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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.

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