Jiang Qiang-Hua, Peng Hong-Xin, Zhang Yi, Tian Peng, Xi Zu-Lian, Chen Hao
Department of Surgery, Dongyang People's Hospital, Dongyang, Zhejiang, People's Republic of China.
Medical College, Southeast University, Nanjing, Jiangsu, People's Republic of China ; Central Laboratory, Nanjing First Hospital, Nanjing, Jiangsu, People's Republic of China.
Onco Targets Ther. 2015 Oct 22;8:3041-5. doi: 10.2147/OTT.S89746. eCollection 2015.
rs712 within 3'-untranslated region of KRAS can affect the specific binding between the mRNA and its targeted microRNAs, leading to the activation of KRAS oncogene. However, the possible association between the locus and susceptibility to colorectal cancer (CRC) remains unclear. We investigated genotypes of the locus in 586 cases and 476 controls to explore the possible association between them. Results of our case-control study showed that genotypes TT (6.5% vs 2.5%, P=0.002, adjusted odds ratio [OR] =2.810, 95% confidence interval [CI] =1.342-5.488) and GT/TT (36.5% vs 30.5%, P=0.038, adjusted OR =1.342, 95% CI =1.030-1.712) and allele T (21.5% vs 6.5%, P=0.004, adjusted OR =1.328, 95% CI =1.105-1.722) of rs712 were significantly associated with an increased risk of CRC, and the significant association was also observed in the recessive model (TT vs GG/GT, 6.5% vs 2.5%, P=0.003, adjusted OR =0.372, 95% CI =0.191-0.725). However, there was no association between genotype GT and risk of CRC (30.0% vs 28.0%, P=0.235, adjusted OR =1.210, 95% CI =0.903-1.548). Furthermore, genotype GT (P=0.003) and allele T (P=0.003) were significantly associated with poor differentiation, and genotypes GT and TT and allele T were significantly associated with tumor-node-metastases stage III (P=0.001 for GT vs GG, P<0.001 for TT vs GG, and P<0.001 for T vs G) and node metastasis (P<0.001 for GT vs GG, P=0.001 for TT vs GG, and P<0.001 for T vs G), respectively. These findings indicated that allele T and genotypes TT and GT/TT of rs712 might be susceptible factors for CRC, and mutated allele and genotypes of the locus might predict a poor clinical outcome in Chinese population.
KRAS基因3'非翻译区内的rs712可影响mRNA与其靶向微小RNA之间的特异性结合,从而导致KRAS癌基因激活。然而,该位点与结直肠癌(CRC)易感性之间的潜在关联仍不明确。我们调查了586例病例和476例对照中该位点的基因型,以探讨它们之间的潜在关联。我们的病例对照研究结果显示,rs712的基因型TT(6.5%对2.5%,P = 0.002,调整后的优势比[OR] = 2.810,95%置信区间[CI] = 1.342 - 5.488)、GT/TT(36.5%对30.5%,P = 0.038,调整后的OR = 1.342,95% CI = 1.030 - 1.712)以及等位基因T(21.5%对6.5%,P = 0.004,调整后的OR = 1.328,95% CI = 1.105 - 1.722)与CRC风险增加显著相关,并且在隐性模型中也观察到显著关联(TT对GG/GT,6.5%对2.5%,P = 0.003,调整后的OR = 0.372,95% CI = 0.191 - 0.725)。然而,基因型GT与CRC风险之间无关联(30.0%对28.0%,P = 0.235,调整后的OR = 1.210,95% CI = 0.903 - 1.548)。此外,基因型GT(P = 0.003)和等位基因T(P = 0.003)与低分化显著相关,基因型GT、TT以及等位基因T分别与肿瘤-淋巴结-转移III期(GT对GG,P = 0.001;TT对GG,P < 0.001;T对G,P < 0.001)和淋巴结转移(GT对GG,P < 0.001;TT对GG,P = 0.001;T对G,P < 0.001)显著相关。这些发现表明,rs712的等位基因T以及基因型TT和GT/TT可能是CRC的易感因素,并且该位点的突变等位基因和基因型可能预示着中国人群不良的临床结局。