Differences in KRAS mutation spectrum in lung cancer cases between African Americans and Caucasians after occupational or environmental exposure to known carcinogens.
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.
Hunt
Jay D
JD
Department of Biochemistry and Molecular Biology, Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center School of Medicine, New Orleans, Louisiana 70112. jhunt@lsuhsc.edu
Strimas
Anna
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Martin
Julie E
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Eyer
Marilyn
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Haddican
Monica
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Luckett
Brian G
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Ruiz
Bernardo
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Axelrad
T William
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Backes
Wayne L
WL
Fontham
Elizabeth T H
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D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D044383:Black People; D002273:Carcinogens / Q000633:toxicity*; D016022:Case-Control Studies; D003062:Codon / Q000187:drug effects / Q000235:genetics; D004781:Environmental Exposure / Q000009:adverse effects*; D019317:Evidence-Based Medicine; D005260:Female; D006801:Humans; D008145:Louisiana / Q000208:ethnology; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000208:ethnology* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects*; D017354:Point Mutation / Q000187:drug effects* / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000187:drug effects / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000187:drug effects* / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D017422:Sequence Analysis, DNA; D013057:Spectrum Analysis; D044465:White People; D018631:ras Proteins; D001741:Black or African American
D014408:Biomarkers, Tumor; D002273:Carcinogens; D003062:Codon; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins