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Colorectal cancer (CRC) is the third most common cancer and the second leading cause of death worldwide. Down-regulation of the cysteine-rich reversion-inducing protein with Kazal motifs (RECK) has been confirmed in numerous human cancers and is clinically associated with metastasis. This study aims to explore, for the first time, the possible association of the RECK variants rs11788747 and rs10972727 with CRC susceptibility and clinicopathological features. DNA from 130 CRC patients and 130 healthy blood donors was analyzed. Identification of genetic variants was performed by polymerase chain reactionrestriction fragment length polymorphism (PCR-RFLP) methodology. Association was calculated using the odds ratio (OR) test and P values were adjusted using the Bonferroni test. Individuals carrying the G/G genotype for the rs11788747 variant showed a lower risk of colorectal cancer (OR 0.33; 95% CI 0.16-0.70; P = 0.006). Patients older than 50 years who carry the G/G genotype have a lower risk of CRC (OR 0.26; 95% CI 0.09-0.73; P = 0.019) and of developing advanced tumor-nodule-metastasis (TNM) stages (OR 0.23; 95% CI 0.09-0.54; P = 0.001). Individuals carrying the A/A genotype of the rs10972727 variant also showed decreased risk of CRC (OR 0.38; 95% CI 0.19-0.77; P = 0.011), and were associated with age (over 50 years), sex, advanced TNM stages, and tumor location in the colon. Our results suggest that the RECK variants studied here (rs11788747 and rs10972727) are associated with decreased CRC risk, TNM stages and tumor location. [ABSTRACT FROM AUTHOR]

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 reactionrestriction 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. [ABSTRACT FROM AUTHOR]

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