Molecular Medicine Division, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS).
Research Unit of Metabolic Diseases, Pediatric UMAE, Instituto Mexicano del Seguro Social (IMSS).
Tohoku J Exp Med. 2020 Feb;250(2):109-119. doi: 10.1620/tjem.250.109.
Colorectal cancer is the third cause of cancer and the second leading cause of death worldwide. The CD44 gene plays a key role in malignant processes, including growth, survival, epithelial to mesenchymal transition and metastasis. It is also known that some variants as rs187116 (c.67+4883G>A) and rs7116432 (c.2024+779A>G) can modulate the function of the CD44 gene and malignant transformation in several neoplasms. This study aims to explore, for the first time, the association of the CD44 rs187116 and rs7116432 variants in patients with colorectal cancer. Genomic DNA from 250 patients and 250 healthy blood donors were analyzed. The identification of variants was made by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Association was calculated by the odds ratio (OR) test and multivariate analysis. Individuals carrying the G/A and A/A genotypes for the rs187116 polymorphism showed an increased risk for colorectal cancer (OR = 3.11, 95% CI: 1.87-5.16, P = 0.001 and OR = 3.59, 95% CI: 2.06-6.25, P = 0.001, respectively). After adjusting for age and gender, these same genotypes and the G/G genotype of the rs7116432 polymorphism were associated with TNM stage and tumor location in the colon. Moreover, the A-G (rs187116 and rs7116432) haplotype was associated with increased risk; while, the haplotype G-A (rs187116 and rs7116432) was related with decreased risk. In conclusion, our results suggest that the here analyzed CD44 variants are involved with risk, TNM stage and tumor location in colorectal cancer.
结直肠癌是全球癌症发病率的第三位和死亡率的第二位病因。CD44 基因在包括生长、存活、上皮间质转化和转移在内的恶性过程中起着关键作用。已知某些变体，如 rs187116（c.67+4883G>A）和 rs7116432（c.2024+779A>G），可以调节 CD44 基因的功能，并在多种肿瘤中促进恶性转化。本研究首次旨在探讨 CD44 rs187116 和 rs7116432 变体与结直肠癌患者的相关性。分析了 250 例患者和 250 例健康献血者的基因组 DNA。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法鉴定变体。通过优势比（OR）检验和多变量分析计算相关性。携带 rs187116 多态性的 G/A 和 A/A 基因型的个体患结直肠癌的风险增加（OR=3.11，95%CI：1.87-5.16，P=0.001 和 OR=3.59，95%CI：2.06-6.25，P=0.001）。在校正年龄和性别后，这些相同的基因型和 rs7116432 多态性的 G/G 基因型与 TNM 分期和肿瘤在结肠中的位置相关。此外，A-G（rs187116 和 rs7116432）单倍型与风险增加相关；而 G-A（rs187116 和 rs7116432）单倍型与风险降低相关。总之，我们的结果表明，这里分析的 CD44 变体与结直肠癌的风险、TNM 分期和肿瘤位置有关。
