title: Clinical and metabolic parameters in non-small cell lung carcinoma and colorectal cancer patients with and without KRAS mutations.
abstract: Lung cancer (LC) and colorectal cancer (CRC) are the first and second deadliest types of cancer worldwide. EGFR-based therapy has been used in the treatment of these cancers with variable success. Presence of mutations in the KRAS driver oncogene, possibly induced by environmental factors such as carcinogens in diet and cigarette smoke, may confer worse prognosis and resistance to treatment for reasons not fully understood. Data on possible associations between KRAS mutational status and clinical and metabolic parameters, which may help in clinical management, as well as in identifying risk factors for developing these cancers, are limited in the current literature. We sequenced the KRAS gene and investigated the associations of variations in 108 patients with non-small cell lung carcinoma (NSCLC), the most common form of LC, and in 116 patients with CRC. All of the mutations originated from the guanosine nucleotide and over half of all transversions in NSCLC and CRC were c.34 G>T and c.35 G>T, respectively. c.35 G>A was the most frequent type of transition in both cancers. Excluding smoking, the clinical and metabolic parameters in patients carrying mutant and wild type KRAS were similar except that the CRC patients with transversion mutations were 8.6 years younger than those carrying the transitions (P < 0.01). Dyslipidemia, hypertension, family cancer history, and age of diagnosis older than 60 years were more frequent in NSCLC than CRC (P ≤ 0.04). These results suggest that most of the clinical and metabolic parameters investigated in this study are probably not associated with the more aggressive phenotype and differences in response to EGFR-based treatment previously reported in patients with KRAS mutations. However, the increased rates of abnormal metabolic parameters in patients with NSCLC in comparison to CRC indicate that these parameters may be more important in the management of NSCLC. CRC patients carrying transition mutations are older than those carrying transversions, suggesting that age may determine the type of KRAS mutation in CRC patients.
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, OH 43210, USA. Ahmet.Yilmaz2@osumc.edu.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Yilmaz
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, OH 43210, USA. Nehad.Mohamed@osumc.edu.
authors.forename: Nehad
authors.initials: N
authors.lastname: Mohamed
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, OH 43210, USA. Kara.Patterson@osumc.edu.
authors.forename: Kara A
authors.initials: KA
authors.lastname: Patterson
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, OH 43210, USA. Yan.Tang@osumc.edu.
authors.forename: Yan
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, OH 43210, USA. Konstantin.Shilo@osumc.edu.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Shilo
authors.affiliation: Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA. Miguel.Villalona@osumc.edu.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Villalona-Calero
authors.affiliation: Department of Animal Sciences, The Ohio State University, Columbus, OH 43210, USA. Davis.28@osu.edu.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Davis
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, OH 43210, USA. Xiao-Ping.Zhou@osumc.edu.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Zhou
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, OH 43210, USA. Wendy.Frankel@osumc.edu.
authors.forename: Wendy
authors.initials: W
authors.lastname: Frankel
authors.affiliation: Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA. Greg.Otterson@osumc.edu.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Otterson
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, OH 43210, USA. Weiqiang.Zhao@osumc.edu.
authors.forename: Weiqiang
authors.initials: W
authors.lastname: Zhao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000453:epidemiology / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins