| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Epidemiology and Prevention |
Department of Cancer Cell Biology, Harvard School of Public Health, Boston, Massachusetts 02115 [H. H. N., K. T. K.], and Section of Biostatistics and Epidemiology, Department of Community and Family Medicine, Dartmouth Medical School, Lebanon, New Hampshire 03756 [L. A. M., M. R. K.]
XRCC1, a protein directly involved in the repair of DNA base damage, contains at least three common polymorphisms. One of these, the codon 399 arg
gln variant, has been associated with several cancer-related biomarkers, suggesting it may have functional significance in exposure-induced cancers. However, results from case-control studies have yielded conflicting results. We investigated the XRCC1 arg399gln polymorphism and its interaction with carcinogen exposure in a large, population-based case-control study of non-melanoma skin cancer. Cases were derived from an incident survey of all newly diagnosed non-melanoma skin cancer in New Hampshire, and controls were population based and frequency matched to cases on age and sex (n = 1176). Exposure information was derived from a detailed interviewer-administered questionnaire, and XRCC1 genotype was determined from blood-derived DNA using a PCR-RFLP method. Overall, the XRCC1 homozygous variant gln399gln genotype was related to a significantly reduced risk of both basal cell [BCC; odds ratio (OR) 0.7, 95% confidence interval 0.4–1.0] and squamous cell carcinoma (SCC; OR 0.6, 95% confidence interval 0.3–0.9). There was no significant gene-environment interaction of the variant XRCC1 genotype and a history of therapeutic X-ray exposure. However, there was a statistically significant multiplicative interaction of XRCC1 genotype and lifetime number of sunburns in SCC [likelihood ratio test (2 d.f.), P < 0.02]. Although the absolute risk of SCC associated with sunburns was similar across genotypes, the relative risk of SCC associated with painful sunburn history was significantly higher for homozygous variants than wild types (OR 6.8 for gln399gln and 1.5 for arg399arg). In summary, our data show that the homozygous XRCC1 variant (gln399gln) is associated with a lower risk of non-melanoma skin cancer and suggest that the etiology of sunburn-related SCC may be significantly different by XRCC1 genotype. These data, using the classic skin carcinogenesis model, provide new insight on the role of the XRCC1 399 polymorphism in neoplasia and may help explain the conflicting results relating this polymorphism to cancer risk at various sites.
This article has been cited by other articles:
|
|
 |
|
  J. Lu, S. Zhang, D. Chen, H. Wang, W. Wu, X. Wang, Y. Lei, J. Wang, J. Qian, W. Fan, et al. Functional characterization of a promoter polymorphism in APE1/Ref-1 that contributes to reduced lung cancer susceptibility FASEB J, October 1, 2009; 23(10): 3459 - 3469. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Tanori, M. Mancuso, E. Pasquali, S. Leonardi, S. Rebessi, V. Di Majo, M.-N. Guilly, F. Giangaspero, V. Covelli, S. Pazzaglia, et al. PARP-1 cooperates with Ptc1 to suppress medulloblastoma and basal cell carcinoma Carcinogenesis, October 1, 2008; 29(10): 1911 - 1919. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. McCarty, T. J. Smith, W. Zhou, E. Gonzalez, Q. Quamruzzaman, M. Rahman, G. Mahiuddin, L. Ryan, L. Su, and D. C. Christiani Polymorphisms in XPD (Asp312Asn and Lys751Gln) genes, sunburn and arsenic-related skin lesions Carcinogenesis, August 1, 2007; 28(8): 1697 - 1702. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. V. Breton, W. Zhou, M. L. Kile, E.A. Houseman, Q. Quamruzzaman, M. Rahman, G. Mahiuddin, and D. C. Christiani Susceptibility to arsenic-induced skin lesions from polymorphisms in base excision repair genes Carcinogenesis, July 1, 2007; 28(7): 1520 - 1525. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. F. Giachino, P. Ghio, S. Regazzoni, G. Mandrile, S. Novello, G. Selvaggi, D. Gregori, M. DeMarchi, and G. V. Scagliotti Prospective Assessment of XPD Lys751Gln and XRCC1 Arg399Gln Single Nucleotide Polymorphisms in Lung Cancer Clin. Cancer Res., May 15, 2007; 13(10): 2876 - 2881. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Povey, F. Darakhshan, K. Robertson, Y. Bisset, M. Mekky, J. Rees, V. Doherty, G. Kavanagh, N. Anderson, H. Campbell, et al. DNA repair gene polymorphisms and genetic predisposition to cutaneous melanoma Carcinogenesis, May 1, 2007; 28(5): 1087 - 1093. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Zhu, M. Lai, H. Yang, J. Lin, M. Huang, H.B. Grossman, C. P. Dinney, and X. Wu Genotypes, haplotypes and diplotypes of XPC and risk of bladder cancer Carcinogenesis, March 1, 2007; 28(3): 698 - 703. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Hill, S. S. Wang, J. R. Cerhan, S. Davis, W. Cozen, R. K. Severson, P. Hartge, S. Wacholder, M. Yeager, S. J. Chanock, et al. Risk of non-Hodgkin lymphoma (NHL) in relation to germline variation in DNA repair and related genes Blood, November 1, 2006; 108(9): 3161 - 3167. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. A. Kocabas and B. Karahalil XRCC1 Arg399Gln Genetic Polymorphism in a Turkish Population International Journal of Toxicology, September 1, 2006; 25(5): 419 - 422. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Li, Z. Liu, L.-E Wang, S. S. Strom, J. E. Lee, J. E. Gershenwald, M. I. Ross, P. F. Mansfield, J. N. Cormier, V. G. Prieto, et al. Genetic variants of the ADPRT, XRCC1 and APE1 genes and risk of cutaneous melanoma Carcinogenesis, September 1, 2006; 27(9): 1894 - 1901. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. K. Thirumaran, J. L. Bermejo, P. Rudnai, E. Gurzau, K. Koppova, W. Goessler, M. Vahter, G. S. Leonardi, F. Clemens, T. Fletcher, et al. Single nucleotide polymorphisms in DNA repair genes and basal cell carcinoma of skin Carcinogenesis, August 1, 2006; 27(8): 1676 - 1681. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Miller, M. R. Karagas, P. Kraft, D. J. Hunter, P. J. Catalano, S. H. Byler, and H. H. Nelson XPA, haplotypes, and risk of basal and squamous cell carcinoma Carcinogenesis, August 1, 2006; 27(8): 1670 - 1675. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Ekstrom Smedby, C. M. Lindgren, H. Hjalgrim, K. Humphreys, C. Schollkopf, E. T. Chang, G. Roos, L. P. Ryder, K. I. Falk, J. Palmgren, et al. Variation in DNA Repair Genes ERCC2, XRCC1, and XRCC3 and Risk of Follicular Lymphoma. Cancer Epidemiol. Biomarkers Prev., February 1, 2006; 15(2): 258 - 265. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Hung, J. Hall, P. Brennan, and P. Boffetta Genetic Polymorphisms in the Base Excision Repair Pathway and Cancer Risk: A HuGE Review Am. J. Epidemiol., November 15, 2005; 162(10): 925 - 942. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W.-Y. Huang, W.-H. Chow, N. Rothman, J. Lissowska, V. Llaca, M. Yeager, W. Zatonski, and R. B. Hayes Selected DNA repair polymorphisms and gastric cancer in Poland Carcinogenesis, August 1, 2005; 26(8): 1354 - 1359. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Hu, H. Ma, F. Chen, Q. Wei, and H. Shen XRCC1 Polymorphisms and Cancer Risk: A Meta-analysis of 38 Case-Control Studies Cancer Epidemiol. Biomarkers Prev., July 1, 2005; 14(7): 1810 - 1818. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-T. Jeon, J. W. Kim, N.-H. Park, Y.-S. Song, S.-B. Kang, and H.-P. Lee DNA repair gene XRCC1 Arg399Gln polymorphism is associated with increased risk of uterine leiomyoma Hum. Reprod., June 1, 2005; 20(6): 1586 - 1589. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Shen, M. D. Gammon, M. B. Terry, L. Wang, Q. Wang, F. Zhang, S. L. Teitelbaum, S. M. Eng, S. K. Sagiv, M. M. Gaudet, et al. Polymorphisms in XRCC1 Modify the Association between Polycyclic Aromatic Hydrocarbon-DNA Adducts, Cigarette Smoking, Dietary Antioxidants, and Breast Cancer Risk Cancer Epidemiol. Biomarkers Prev., February 1, 2005; 14(2): 336 - 342. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. T. Kelsey, S. Park, H. H. Nelson, and M. R. Karagas A Population-Based Case-Control Study of the XRCC1 Arg399Gln Polymorphism and Susceptibility to Bladder Cancer Cancer Epidemiol. Biomarkers Prev., August 1, 2004; 13(8): 1337 - 1341. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Figueiredo, J. A. Knight, L. Briollais, I. L. Andrulis, and H. Ozcelik Polymorphisms XRCC1-R399Q and XRCC3-T241M and the Risk of Breast Cancer at the Ontario Site of the Breast Cancer Family Registry Cancer Epidemiol. Biomarkers Prev., April 1, 2004; 13(4): 583 - 591. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Zhu, M. R. Spitz, C. I. Amos, J. Lin, M. B. Schabath, and X. Wu An Evolutionary Perspective on Single-Nucleotide Polymorphism Screening in Molecular Cancer Epidemiology Cancer Res., March 15, 2004; 64(6): 2251 - 2257. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. A. Rybicki, D. V. Conti, A. Moreira, M. Cicek, G. Casey, and J. S. Witte DNA Repair Gene XRCC1 and XPD Polymorphisms and Risk of Prostate Cancer Cancer Epidemiol. Biomarkers Prev., January 1, 2004; 13(1): 23 - 29. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-O. Shu, Q. Cai, Y.-T. Gao, W. Wen, F. Jin, and W. Zheng A Population-Based Case-Control Study of the Arg399Gln Polymorphism in DNA Repair Gene XRCC1 and Risk of Breast Cancer Cancer Epidemiol. Biomarkers Prev., December 1, 2003; 12(12): 1462 - 1467. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Moullan, D. G. Cox, S. Angele, P. Romestaing, J.-P. Gerard, and J. Hall Polymorphisms in the DNA Repair Gene XRCC1, Breast Cancer Risk, and Response to Radiotherapy Cancer Epidemiol. Biomarkers Prev., November 1, 2003; 12(11): 1168 - 1174. [Abstract] [Full Text]
|
|
|
|
 |
|
 M.-W. Yu, S.-Y. Yang, I-J. Pan, C.-L. Lin, C.-J. Liu, Y.-F. Liaw, S.-M. Lin, P.-J. Chen, S.-D. Lee, and C.-J. Chen Polymorphisms in XRCC1 and Glutathione S-Transferase Genes and Hepatitis B-Related Hepatocellular Carcinoma J Natl Cancer Inst, October 1, 2003; 95(19): 1485 - 1488. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. L. Goode, C. M. Ulrich, and J. D. Potter Polymorphisms in DNA Repair Genes and Associations with Cancer Risk Cancer Epidemiol. Biomarkers Prev., December 1, 2002; 11(12): 1513 - 1530. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Seedhouse, R. Bainton, M. Lewis, A. Harding, N. Russell, and E. Das-Gupta The genotype distribution of the XRCC1 gene indicates a role for base excision repair in the development of therapy-related acute myeloblastic leukemia Blood, November 15, 2002; 100(10): 3761 - 3766. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. W. Mohrenweiser, T. Xi, J. Vazquez-Matias, and I. M. Jones Identification of 127Amino Acid Substitution Variants in Screening 37 DNA Repair Genes in Humans Cancer Epidemiol. Biomarkers Prev., October 1, 2002; 11(10): 1054 - 1064. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. J. Duell, E. A. Holly, P. M. Bracci, J. K. Wiencke, and K. T. Kelsey A Population-based Study of the Arg399Gln Polymorphism in X-Ray Repair Cross- Complementing Group 1 (XRCC1) and Risk of Pancreatic Adenocarcinoma Cancer Res., August 15, 2002; 62(16): 4630 - 4636. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
