Polymorphisms of the DNA repair genes XRCC1 and XRCC3 and risk of lung and colorectal cancer: a case-control study in a Southern Italian population.
BACKGROUND
Genetic polymorphisms in DNA repair genes may influence individual variation in DNA repair capacity, which may be associated with a higher risk of developing cancer. Studies on the association between DNA repair gene polymorphisms and lung and colorectal cancer risk appear to be very limited. This study was designed to examine the polymorphisms associated with two DNA repair genes, namely XRCC1 Arg194Trp, XRCC1 Arg399Gln and XRCC3 Thr241Met, and to investigate their role as susceptibility markers for lung and colorectal cancer.


METHODS
A case-control study was conducted including 94 and 109 cases of lung and colorectal cancer, respectively, and 121 hospital-based age- and sex-matched healthy controls to examine the role of XRCC1 and XRCC3 genetic polymorphisms in the context of lung and colorectal cancer risk for a Southern Italian population. Genomic DNA isolated from 5 ml whole blood was used to genotype XRCC1 Arg194Trp, XRCC1 Arg399Gln and XRCC3 Thr241Met by means of polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis.


RESULTS
No differences were observed among the studied groups with regard to the genotype distribution of XRCC1 codon 194 and 399, thus the risk for lung and colorectal cancer did not appear to be significantly influenced by polymorphisms of this gene. Significant differences were observed among the studied groups with regard to the genotype distribution of XRCC3 codon 241. In particular, the XRCC3 241Met allele was associated with an increased risk of lung and colorectal cancer.


CONCLUSIONS
Our results showed no evidence of a relationship between the XRCC1 Arg194Trp and Arg399Gln polymorphisms and the risk of lung and colorectal cancer. On the other hand, they suggested an increased risk in individuals with the XRCC3 Thr241Met polymorphism thus warranting further study to definitively evaluate the role of DNA repair mechanisms in colorectal and lung cancer susceptibility.
Improta
Giuseppina
G
Laboratory of Molecular Oncology, Centro di Riferimento Oncologico Regionale della Basilicata, Istituto di Ricovero e Cura a Carattere Scientifico, Rionero in Vulture, Potenza, Italy.
Sgambato
Alessandro
A
Bianchino
Gabriella
G
Zupa
Angela
A
Grieco
Vitina
V
La Torre
Giuseppe
G
Traficante
Antonio
A
Cittadini
Achille
A
D000367:Age Factors; D000368:Aged; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007558:Italy; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic; D012737:Sex Factors; D000076105:X-ray Repair Cross Complementing Protein 1
D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C110901:X-ray repair cross complementing protein 3; C000619371:XRCC1 protein, human