Western influenced lifestyle and Kv2.1 association as predicted biomarkers for Tunisian colorectal cancer.
Western influenced lifestyle and Kv2.1 association as predicted biomarkers for Tunisian colorectal cancer.
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DOI：
10.1186/s12885-020-07605-7
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发表时间：
2020-11-10
期刊：
影响因子：
3.8
通讯作者：
Bouhaouala-Zahar B
中科院分区：
文献类型：
--
作者：
Barbirou M;Woldu HG;Sghaier I;Bedoui SA;Mokrani A;Aami R;Mezlini A;Yacoubi-Loueslati B;Tonellato PJ;Bouhaouala-Zahar B
结直肠癌（CRC）是全球第三大确诊恶性肿瘤。随着行为和生活方式的持续西化，全球负担预计将增加。结直肠癌的病因仍然难以捉摸，很可能是环境和遗传因素共同作用的结果。 KCNB1编码的Kv2.1钾通道在癌症恶性肿瘤中发挥多种作用，可能是结直肠癌易感性的关键因素。我们的研究提供了突尼斯 CRC 与 KCNB1 变异和生活方式因素之间相互作用之间的基线关联。进行了一项涉及 300 名 CRC 患者和 300 名对照的病例对照研究，对患者进行了仔细的表型分析并随访直至研究结束。 KCNB1 基因分型通过 Sanger 测序得到证实。使用双变量和多变量逻辑回归分析来评估与 CRC 相关的临床状态、生活方式和研究多态性。我们注意到性别与结直肠癌的发生有显着相关性。此外，大量肉类和脂肪摄入、饮酒和体力活动 (PA) 会增加结直肠癌风险。 rs1051296 A/G 和 rs11468831 ins/del 和 del/del 基因型的携带 (p<0.001) 与 CRC 风险显着相关。根据性别的分析显示，无论患者性别如何，rs1051295 A/G、rs11468831 non ins/ins (p = 0.01) 与 CRC 易感性相关，而 rs3331 T/C (p = 0.012) 与女性相关。根据恶性肿瘤部位进行分层研究；直肠癌 (RC) 和结肠癌 (CC) 揭示了性别、高肉类和脂肪摄入、饮酒和 PA 导致 RC 风险的增加。然而，CC 还与高盐水消耗量存在额外关联。 rs1051295 A/G (p = 0.01) 与 RC 风险相关。 CC 风险增加与携带 rs1051295 A/G、rs11168831 (del/del) 和 (ins/del) 基因型相关。结直肠癌的风险随着西方生活方式对突尼斯人生活方式影响的可改变因素而增加，例如饮酒、高脂肪消耗和可能的蔬菜摄入不足。此外，KCNB1多态性也显着影响CRC的易感性。我们的研究建立了与突尼斯 CRC 相关的临床状态、西方影响的生活方式和 KCNB1 变异的基线特征的关键要素。
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. 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. 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. 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.