Clinical and metabolic parameters in non-small cell lung carcinoma and colorectal cancer patients with and without KRAS mutations.

Ahmet Yilmaz,Michael Davis,Miguel Villalona-Calero,Wendy Frankel,Kara Patterson,Yan Tang,Weiqiang Zhao,Konstantin Shilo,Xiao-Ping Zhou,Nehad Mohamed,Gregory Otterson

doi:10.3390/ijerph110908645

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.

Highlights

Lung cancer (LC) and colorectal cancer (CRC), the first and second deadliest types of cancer, are responsible for over 22% of all cancer deaths worldwide [1,2]
Smoking was more frequent in non-small cell lung carcinoma (NSCLC) patients carrying mutated than those carrying the wild type
We compared the parameters in patients carrying different types of KRAS mutations to investigate whether these parameters were related to the type of mutations (Table 2)

Summary

Introduction

Lung cancer (LC) and colorectal cancer (CRC), the first and second deadliest types of cancer, are responsible for over 22% of all cancer deaths worldwide [1,2]. Mutations in KRAS, possibly induced by environmental factors, such as cigarette smoke in LC and diet in CRC, have been reported frequently [3,4]. GTPase that activates proteins such as RAF, MEK, and ERK1/2 involved in the MAPK/ERK signal transduction pathway in response to extracellular signals received by the EGFR [5,6]. It is known that carcinogens in cigarette smoke and Fe++ in red meat directly cause mutations in KRAS [11,12]. Smoking and unhealthy dietary habits are associated with abnormal metabolic parameters such as dyslipidemia, hypertension, and presence of diabetes mellitus either directly due to exposure of cells to mutagens or indirectly via obesity-related hormonal changes [13]

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