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.

Preoperative blood-routine markers and prognosis of esophageal squamous cell carcinoma: The Fujian prospective investigation of cancer (FIESTA) study

“…First, other blood-routine markers such as mean platelet volume are unavailable in this study. It is widely reorganized that mean platelet volume is superior over platelet count as a marker of platelet function and activation [ 46 , 47 ]. Second, the findings presented in this study cannot be directly extrapolated to the general populations as we only enrolled postoperative patients for esophageal cancer.…”

KRAS Status is Associated with Metabolic Parameters in Metastatic Colorectal Cancer According to Primary Tumour Location

“…Previous studies evaluating association between obesity/MetS and KRAS status have yielded inconclusive results [14][15][16][17][18]. In this study we investigated associations between serum lipid profile, BMI and metabolic factors with KRAS status according to primary tumour location.…”

“…Associations between environmental factors and KRAS status have not been extensively investigated. Only a few studies have reported inconsistent findings regarding associations between BMI/metabolic parameters and KRAS status [14][15][16][17][18].…”

Correlation between expression of epidermal growth factor receptor and adverse reactions after chemotherapy of advanced non-small-cell lung cancer

“…The currently available EGFR-targeted drugs, including EGFR-tyrosine kinase inhibitors and monoclonal antibodies, can augment the activities of corresponding inhibitors and the susceptibility to gefitinib. 24 …”