Correlation between polymorphisms in DNA mismatch repair genes and the risk of primary hepatocellular carcinoma for the Han population in northern China

Liu, Ying; Zhang, Xiaolin; Jia, Jinhai; Tang, Longmei; Gao, Xia; Yan, Lei; Wang, Liqin; Yu, Fei; Ma, Ning; Liu, Wenxuan; Yang, Lei; Li, Xuehui; Liu, Dianwu

doi:10.3109/00365521.2015.1045429

Cited by 11 publications

(10 citation statements)

References 23 publications

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“…Consistent with our results, MSH6 rs1042821 has previously been associated with increased CRC risk [91,92,93], highly malignant bladder cancer [94], pancreatic cancer [95] and triple negative breast cancer (TNBC) [96]. On the contrary, the T allele [97] and the CT heterozygous genotype [98] have been associated with decreased colorectal and hepatocellular carcinoma, respectively. The only meta-analysis concerning the role of MSH6 rs1042821 on cancer predisposition that we are aware of is also inconclusive [99].…”

Section: Discussionsupporting

confidence: 89%

Thyroid Cancer: The Quest for Genetic Susceptibility Involving DNA Repair Genes

Santos

Gomes

Bastos

et al. 2019

Genes

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The incidence of thyroid cancer (TC), particularly well-differentiated forms (DTC), has been rising and remains the highest among endocrine malignancies. Although ionizing radiation (IR) is well established on DTC aetiology, other environmental and genetic factors may also be involved. DNA repair single nucleotide polymorphisms (SNPs) could be among the former, helping in explaining the high incidence. To further clarify the role of DNA repair SNPs in DTC susceptibility, we analyzed 36 SNPs in 27 DNA repair genes in a population of 106 DTCs and corresponding controls with the aim of interpreting joint data from previously studied isolated SNPs in DNA repair genes. Significant associations with DTC susceptibility were observed for XRCC3 rs861539, XPC rs2228001, CCNH rs2230641, MSH6 rs1042821 and ERCC5 rs2227869 and for a haplotype block on chromosome 5q. From 595 SNP-SNP combinations tested and 114 showing relevance, 15 significant SNP combinations (p < 0.01) were detected on paired SNP analysis, most of which involving CCNH rs2230641 and mismatch repair variants. Overall, a gene-dosage effect between the number of risk genotypes and DTC predisposition was observed. In spite of the volume of data presented, new studies are sought to provide an interpretability of the role of SNPs in DNA repair genes and their combinations in DTC susceptibility.

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Section: Discussionsupporting

confidence: 89%

Thyroid Cancer: The Quest for Genetic Susceptibility Involving DNA Repair Genes

Santos

Gomes

Bastos

et al. 2019

Genes

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“…Other studies (50)(51)(52)(53)57), including a recent meta-analysis by Li et al (58), detected a cancer risk reduction in MSH6 rs1042821 heterozygotes or variant allele carriers. It should be noted that these observations in variant allele carriers do not contradict our prior suggestion of risk increase in variant homozygotes: considering, as stated above, i) the dual role of MSH6 on DNA repair and apoptosis; ii) the likely involvement of the MSH6 NTR in the differential regulation of such functions; and iii) the location and potential impact of rs1042821, it is possible that this SNP has distinct effects on each of MSH6 functions (DNA repair or apoptosis signalling) critically impairing one but somehow favouring the other.…”

Section: Discussionmentioning

confidence: 99%

Mismatch repair single nucleotide polymorphisms and thyroid cancer susceptibility

Santos

Silva

et al. 2018

Oncol Lett

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Thyroid cancer (TC) is the most common endocrine malignancy and its incidence continues to rise worldwide. Ionizing radiation exposure is the best established etiological factor. Heritability is high; however, despite valuable contribution from recent genome-wide association studies, the current understanding of genetic susceptibility to TC remains limited. Several studies suggest that altered function or expression of the DNA mismatch repair (MMR) system may contribute to TC pathogenesis. Therefore, the present study aimed to evaluate the potential role of a panel of MMR single nucleotide polymorphisms (SNPs) on the individual susceptibility to well-differentiated TC (DTC). A case-control study was performed involving 106 DTC patients and 212 age- and gender-matched controls, who were all Caucasian Portuguese. Six SNPs present in distinct MMR genes ( rs1799977, rs26279, rs5745325, rs5742933, rs175080 and rs1042821) were genotyped through TaqMan assays and genotype-associated risk estimates were calculated. An increased risk was observed in rs1042821 variant homozygotes [adjusted odds ratio (OR)=3.42, 95% CI: 1.04-11.24, P=0.04, under the co-dominant model; adjusted OR=3.84, 95% CI: 1.18-12.44, P=0.03, under the recessive model]. The association was especially evident for the follicular histotype and female sex. The association was also apparent when was analysed in combination with other MMR SNPs such as rs26279. Interestingly, two other SNP combinations, both containing the heterozygous genotype, were associated with a risk reduction, suggesting a protective effect for these genotype combinations. These data support the idea that MMR SNPs such as rs1042821, alone or in combination, may contribute to DTC susceptibility. This is coherent with the limited evidence available. Nevertheless, further studies are needed to validate these findings and to establish the usefulness of these SNPs as genetic susceptibility biomarkers for DTC so that, in the near future, cancer prevention policies may be optimized under a personalized medicine perspective.

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“…Interestingly, another study described the rs175080 SNP as a variant increasing the risk of lung cancer, but in interaction with other risk factors, such as smoking [ 75 ]. The association between the AA genotype of rs175080 and a higher risk of the primary hepatocellular carcinoma was observed in a Chinese population [ 76 ]. This SNP increased the risk of cervical carcinoma, as assayed for on a Chinese population as well [ 77 ].…”

Section: Results On Mmr Gene Variantsmentioning

confidence: 99%

“…Yi et al found by the yeast two-hybrid assay that the presence of SNP rs2075789 (c.85C>T; Pro29Ser) significantly weakens the interaction of MSH4-MSH5 complex [ 115 ]. The last two studies, which were carried on Chinese populations, revealed that rs707938 increased the risk of hepatocellular carcinoma; rs707939 (c.1326+36C>A) had the negative effect in lung cancer patients, increasing the overall toxicity to platinum-based chemotherapy [ 76 , 116 ]. Recently, the authors investigated the role of DNA repair genes in LC patients by a multilevel association study with 1655 single nucleotide polymorphisms (SNPs) in 211 DNA repair genes on 6911 individuals pooled from four genome-wide case–control studies.…”

Section: Results On Mmr Gene Variantsmentioning

confidence: 99%

“…Despite the fact that this association was especially evident for the follicular histotype and female sex, the outcomes need to be replicated [ 126 ]. Homozygous carriers had a higher risk of CpG island methylated phenotype (CIMP+) in colon cancer (OR = 2.20, 95% CI = 1.10–4.20) than those with WT genotype [ 76 , 124 , 127 , 128 ]. A very significant association with the pancreatic cancer was also found ( p ≤ 0.002) for A/G or A/A genotype [ 129 ].…”

Section: Results On Mmr Gene Variantsmentioning

confidence: 99%

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DNA Mismatch Repair Gene Variants in Sporadic Solid Cancers

Čaja

Vodičková

Král

et al. 2020

IJMS

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The phenotypic effects of single nucleotide polymorphisms (SNPs) in the development of sporadic solid cancers are still scarce. The aim of this review was to summarise and analyse published data on the associations between SNPs in mismatch repair genes and various cancers. The mismatch repair system plays a unique role in the control of the genetic integrity and it is often inactivated (germline and somatic mutations and hypermethylation) in cancer patients. Here, we focused on germline variants in mismatch repair genes and found the outcomes rather controversial: some SNPs are sometimes ascribed as protective, while other studies reported their pathological effects. Regarding the complexity of cancer as one disease, we attempted to ascertain if particular polymorphisms exert the effect in the same direction in the development and treatment of different malignancies, although it is still not straightforward to conclude whether polymorphisms always play a clear positive role or a negative one. Most recent and robust genome-wide studies suggest that risk of cancer is modulated by variants in mismatch repair genes, for example in colorectal cancer. Our study shows that rs1800734 in MLH1 or rs2303428 in MSH2 may influence the development of different malignancies. The lack of functional studies on many DNA mismatch repair SNPs as well as their interactions are not explored yet. Notably, the concerted action of more variants in one individual may be protective or harmful. Further, complex interactions of DNA mismatch repair variations with both the environment and microenvironment in the cancer pathogenesis will deserve further attention.

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Correlation between polymorphisms in DNA mismatch repair genes and the risk of primary hepatocellular carcinoma for the Han population in northern China

Abstract: Our study suggests that polymorphisms in MLH3 (rs175080), MSH3 (rs26279), MSH5 (rs2075789) and MSH6 (rs1042821) may be independent risk factors for PHC.

Cited by 11 publications

References 23 publications

Thyroid Cancer: The Quest for Genetic Susceptibility Involving DNA Repair Genes

Thyroid Cancer: The Quest for Genetic Susceptibility Involving DNA Repair Genes

Mismatch repair single nucleotide polymorphisms and thyroid cancer susceptibility

DNA Mismatch Repair Gene Variants in Sporadic Solid Cancers

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