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Differences in KRAS Mutation Spectrum in Lung Cancer Cases between African Americans and Caucasians after Occupational or Environmental Exposure to Known Carcinogens¹

Departments of Biochemistry and Molecular Biology [J. D. H., A. S., J. E. M., T. W. A.], Pharmacology and Experimental Therapeutics [M. E., M. H., W. L. B.], Public Health and Preventative Medicine [B. G. L., E. T. H. F.], and Pathology [B. R.], Stanley S. Scott Cancer Center [J. D. H., W. L. B., E. T. H. F.], Louisiana State University Health Sciences Center School of Medicine, New Orleans, Louisiana 70112

Elevated mortality rates of lung cancer in the Mississippi River corridor in Louisiana have been clearly documented for the past half-century and rank among the highest in the nation. A population-based case-control study of lung cancer termed Lower Mississippi River Interagency Cancer Study was conducted in southern Louisiana. Lung tumor specimens were collected, isolated by laser capture microdissection, subjected to PCR to amplify KRAS, and sequenced to confirm mutation status and specificity. Of the 116 lung tumors analyzed to date, 32 (27.6%) contained mutations in either codon 12 or 13 of KRAS. This frequency is comparable to that reported in the literature; however, the mutation spectrum was strikingly different. Of the 32 mutations observed, 21 (65.6%) resulted in the inappropriate insertion of cysteine, 6 (18.8%) resulted in the insertion of serine, 3 (9.4%) resulted in the insertion of valine, and 1 (3.1%) each resulted in the insertion of aspartate and alanine. These data indicate that an abnormally high proportion of cysteine (P = 0.010) and serine (P = 0.002) mutations was observed in our sample group versus lung cancers reported in the literature. KRAS mutations were more common in African Americans with an odds ratio of 2.4 (P = 0.048), as were serine mutations, although the latter did not reach statistical significance (odds ratio, 2.6; P = 0.373). No association was found between the observed mutation spectrum and known lung cancer risk factors.

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