ASSOCIAÇÃO DOS POLIMORFISMOS DO TIPO INDEL COM O RISCO DE CÂNCER COLORRETAL NA POPULAÇÃO DO RIO GRANDE DO NORTE: ESTUDO DO TIPO CASO - CONTROLE.
Potential biomarkers of susceptibility; Colorectal cancer; INDEL; VNTR
Colorectal cancer (CRC) is the third most common cancer in men and the second in women worldwide. It is known that various types of mutations increase susceptibility to cancer development. However, the influence of insertion-deletion (INDEL) on CRC risk are few studied in the admixed population, such as Brazilian. Furthermore, INDEL in promoter, 3’-UTR, 5’-UTR and introns regions influence the mRNA expression and stability. Thus, this study aimed to perform case-control study to evaluate the association of 14 INDEL and 2 VNTR (Variable Number Tandem Repeat) on genes involved in carcinogenesis pathways (CASP8 [INDEL, rs3834129] SGSM3 [INDEL, rs56228771], CYP2E1 [INDEL, 96 bp], CYP19A1 [INDEL, rs28892005], UGT1A1 [VNTR, rs8175347] HLAG [INDEL, rs371194629] IL1A [INDEL, rs3783553], IL4 [VNTR, rs79071878] NFKB1 [INDEL, rs28362491] MDM2 [INDEL, rs3730485] TP53 [INDELs, rs17878362, and rs17880560] TYMS [INDEL, rs151264360] XRCC1 [INDEL, rs3213239] UCP2 [INDEL, 45 bp], and ACE [INDEL, rs4646994] ) with CRC risk on Rio Grande do Norte population. Moreover, it was also evaluated the relative autosomal ancestry distribution between case and control groups. The genotyping was performed by ABI PRISM 3130 and GeneMapper ID v3.2. The statistical analysis was performed by R v3.1. Regarding the ancestry distribution, the mean African contribution between case and control was significant different (p-value = 0.049). However, when performed multinomial logistic regression analysis, it was not found difference between groups. And regarding the association analysis between the polymorphism and susceptibility to CRC, it was observed that the D allele on IL4 and the I allele on TYMS was associated with increased CRC risk (p-value = 0.001 and p-value = 0.0165, respectively). In this study was also associated that genotype combination of TYMS (rs151264360) and IL4 (rs79071878) might increase CRC risk with at least 3 risk alleles. In summary, this study observed that IL4 and TYMS polymorphism were associated with increase CRC risk. And this is the first study of these polymorphism with CRC on Brazilian population.