Western influenced lifestyle and Kv2.1 association as predicted biomarkers for Tunisian colorectal cancer

Abstract

Background Colorectal cancer (CRC) is the third most diagnosed malignancy worldwide. The global burden is expected to increase along with ongoing westernized behaviors and lifestyle. The etiology of CRC remains elusive and most likely combines environmental and genetic factors. The Kv2.1 potassium channel encoded by KCNB1 plays a collection of roles in malignancy of cancer and may be a key factor of CRC susceptibility. Our study provides baseline association between Tunisian CRC and interactions between KCNB1 variants and lifestyle factors. Methods A case-control study involving 300 CRC patients, and 300 controls was conducted Patients were carefully phenotyped and followed till the end of study. KCNB1 genotyping was confirmed by Sanger sequencing. Bivariate and multivariable logistic regression analyses were used to assess the clinical status, lifestyle and study polymorphisms association with CRC. Results We noted significant gender association with CRC occurrence. Moreover, CRC risk increases with high meat and fat consumption, alcohol use and physical activity (PA). Carriage of rs1051296 A/G and both rs11468831 ins/del and del/del genotypes (p < 0.001) were significantly associated with CRC risk. Analysis according to gender reveals correlation of rs1051295 A/G, rs11468831 non ins/ins (p = 0.01) with CRC susceptibility regardless of patients’ gender while rs3331 T/C (p = 0.012) was associated with females. Stratification study according to malignancy site; Rectal Cancer (RC) and Colon Cancer (CC), reveals increasing RC risk by gender and high meat and fat consumption, alcohol use and PA. However, additional association with high brine consumption was noted for CC. The rs1051295 A/G (p = 0.01) was associated with RC risk. Increased CC risk was associated with carriage of rs1051295 A/G, rs11168831 (del/del) and (ins/del) genotypes. Conclusion The risk of CRC increases with modifiable factors by Western influences on Tunisian lifestyle such as alcohol use, high fat consumption and possibly inadequate intake of vegetables. In addition, KCNB1 polymorphisms also markedly influence CRC susceptibility. Our study establishes key elements of a baseline characterization of clinical state, Western influenced lifestyle and KCNB1 variants associated with Tunisian CRC.

A Genome-Wide Profiling of Glioma Patients with an IDH1 Mutation Using the Catalogue of Somatic Mutations in Cancer Database

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Molecular Mechanisms of Tumor Immunomodulation in the Microenvironment of Colorectal Cancer

“…Both the tumor characteristics and the patient conditions affect the composition of the TME, subsequently dictating disease progression, responsiveness to cancer treatments and survival prognosis. Indeed, the primary tumor’s specific genetic and epigenetic alterations, its localization (i.e., ascending, transverse or descending colon, or rectum) and the hosting organs in case of metastasis strongly impact the composition of the TME [ 19 , 20 , 21 ]. Furthermore, the patient’s genetic pre-disposition, co-morbidities, bowel pre-conditions (e.g., inflammatory bowel diseases) or lifestyle (e.g., diet, physical activities, smoking) similarly alter the TME [ 22 ].…”

The National Burden of Colorectal Cancer in the United States from 1990 to 2019

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