April 20, 2005

Contact: Harriet Bull, 272-6794

ALBUQUERQUE , NM - A new study has found that two specific gene variants may play roles in the development of lung cancer.

Base excision repair (BER) is one of many ways in which cells can cope with DNA damage. It has been suggested that genetic variations in DNA repair genes may be associated with DNA repair capacity and cancer risk.

Paul Brennan, of the International Agency for Research on Cancer in Lyon, France, and colleagues examined associations between each of four polymorphisms of BER genes (OGG1 Ser326Cys, XRCC1 Arg194Trp, XRCC1 Arg280His, and XRCC1 Arg399Gln) and lung cancer risk among 2,188 lung cancer patients and 2,198 control subjects without lung cancer. Overall, neither the OGG1 genotype nor the XRCC1 polymorphisms were associated with lung cancer risk. However, subjects who carried the OGG1 Cys/Cys genotype had an increased risk of adenocarcinoma compared with subjects who carried the Ser/Ser genotype, and the XRCC1 Arg194Trp and Arg280His polymorphisms were each associated with a reduced risk of lung cancer among heavy smokers.

In a unique step for a study of gene-environment interactions, the researchers performed statistical tests to determine the probability that their results were true. Based on the results of this analysis, the authors conclude that the subgroup result for the XRCC1 Arg280His polymorphism is likely to be a false-positive result, whereas the findings on OGG1 Ser326Cys and XRCC1 Arg194Trp are likely to represent true associations.

In an editorial, Marianne Berwick, M.D., Ph.D., of the University of New Mexico , and colleagues point out that estimating false-positive reporting probabilities of associations among genetic variants, environmental exposures, and disease can be problematic because the best way to do these calculations remains unclear. The authors describe how well-done meta-analyses or pooled analyses of available studies might be a useful way to obtain the information needed for these calculations.