikolaus Becker, Silvia De sanjosé, Lenka Foretova, Marc Maynadié, Pier Luigi Cocco, Paolo Boffetta, Paul Brennan, Stephen J. Chanock, Paul V. Browne, Mark Lawler

Research output: Contribution to journal › Article › peer-review

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Abstract

Cytogenetic analysis in myeloma reveals marked chromosomal instability. Both widespread genomic alterations and evidence of aberrant class switch recombination, the physiological process that regulates maturation of the antibody response, implicate the DNA repair pathway in disease pathogenesis. We therefore assessed 27 SNPs in three genes (XRCC3, XRCC4 and XRCC5) central to DNA repair in patients with myeloma and controls from the EpiLymph study and from an Irish hospital registry (n = 306 cases, 263 controls). For the haplotype-tagging SNP (htSNP) rs963248 in XRCC4, Allele A was significantly more frequent in cases than in controls (86.4 versus 80.8%; odds ratio 1.51; 95% confidence interval 1.10-2.08; P = 0.0133), as was the AA genotype (74 versus 65%) (P = 0.026). Haplotype analysis was performed using Unphased for rs963248 in combination with additional SNPs in XRCC4. The strongest evidence of association came from the A-T haplotype from rs963248-rs2891980 (P = 0.008). For XRCC5, the genotype GG from rs1051685 was detected in 10 cases from different national populations but in only one control (P = 0.015). This SNP is located in the 3′-UTR of XRCC5. Overall, these data provide support for the hypothesis that common variation in the genes encoding DNA repair proteins contributes to susceptibility to myeloma.

Original language	English (US)
Pages (from-to)	3117-3127
Number of pages	11
Journal	Human molecular genetics
Volume	16
Issue number	24
DOIs	https://doi.org/10.1093/hmg/ddm273
State	Published - Dec 15 2007
Externally published	Yes

ASJC Scopus subject areas

Molecular Biology
Genetics
Genetics(clinical)

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Hayden, P. J., Tewari, P., Morris, D. W., Staines, A., Crowley, D., Nieters, A., Becker, N., De sanjosé, S., Foretova, L., Maynadié, M., Cocco, P. L., Boffetta, P., Brennan, P., Chanock, S. J., Browne, P. V., & Lawler, M. (2007). Variation in DNA repair genes XRCC3, XRCC4, XRCC5 and susceptibility to myeloma. Human molecular genetics, 16(24), 3117-3127. https://doi.org/10.1093/hmg/ddm273

Hayden, PJ, Tewari, P, Morris, DW, Staines, A, Crowley, D, Nieters, A, Becker, N, De sanjosé, S, Foretova, L, Maynadié, M, Cocco, PL, Boffetta, P, Brennan, P, Chanock, SJ, Browne, PV & Lawler, M 2007, 'Variation in DNA repair genes XRCC3, XRCC4, XRCC5 and susceptibility to myeloma', Human molecular genetics, vol. 16, no. 24, pp. 3117-3127. https://doi.org/10.1093/hmg/ddm273

@article{af71e330c323492a82e6e64bbdc60725,

title = "Variation in DNA repair genes XRCC3, XRCC4, XRCC5 and susceptibility to myeloma",

abstract = "Cytogenetic analysis in myeloma reveals marked chromosomal instability. Both widespread genomic alterations and evidence of aberrant class switch recombination, the physiological process that regulates maturation of the antibody response, implicate the DNA repair pathway in disease pathogenesis. We therefore assessed 27 SNPs in three genes (XRCC3, XRCC4 and XRCC5) central to DNA repair in patients with myeloma and controls from the EpiLymph study and from an Irish hospital registry (n = 306 cases, 263 controls). For the haplotype-tagging SNP (htSNP) rs963248 in XRCC4, Allele A was significantly more frequent in cases than in controls (86.4 versus 80.8%; odds ratio 1.51; 95% confidence interval 1.10-2.08; P = 0.0133), as was the AA genotype (74 versus 65%) (P = 0.026). Haplotype analysis was performed using Unphased for rs963248 in combination with additional SNPs in XRCC4. The strongest evidence of association came from the A-T haplotype from rs963248-rs2891980 (P = 0.008). For XRCC5, the genotype GG from rs1051685 was detected in 10 cases from different national populations but in only one control (P = 0.015). This SNP is located in the 3′-UTR of XRCC5. Overall, these data provide support for the hypothesis that common variation in the genes encoding DNA repair proteins contributes to susceptibility to myeloma.",

author = "Hayden, {Patrick J.} and Prerna Tewari and Morris, {Derek W.} and Anthony Staines and Dominique Crowley and Alexandra Nieters and Nikolaus Becker and {De sanjos{\'e}}, Silvia and Lenka Foretova and Marc Maynadi{\'e} and Cocco, {Pier Luigi} and Paolo Boffetta and Paul Brennan and Chanock, {Stephen J.} and Browne, {Paul V.} and Mark Lawler",

note = "Funding Information: We wish to acknowledge the generous grant support of Cancer Research Ireland and the Health Research Board, Ireland. The Research Associate P.H. was supported by a grant from the Bone Marrow For Leukaemia Trust.",

year = "2007",

month = dec,

day = "15",

doi = "10.1093/hmg/ddm273",

language = "English (US)",

volume = "16",

pages = "3117--3127",

journal = "Human molecular genetics",

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T1 - Variation in DNA repair genes XRCC3, XRCC4, XRCC5 and susceptibility to myeloma

AU - Hayden, Patrick J.

AU - Tewari, Prerna

AU - Morris, Derek W.

AU - Staines, Anthony

AU - Crowley, Dominique

AU - Nieters, Alexandra

AU - Becker, Nikolaus

AU - De sanjosé, Silvia

AU - Foretova, Lenka

AU - Maynadié, Marc

AU - Cocco, Pier Luigi

AU - Boffetta, Paolo

AU - Brennan, Paul

AU - Chanock, Stephen J.

AU - Browne, Paul V.

AU - Lawler, Mark

N1 - Funding Information: We wish to acknowledge the generous grant support of Cancer Research Ireland and the Health Research Board, Ireland. The Research Associate P.H. was supported by a grant from the Bone Marrow For Leukaemia Trust.

PY - 2007/12/15

Y1 - 2007/12/15

N2 - Cytogenetic analysis in myeloma reveals marked chromosomal instability. Both widespread genomic alterations and evidence of aberrant class switch recombination, the physiological process that regulates maturation of the antibody response, implicate the DNA repair pathway in disease pathogenesis. We therefore assessed 27 SNPs in three genes (XRCC3, XRCC4 and XRCC5) central to DNA repair in patients with myeloma and controls from the EpiLymph study and from an Irish hospital registry (n = 306 cases, 263 controls). For the haplotype-tagging SNP (htSNP) rs963248 in XRCC4, Allele A was significantly more frequent in cases than in controls (86.4 versus 80.8%; odds ratio 1.51; 95% confidence interval 1.10-2.08; P = 0.0133), as was the AA genotype (74 versus 65%) (P = 0.026). Haplotype analysis was performed using Unphased for rs963248 in combination with additional SNPs in XRCC4. The strongest evidence of association came from the A-T haplotype from rs963248-rs2891980 (P = 0.008). For XRCC5, the genotype GG from rs1051685 was detected in 10 cases from different national populations but in only one control (P = 0.015). This SNP is located in the 3′-UTR of XRCC5. Overall, these data provide support for the hypothesis that common variation in the genes encoding DNA repair proteins contributes to susceptibility to myeloma.

AB - Cytogenetic analysis in myeloma reveals marked chromosomal instability. Both widespread genomic alterations and evidence of aberrant class switch recombination, the physiological process that regulates maturation of the antibody response, implicate the DNA repair pathway in disease pathogenesis. We therefore assessed 27 SNPs in three genes (XRCC3, XRCC4 and XRCC5) central to DNA repair in patients with myeloma and controls from the EpiLymph study and from an Irish hospital registry (n = 306 cases, 263 controls). For the haplotype-tagging SNP (htSNP) rs963248 in XRCC4, Allele A was significantly more frequent in cases than in controls (86.4 versus 80.8%; odds ratio 1.51; 95% confidence interval 1.10-2.08; P = 0.0133), as was the AA genotype (74 versus 65%) (P = 0.026). Haplotype analysis was performed using Unphased for rs963248 in combination with additional SNPs in XRCC4. The strongest evidence of association came from the A-T haplotype from rs963248-rs2891980 (P = 0.008). For XRCC5, the genotype GG from rs1051685 was detected in 10 cases from different national populations but in only one control (P = 0.015). This SNP is located in the 3′-UTR of XRCC5. Overall, these data provide support for the hypothesis that common variation in the genes encoding DNA repair proteins contributes to susceptibility to myeloma.

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DO - 10.1093/hmg/ddm273

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SP - 3117

EP - 3127

JO - Human molecular genetics

JF - Human molecular genetics

IS - 24

ER -

Variation in DNA repair genes XRCC3, XRCC4, XRCC5 and susceptibility to myeloma

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