Abstract
BackgroundColorectal 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.MethodsA 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.ResultsWe 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.ConclusionThe 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.
Highlights
Colorectal cancer (CRC) is the third most diagnosed malignancy worldwide
Though CRC is known as a malignant disease of developed countries, recent studies demonstrate that the healthcare and incident burden is increasing in low and middle income countries during economic development and corresponding changes from traditional to lifestyle influenced by western culture [5]
Controls had no incidences of cancer or clinicopathologies and as expected from the matched study design, mean age and body mass index (BMI) were not statistically different between the CRC cases and controls (p > 0.09) though gender frequencies were statistically different p < 0.001, (Table 2)
Summary
Colorectal cancer (CRC) is the third most diagnosed malignancy worldwide. The etiology of CRC remains elusive and most likely combines environmental and genetic factors. CRC lifestyle risk factors (e.g. increased meat and fat consumption and alcohol and tobacco use) demonstrate further examination of proteins and genetics associated with key digestive tract function. CRC etiology likely includes both somatic genetic and epigenetic aberrations possibly confounded by such lifestyle factors [3, 4]. Though CRC is known as a malignant disease of developed countries, recent studies demonstrate that the healthcare and incident burden is increasing in low and middle income countries during economic development and corresponding changes from traditional to lifestyle influenced by western culture [5]
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