| 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 [E. J. D., K. T. K.], and Department of Epidemiology and Biostatistics, University of California at San Francisco, San Francisco, California 94143 [E. A. H., P. M. B., J. K. W.]
XRCC1 (X-ray repair cross-complementing group 1) is a base excision repair protein that plays a central role in the repair of DNA strand breaks and base damage from a variety of endogenous and exogenous oxidants including tobacco smoke. One genetic polymorphism (G
A, ArgGln at codon 399) occurs within a poly(ADP-ribose) polymerase binding region and within the central breast cancer susceptibility gene 1 product COOH terminus domain of XRCC1. The variant 399Gln allele of XRCC1 has been associated with elevated biomarkers of DNA damage in human cells. We conducted an analysis of the Arg399Gln polymorphism in XRCC1 using genomic DNA, and questionnaire information from 309 cases of pancreatic adenocarcinoma and 964 controls that were part of a population-based, case-control study conducted in the San Francisco Bay Area between 1994 and 2001. We genotyped individuals using a mass spectrometry-based method. Because smoking and obesity are known and suspected pancreas cancer risk factors, and have been associated with DNA damage and oxidative stress in target tissues, we estimated odds ratios (ORs), interaction contrast ratios (ICRs), and 95% confidence intervals for the combined effects of XRCC1 genotype and smoking or body mass index (in kg/m2). We also assessed potential gene-gene interactions between polymorphisms in XRCC1 and CYP1A1, GSTT1, and GSTM1. We found little or no evidence for an association between XRCC1 genotype and pancreatic cancer among Caucasians, African-Americans, or Asians. There was evidence for interaction between XRCC1 399Gln and smoking that was stronger among women than men. Relative to never active or passive smokers with the Arg/Arg genotype, the age- and race-adjusted ORs and ICRs (95% confidence limits) for heavy smoking (
41 pack-years) were: for Gln/Gln or Arg/Gln genotypes [women OR = 7.0 (2.4, 21), ICR = 3.1 (0.03, 6.2); men OR = 2.4 (1.1, 5.0), ICR = 1.3 (-0.20, 2.8)]; and for the Arg/Arg genotype [women OR = 2.2 (0.73, 6.4); men OR = 1.5 (0.68, 3.2)]. Analyses of combined genotypes suggested an interaction between XRCC1 (Gln/Gln or Arg/Gln) and GSTT1/GSTM1-null/null among women but not among men. There was no evidence of interaction between XRCC1 genotype and body mass index. Our results suggest that the XRCC1 399Gln allele is a potentially important determinant of susceptibility to smoking-induced pancreatic cancer. Our findings, including stronger associations and interactions among women, require replication in additional study populations.
This article has been cited by other articles:
|
|
 |
|
  D. Li, H. Suzuki, B. Liu, J. Morris, J. Liu, T. Okazaki, Y. Li, P. Chang, and J. L. Abbruzzese DNA Repair Gene Polymorphisms and Risk of Pancreatic Cancer Clin. Cancer Res., January 15, 2009; 15(2): 740 - 746. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Suzuki, Y. Li, X. Dong, M. M. Hassan, J. L. Abbruzzese, and D. Li Effect of Insulin-Like Growth Factor Gene Polymorphisms Alone or In Interaction with Diabetes on the Risk of Pancreatic Cancer Cancer Epidemiol. Biomarkers Prev., December 1, 2008; 17(12): 3467 - 3473. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. R. McWilliams, W. R. Bamlet, J. M. Cunningham, E. L. Goode, M. de Andrade, L. A. Boardman, and G. M. Petersen Polymorphisms in DNA Repair Genes, Smoking, and Pancreatic Adenocarcinoma Risk Cancer Res., June 15, 2008; 68(12): 4928 - 4935. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. J. Duell, P. M. Bracci, J. H. Moore, R. D. Burk, K. T. Kelsey, and E. A. Holly Detecting Pathway-Based Gene-Gene and Gene-Environment Interactions in Pancreatic Cancer Cancer Epidemiol. Biomarkers Prev., June 1, 2008; 17(6): 1470 - 1479. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Gao, D. K. Price, T. Sissung, E. Reed, and W. D. Figg Ethnic disparities in Americans of European descent versus Americans of African descent related to polymorphic ERCC1, ERCC2, XRCC1, and PARP1 Mol. Cancer Ther., May 1, 2008; 7(5): 1246 - 1250. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Chan, F. Wang, and E. A. Holly Whole Grains and Risk of Pancreatic Cancer in a Large Population-based Case-Control Study in the San Francisco Bay Area, California Am. J. Epidemiol., November 15, 2007; 166(10): 1174 - 1185. [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]
|
|
|
|
 |
|
 W. Ye, R. Kumar, G. Bacova, J. Lagergren, K. Hemminki, and O. Nyren The XPD 751Gln allele is associated with an increased risk for esophageal adenocarcinoma: a population-based case-control study in Sweden Carcinogenesis, September 1, 2006; 27(9): 1835 - 1841. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Giovannetti, V. Mey, S. Nannizzi, G. Pasqualetti, M. Del Tacca, and R. Danesi Pharmacogenetics of anticancer drug sensitivity in pancreatic cancer. Mol. Cancer Ther., June 1, 2006; 5(6): 1387 - 1395. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. J. Duell, D. P. Casella, R. D. Burk, K. T. Kelsey, and E. A. Holly Inflammation, Genetic Polymorphisms in Proinflammatory Genes TNF-A, RANTES, and CCR5, and Risk of Pancreatic Adenocarcinoma. Cancer Epidemiol. Biomarkers Prev., April 1, 2006; 15(4): 726 - 731. [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]
|
|
|
|
|
|
Z. Zhang, J. Wan, X. Jin, T. Jin, H. Shen, D. Lu, and Z. Xia Genetic Polymorphisms in XRCC1, APE1, ADPRT, XRCC2, and XRCC3 and Risk of Chronic Benzene Poisoning in a Chinese Occupational Population Cancer Epidemiol. Biomarkers Prev., November 1, 2005; 14(11): 2614 - 2619. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Chan, F. Wang, and E. A. Holly Vegetable and Fruit Intake and Pancreatic Cancer in a Population-Based Case-Control Study in the San Francisco Bay Area Cancer Epidemiol. Biomarkers Prev., September 1, 2005; 14(9): 2093 - 2097. [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]
|
|
|
|
|
|
E. J. Duell and E. A. Holly Reproductive and Menstrual Risk Factors for Pancreatic Cancer: A Population-based Study of San Francisco Bay Area Women Am. J. Epidemiol., April 15, 2005; 161(8): 741 - 747. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Ito, K. Matsuo, N. Hamajima, T. Mitsudomi, T. Sugiura, T. Saito, T. Yasue, K.-M. Lee, D. Kang, K.-Y. Yoo, et al. Gene-environment interactions between the smoking habit and polymorphisms in the DNA repair genes, APE1 Asp148Glu and XRCC1 Arg399Gln, in Japanese lung cancer risk Carcinogenesis, August 1, 2004; 25(8): 1395 - 1401. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. H. Wilson and K. Olden The Environmental Genome Project: Phase I and Beyond Mol. Interv., June 1, 2004; 4(3): 147 - 156. [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]
|
|
|
|
|
|
L. Hagmar, U. Stromberg, S. Bonassi, I.-L. Hansteen, L. E. Knudsen, C. Lindholm, and H. Norppa Impact of Types of Lymphocyte Chromosomal Aberrations on Human Cancer Risk: Results from Nordic and Italian Cohorts Cancer Res., March 15, 2004; 64(6): 2258 - 2263. [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]
|
|
|
|
|
|
E. A. Holly, C. A. Eberle, and P. M. Bracci Prior History of Allergies and Pancreatic Cancer in the San Francisco Bay Area Am. J. Epidemiol., September 1, 2003; 158(5): 432 - 441. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Taverna, H.-s. Hwang, J. E. Schupp, T. Radivoyevitch, N. N. Session, G. Reddy, D. A. Zarling, and T. J. Kinsella Inhibition of Base Excision Repair Potentiates Iododeoxyuridine-induced Cytotoxicity and Radiosensitization Cancer Res., February 15, 2003; 63(4): 838 - 846. [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 |
