TY - JOUR
T1 - Evaluation of genetic variation in the double-strand break repair pathway and bladder cancer risk
AU - Figueroa, Jonine D.
AU - Malats, Núria
AU - Rothman, Nathaniel
AU - Real, Francisco X.
AU - Silverman, Debra
AU - Kogevinas, Manolis
AU - Chanock, Stephen
AU - Yeager, Meredith
AU - Welch, Robert
AU - Dosemeci, Mustafa
AU - Tardón, Adonina
AU - Serra, Consol
AU - Carrato, Alfredo
AU - García-Closas, Reina
AU - Castaño-Vinyals, Gemma
AU - García-Closas, Montserrat
N1 - Funding Information:
We thank Robert C.Saal from Westat, Rockville, MD, and Leslie Carroll and Jane Wang from IMS, Silver Spring, MD, for their support in study and data management; Doug Richesson from DCEG, NCI, for his support in data analysis, Dr Maria Sala from IMIM, Barcelona, Spain, for her work in data collection; Francisco Fernandez for his work on data management, Dr Montserrat Torà for her work in the coordination of sample collection and blood processing; and physicians, nurses, interviewers and study participants for their efforts during field work. Lastly, Jonine Figueroa would like to thank the NCI Division of Cancer Prevention, Cancer Prevention Fellowship Program for their support.
PY - 2007/8
Y1 - 2007/8
N2 - The double-strand break DNA repair (DSBR) pathway is implicated in maintaining genomic stability and therefore could affect bladder cancer risk. Here we present data evaluating 39 single-nucleotide polymorphisms (SNPs) in seven candidate genes whose products are involved in DNA break sensing (NBS1, BRCA1 interacting genes BRIP1 and ZNF350), non-homologous end-joining (NHEJ) DNA repair (X RCC4) and homologous recombination (HR) repair (R AD51, XRCC2 and XRCC3). SNPs for RAD51 and XRCC2 covered most of the common variation. Associations with bladder cancer risk were evaluated in 1150 newly diagnosed cases of urinary bladder transitional cell carcinomas and 1149 controls conducted in Spain during 1997-2001. We found that the genetic variants evaluated significantly contributed to bladder cancer risk (global likelihood ratio test P = 0.01). Subjects with the ZNF350 R501S (rs2278415) variant allele showed significantly reduced risk compared with common homozygote variants, odds ratio (OR) [95% confidence interval (95% CI)]: 0.76 (0.62-0.93) per variant allele. Carriers of a putative functional SNP in intron 7 of XRCC4 (rs1805377) had significantly increased bladder cancer risk compared with common homozygotes: 1.33 (1.08-1.64) per variant allele. Lastly, XRCC2 homozygote variants for three promoter SNPs (rs10234749, rs6464268, rs3218373) and one non-synonymous SNP (rs3218536, R188H) were associated with reduced bladder cancer risk (ORs ranging from 0.36 to 0.50 compared with common homozygotes). Meta-analysis for XRCC3 T241M (rs861539) had a significant small increase in risk among homozygote variants: OR (95% CI) = 1.17 (1.00-1.36). Results from this study provide evidence for associations between variants in genes in the DSBR pathway and bladder cancers risk that warrant replication in other study populations.
AB - The double-strand break DNA repair (DSBR) pathway is implicated in maintaining genomic stability and therefore could affect bladder cancer risk. Here we present data evaluating 39 single-nucleotide polymorphisms (SNPs) in seven candidate genes whose products are involved in DNA break sensing (NBS1, BRCA1 interacting genes BRIP1 and ZNF350), non-homologous end-joining (NHEJ) DNA repair (X RCC4) and homologous recombination (HR) repair (R AD51, XRCC2 and XRCC3). SNPs for RAD51 and XRCC2 covered most of the common variation. Associations with bladder cancer risk were evaluated in 1150 newly diagnosed cases of urinary bladder transitional cell carcinomas and 1149 controls conducted in Spain during 1997-2001. We found that the genetic variants evaluated significantly contributed to bladder cancer risk (global likelihood ratio test P = 0.01). Subjects with the ZNF350 R501S (rs2278415) variant allele showed significantly reduced risk compared with common homozygote variants, odds ratio (OR) [95% confidence interval (95% CI)]: 0.76 (0.62-0.93) per variant allele. Carriers of a putative functional SNP in intron 7 of XRCC4 (rs1805377) had significantly increased bladder cancer risk compared with common homozygotes: 1.33 (1.08-1.64) per variant allele. Lastly, XRCC2 homozygote variants for three promoter SNPs (rs10234749, rs6464268, rs3218373) and one non-synonymous SNP (rs3218536, R188H) were associated with reduced bladder cancer risk (ORs ranging from 0.36 to 0.50 compared with common homozygotes). Meta-analysis for XRCC3 T241M (rs861539) had a significant small increase in risk among homozygote variants: OR (95% CI) = 1.17 (1.00-1.36). Results from this study provide evidence for associations between variants in genes in the DSBR pathway and bladder cancers risk that warrant replication in other study populations.
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U2 - 10.1093/carcin/bgm132
DO - 10.1093/carcin/bgm132
M3 - Article
C2 - 17557904
AN - SCOPUS:34548056355
SN - 0143-3334
VL - 28
SP - 1788
EP - 1793
JO - Carcinogenesis
JF - Carcinogenesis
IS - 8
ER -