SMAD7 Variant rs4939827 Is Associated with Colorectal Cancer Risk in Croatian Population

Kirac, Iva; Matošević, Petar; Augustin, Goran; Šimunović, Iva; Hostić, Vedran; Župančić, Sven; Hayward, Caroline; Antoljak, Nataša; Rudan, Igor; Campbell, Harry; Dunlop, Malcolm G.; Vrdoljak, Danko Velimir; Kovačević, Dujo; Zgaga, Lina

doi:10.1371/journal.pone.0074042

Cited by 11 publications

(10 citation statements)

References 27 publications

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“…For example, SMAD7 rs4939827 was found to be associated with CRC in two GWASs [ 74 , 75 ]. The association of SMAD7 rs4939827 with CRC was confirmed by other replication studies [ 76 , 77 ]. A summary of other SNPs studied as risk factors for CRC is shown in Table 8 .…”

Section: Genome-wide Association Study and Colorectal Cancersupporting

confidence: 69%

Single Nucleotide Polymorphism in SMAD7 and CHI3L1 and Colorectal Cancer Risk

El-Fattah

Sadik

Shaker

et al. 2018

Mediators of Inflammation

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Colorectal cancer (CRC) is one of the leading cancers throughout the world. It represents the third most common cancer and the fourth in mortality. Most of CRC are sporadic, arise with no known high-penetrant genetic variation and with no previous family history. The etiology of sporadic CRC is considered to be multifactorial and arises from the interaction of genetic variants of low-penetrant genes and environmental risk factors. The most common well-studied genetic variation is single nucleotide polymorphisms (SNPs). SNP arises as a point mutation. If the frequency of the sequence variation reaches 1% or more in the population, it is referred to as polymorphism, but if it is lower than 1%, the allele is typically considered as a mutation. Lots of SNPs have been associated with CRC development and progression, for example, genes of TGF-β1 and CHI3L1 pathways. TGF-β1 is a pleiotropic cytokine with a dual role in cancer development and progression. TGF-β1 mediates its actions through canonical and noncanonical pathways. The most important negative regulatory protein for TGF-β1 activity is termed SMAD7. The production of TGF-β can be controlled by another protein called YKL-40. YKL-40 is a glycoprotein with an important role in cancer initiation and metastasis. YKL-40 is encoded by the CHI3L1 gene. The aim of the present review is to give a brief introduction of CRC, SNP, and examples of some SNPs that have been documented to be associated with CRC. We also discuss two important signaling pathways TGF-β1 and CHI3L1 that influence the incidence and progression of CRC.

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Section: Genome-wide Association Study and Colorectal Cancersupporting

confidence: 69%

Single Nucleotide Polymorphism in SMAD7 and CHI3L1 and Colorectal Cancer Risk

El-Fattah

Sadik

Shaker

et al. 2018

Mediators of Inflammation

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“… 22 Another study revealed the association between SNP of rs4939827 and the risk of CRC in the Croatian population. 36 Rs4464148, located in intron 3 of SMAD7 gene, has also been discovered to be correlated with the risk of CRC in European-ancestry populations. 55 Besides that, Rs4464148 variant genotype of SMAD7 has been proved to be associated with an increased cancer incidence.…”

Section: Discussionmentioning

confidence: 99%

Correlation Between CASC8, SMAD7 Polymorphisms and the Susceptibility to Colorectal Cancer

et al. 2015

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Genome-wide association studies (GWASs) and a number of case–control studies have suggested that several single nucleotide polymorphisms (SNPs), rs7837328, rs7014346, rs6983267, rs10505477 on CASC8 gene and rs4939827, rs4464148, rs12953717 on SMAD7 gene are significantly correlated with the susceptibility to colorectal cancer (CRC). For the sake of clarifying the association, a meta-analysis was conducted and population heterogeneity was considered in the study.A total of 34 articles including 90 studies (168,471 cases and 163,223 controls) that evaluated the relationship between the CASC8, SMAD7 genes and the risk of CRC under the allelic model were reviewed. Also subgroup analysis was performed by ethnicity (Caucasian, Asian, and African) and all of the analyses were implemented in R 3.2.1 software.Pooled data from the meta-analysis revealed that the A allele of rs7837328, the A allele of rs7014346, the G allele of rs6983267, the A allele of rs10505477, the T allele of rs4939827, the T of rs4464148, and the T of rs12953717 were significantly associated with an increased risk of CRC under the allelic model. Additionally, subgroup analyses of 6 SNPs by ethnicity (rs4464148 excepted) witnessed that the A allele of rs7837328, the G allele of rs6983267, and the T of rs12953717 were notably associated with an increased risk of CRC among Caucasian and Asian. Furthermore, the A allele of rs7014346, the A allele of rs10505477, and the T allele of rs4939827 were significantly related with an elevated risk of CRC only among Caucasian.Our study suggested that for CASC8 gene, SNP of rs7837328 and rs6983267 are risk factors for CRC among both Caucasian and Asian whereas rs7014346 and rs10505477 are risky gene polymorphisms only among Caucasian. For SMAD7 gene, rs4939827 and rs4464148 are risk factors for CRC among Caucasian whereas rs12953717 could elevate the susceptibility to CRC in both Caucasian and Asian.

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“…The involvement of these SNPs in the occurrence of CRC may vary between populations, for example, due to allele frequencies or particular genetic and environmental factors that may modify the effect of the variants. Recognizing the effects in different populations may help in discovering disease mechanism …”

Section: Discussionmentioning

confidence: 99%

Impact of microRNA‐375 and its target gene SMAD‐7 polymorphism on susceptibility of colorectal cancer

Shaker

Mohammed

et al. 2017

Clinical Laboratory Analysis

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Background Colorectal cancer (CRC) has a high morbidity and mortality. Many studies reported that mir‐375 is frequently down‐regulated in many cancers including esophageal cancer, hepatocellular carcinoma, breast cancer and leukemias. Aim Our aim was to study the expression of microRNA‐375 and its target gene SMAD‐7 polymorphisms (rs4939827) in CRC patients in comparison to control subjects and to correlate these results with clinical data of patients to elucidate their role in pathogenesis and early diagnosis of CRC. Material and methods The present study was conducted on 122 subjects divided into 86 patients with CRC and 36 age‐ and sex‐matched controls. The followings were done to all subjects: full history taking, full clinical examination, complete blood picture, serum (ALT, AST), serum albumin, CEA, TLC, PLT, and creatinine. Gene expression of miRNA‐375 from serum was done by real‐time PCR. Gene polymorphism SNPs of SMAD7 (rs4939827) was also done in DNA extracted from blood by real‐time PCR. Results As regards the polymorphism of SMAD7, we found that CC (wild) genotype has high percentage in controls compared to CRC cases (36.1% vs 15.1%). Meanwhile, the mutant and heterozygotes genotypes showed high percentage among cases compared to controls (33.7%, and 51.2% respectively) vs (22.2%, and 41.7% respectively) with no significant statistical analysis. There was a statistically significant high T‐allelic frequency among cases and C‐allelic frequency among controls. There was a statistically significant association between fold change in micro RNA (‐375) and the susceptibility to CRC as there is down‐regulation of the microRNA‐375 in CRC group with fold change in 0.42±0.27. Conclusion Micro RNA‐375 and rs4939827 SNP in SMAD7 could be considered as potential markers for detecting and early diagnosing CRC patients.

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SMAD7 Variant rs4939827 Is Associated with Colorectal Cancer Risk in Croatian Population

Cited by 11 publications

References 27 publications

Single Nucleotide Polymorphism in SMAD7 and CHI3L1 and Colorectal Cancer Risk

Single Nucleotide Polymorphism in SMAD7 and CHI3L1 and Colorectal Cancer Risk

Correlation Between CASC8, SMAD7 Polymorphisms and the Susceptibility to Colorectal Cancer

Impact of microRNA‐375 and its target gene SMAD‐7 polymorphism on susceptibility of colorectal cancer

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