Analysis of 12 variants in the development of gastric and colorectal cancers

Abstract

AIMTo evaluate the relation between 12 polymorphisms and the development of gastric cancer (GC) and colorectal cancer (CRC).METHODSIn this study, we included 125 individuals with GC diagnosis, 66 individuals with CRC diagnosis and 475 cancer-free individuals. All participants resided in the North region of Brazil and authorized the use of their samples. The 12 polymorphisms (in CASP8, CYP2E1, CYP19A1, IL1A, IL4, MDM2, NFKB1, PAR1, TP53, TYMS, UGT1A1 and XRCC1 genes) were genotyped in a single PCR for each individual, followed by fragment analysis. To avoid misinterpretation due to population substructure, we applied a previously developed set of 61 ancestry-informative markers that can also be genotyped by multiplex PCR. The statistical analyses were performed in Structure v.2.3.4, R environment and SPSS v.20.RESULTSAfter statistical analyses with the control of confounding factors, such as genetic ancestry, three markers (rs79071878 in IL4, rs3730485 in MDM2 and rs28362491 in NFKB1) were positively associated with the development of GC. One of these markers (rs28362491) and the marker in the UGT1A1 gene (rs8175347) were positively associated with the development of CRC. Therefore, we investigated whether the joint presence of the deleterious alleles of each marker could affect the development of cancer and we obtained positive results in all analyses. Carriers of the combination of alleles RP1 + DEL (rs79071878 and rs28361491, respectively) are at 10-times greater risk of developing GC than carriers of other combinations. Similarly, carriers of the combination of DEL + RARE (rs283628 and rs8175347) are at about 12-times greater risk of developing CRC than carriers of other combinations.CONCLUSIONThese findings are important for the comprehension of gastric and CRC development, particularly in highly admixed populations, such as the Brazilian population.

Gene Combination of CD44 rs187116, CD133 rs2240688, NF-κB1 rs28362491 and GSTM1 Deletion as a Potential Biomarker in Risk Prediction of Breast Cancer in Lower Northern Thailand

“…This study showed that the *2*2 homozygous genotype (del/del) was associated with a 2 -fold increased risk (p = 0.041) and with the *2 allele was 1.36 increased risk (p = 0.046). This finding is consistent with a previous report that this polymorphism was not only associated with the risk of oral cancer (Chen et al, 2018b), but also with the development of gastric cancer and colorectal cancer (Cavalcante et al, 2017). GSTM1, one of the glutathione-S-transferase gene family, produces the GSTM1 enzyme involved in the detoxification of polycyclic aromatic hydrocarbons and other carcinogens (Strange and Fryer, 1999).…”

Investigation of INDEL variants in apoptosis: the relevance to gastric cancer

“…Indeed, some of these variants have been associated cancer development in a few studies, but not in others. For instance, one of these variants (rs3834129 in CASP8 ) has been previously studied by our research group in other sampling of the same region: we have associated INS/INS genotype of this variant to reduced chances of developing B-cell acute lymphoblastic leukemia [ 27 ], but have not found any association of this variant with GC or colorectal cancer [ 22 ], so that our study corroborates the findings in the latter. Thus, the association of such variants to GC and other types of cancer is still a matter of great discussion.…”

“…Regarding the observed deviation from HWE in the distribution of rs4197 and rs4645982 in case group, no previous studies were found with these markers, but their genotype distribution varies greatly between different populations in 1000 Genomes Project database [ 21 ]. Curiously, their distribution also presented a deviation from HWE in most populations in that database, suggesting that there could be a selective advantage leading to this pattern and/or that the deviation observed here could be due to population substructure, especially considering the relatively recent admixture process in Brazil, as previously observed for other markers in this population [ 7 , 22 ]. As such, it is an expected process in admixed populations, and it could even highlight the potential of these markers.…”

“…For instance, one of these variants (rs3834129 Table 3 Genotypic distribution of the investigated variants for patients with GC in comparison to control group. P-value, OR and 95%CI were obtained with logistic regression adjusted for age, which was done for the genotype as reference in each line (DEL/DEL vs. the other genotypes of that marker, and the same for INS/DEL and INS/INS) in CASP8) has been previously studied by our research group in other sampling of the same region: we have associated INS/INS genotype of this variant to reduced chances of developing B-cell acute lymphoblastic leukemia [27], but have not found any association of this variant with GC or colorectal cancer [22], so that our study corroborates the findings in the latter. Thus, the association of such variants to GC and other types of cancer is still a matter of great discussion.…”

RASAL1 induces to downregulate the SCD1, leading to suppression of cell proliferation in colon cancer via LXRα/SREBP1c pathway

“…Colon cancer ranks third and fourth in the worldwide rankings of cancer incidence and mortality, respectively [1], with more than 1.3 million new cases reported annually and nearly 0.5 million deaths each year [2]. Multiple factors are involved in the occurrence and development of colon cancer, including the activation of oncogenes and inactivation of tumor suppressor genes [3]. Among them, the classical Ras guanosine triphosphate hydrolases (GTPases), H-Ras, K-Ras, and N-Ras, are critical regulators of proliferation, and it is thus not surprising that they represent the most frequently mutated human oncogenes [4].…”