We previously reported an association between increased risk for lung adenocarcinoma and the XRCC1 399Gln allele in non-Hispanic whites (NHW) but not in Hispanics. In the present study we have expanded our population to examine the distribution of the XRCC1, 194, 280 and 399 alleles as well as the OGG1 allele in cases and controls from NHWs and Hispanics. The OGG1 gene encodes an 8-oxoguanine-DNA glycosylase protein key to repairing oxidative damage especially 8-oxo-guanine. Both XRCC1 and OGG1 are involved in the base excision repair (BER) pathway and have recently been reported to interact both physically and functionally. At present, we have analyzed a total of 267 individuals with lung adenocarcinoma (196 NHWs, 56 Hispanics and 15 individuals of other racial descent) and 411 controls (258 NHWs, 135 Hispanics, and 18 individuals of other racial descent). Results indicate that the XRCC1 194 allele may be protective in Hispanics (OR = 0.4; CI = 0.14 - 1.14), while both the XRCC1 280 (OR = 1.9; CI = 1.01 - 3.50) and XRCC1 399 (OR = 1.6; CI = 0.90 - 2.65) alleles are associated with increased risk for lung adenocarcinoma in NHWs, but not Hispanics. The hOGG1 326Ser allele is associated with decreased risk of lung adenocarcinoma in non-Hispanic Whites (OR = 0.63; CI = 0.41 - 0.97). These results suggest that genetic polymorphisms of the XRCC1 and OGG1 DNA repair genes may modulate lung cancer risk differentially depending on ethnicity. Current studies are increasing the sample size in order to refine risk estimates and allow examination of other covariates and gene - gene interactions. Supported by Grants NIEHS ES08801, ES05836 and NIH CA097356.
[Proc Amer Assoc Cancer Res, Volume 46, 2005]