Biomaterial Database

XRCC1 polymorphism and lung cancer risk in relation to tobacco smoking. 2005

Joachim Schneider, and Vera Classen, and Ulrike Bernges, and Monika Philipp

Institut und Poliklinik für Arbeits- und Sozialmedizin der Justus-Liebig Universität, Aulweg 129/III, D-35385 Giessen, Germany. joachim.schneider@arbmed.med.uni-giessen.de

DNA repair plays a critical role in protecting the genome of the cell from carcinogens or ionising radiation. Reduced DNA-repair capacity can increase susceptibility to occupational-induced cancer. Three coding polymorphisms at codons 194, 280, and 399 in X-ray cross complementing group 1 (XRCC1) DNA-repair gene have been identified, and it is possible that these polymorphisms may affect DNA- repair capacity and thus modulate cancer susceptibility. In the current German study, we investigated the role of XRCC1-polymorphisms as a genetic modifier of risk for individuals with lung cancer as susceptible genotypes, especially in relation to tobacco smoking. Three polymorphisms; XRCC1 Arg194Trp, XRCC1 Arg280His and XRCC1 Arg399Gln, were determined by real-time PCR analysis in 446 lung cancer patients and 622 controls. The observed allele frequencies in the population were within the range described for Caucasians. Multivariate analyses of lung cancer patients who carried at least one mutant variant allele of XRCC1 Arg194Trp (OR=1.03; 95%-CI: 0.66-1.61), XRCC1 Arg280His (OR=0.95; 95%-CI: 0.57-1.60), or XRCC1 Arg399Gln (OR=0.99 CI: 0.73-1.34), did not show any elevated risks. When analysed by histology, no individual subtype of lung cancer was significantly associated with the polymorphisms. Lung cancer risk rose significantly with higher cumulative cigarette consumption. Stratified analysis between tobacco smoking and variant genotypes revealed increasing risks for heavy smokers (>60 pack-years), with the presence of at least one copy of the XRCC1 Arg194Trp variant allele (OR=79.29; 95%-CI: 8.53-737.04) and the XRCC1 Arg399Gln (OR=61.87; 95%-CI: 15.65-244.67). By analysing the interaction between tobacco smoking and the genotypes, combined smoking and having the susceptible genotypes did not show a joint effect. In this study, the XRCC1 Arg194Trp, XRCC1 Arg280His, and XRCC1 Arg399Gln-polymorphisms, had no relevant modifying effect on lung cancer risk and cumulative smoking dose.

UI	MeSH Term	Description	Entries
D008175	Lung Neoplasms	Tumors or cancer of the LUNG.	Cancer of Lung,Lung Cancer,Pulmonary Cancer,Pulmonary Neoplasms,Cancer of the Lung,Neoplasms, Lung,Neoplasms, Pulmonary,Cancer, Lung,Cancer, Pulmonary,Cancers, Lung,Cancers, Pulmonary,Lung Cancers,Lung Neoplasm,Neoplasm, Lung,Neoplasm, Pulmonary,Pulmonary Cancers,Pulmonary Neoplasm
D008297	Male		Males
D008875	Middle Aged	An adult aged 45 - 64 years.	Middle Age
D011110	Polymorphism, Genetic	The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.	Gene Polymorphism,Genetic Polymorphism,Polymorphism (Genetics),Genetic Polymorphisms,Gene Polymorphisms,Polymorphism, Gene,Polymorphisms (Genetics),Polymorphisms, Gene,Polymorphisms, Genetic
D004268	DNA-Binding Proteins	Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.	DNA Helix Destabilizing Proteins,DNA-Binding Protein,Single-Stranded DNA Binding Proteins,DNA Binding Protein,DNA Single-Stranded Binding Protein,SS DNA BP,Single-Stranded DNA-Binding Protein,Binding Protein, DNA,DNA Binding Proteins,DNA Single Stranded Binding Protein,DNA-Binding Protein, Single-Stranded,Protein, DNA-Binding,Single Stranded DNA Binding Protein,Single Stranded DNA Binding Proteins
D005260	Female		Females
D005787	Gene Frequency	The proportion of one particular in the total of all ALLELES for one genetic locus in a breeding POPULATION.	Allele Frequency,Genetic Equilibrium,Equilibrium, Genetic,Allele Frequencies,Frequencies, Allele,Frequencies, Gene,Frequency, Allele,Frequency, Gene,Gene Frequencies
D005838	Genotype	The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.	Genogroup,Genogroups,Genotypes
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000076105	X-ray Repair Cross Complementing Protein 1	A poly(ADP)-ribose-binding protein that functions in the rejoining of DNA single-strand breaks that arise following treatment with alkylating agents or ionizing radiation. It interacts with DNA LIGASE III and POLY ADP RIBOSE POLYMERASE in BASE EXCISION REPAIR, and may also function in DNA processing and chromosome recombination in GERM CELLS.	XRCC1 DNA Repair Protein,XRCC1 Protein,X ray Repair Cross Complementing Protein 1