The rs41291957 polymorphism of miR-143/145 and cancer risk: a case-control study and meta-analysis.

Recently, the rs41291957 polymorphism in the promoter region of miR-143/145 has been repeatedly investigated for its contribution to cancer susceptibility. However, the results remain conflicting rather than conclusive, which calls for further investigations. Therefore, we here conducted a case-control study and meta-analysis to explore the association between rs41291957 and cancer risk. In the case-control study, a total of 2277 cancer patients (lung, liver, gastric and colorectal cancers) and 800 normal controls were recruited, the genotyping of rs41291957 was performed with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Sanger sequencing. In the meta-analysis, 5 previously published studies and our present study were included, the STATA 14.0 software was applied to conduct all statistical analyses. The results of case-control study showed that rs41291957 was significantly associated with the risk of gastric cancer, colon cancer, rectal cancer, and colorectal cancer in Hubei Han Chinese population. The results of meta-analysis demonstrated that rs41291957 was significantly associated with overall cancer risk, especially colorectal cancer risk and lung cancer risk. Collectively, the rs41291957 polymorphism of miR-143/145 may be a plausible susceptible locus for cancer risk, which should be validated in future studies with larger samples in different ethnic populations.

The contribution of MALAT1 gene rs3200401 and MEG3 gene rs7158663 to the risk of lung, colorectal, gastric and liver cancer.

Previous studies have repeatedly investigated the effects of MALAT1 gene rs3200401 and MEG3 gene rs7158663 on cancer risk. However, their results remain conflicting rather than conclusive. Therefore, we here performed a case-control study and a followed meta-analysis to examine their contribution to the risk of lung, colorectal, gastric and liver cancer. 550 lung cancer patients, 787 colorectal cancer patients, 460 gastric cancer patients, 480 liver cancer patients and 800 normal controls were included. The genotyping of rs3200401 and rs7158663 was applied with Sanger sequencing technology. Our case-control study revealed that in Hubei Chinese population, rs3200401 was significantly associated with the risk of gastric cancer but not lung, colorectal, or liver cancer, rs7158663 was significantly associated with the risk of gastric and colorectal cancer but not lung or liver cancer. The followed meta-analysis, combining the data of previous studies and present study, showed that rs3200401 was significantly associated with the risk of gastric and colorectal cancer in the pooled population but not liver cancer in Chinese population, rs7158663 was significantly associated with the risk of lung, colorectal and gastric but not liver cancer in Chinese population. Collectively, MALAT1 gene rs3200401 may be a susceptive factor for the development of colorectal and gastric cancer, and MEG3 gene rs7158663 may be a susceptive factor for the development of lung, colorectal and gastric cancer. However, the findings should be validated in future studies with larger sample sizes of different ethnic populations.

The IL-22 gene rs2227478 polymorphism significantly decreases the risk of colorectal cancer in a Han Chinese population.

To examine the role of IL-22 gene in colorectal cancer (CRC) susceptibility, we identified causative genetic polymorphisms in promoter region of IL-22 gene and explored the mechanism underlying their contribution to CRC development in a Chinese population of Hubei province. 13 target single nucleotide polymorphisms (SNPs) in IL-22 gene promoter were genotyped in 787 CRC patients (426 colon cancer and 361 rectal cancer) and 800 normal controls. The results demonstrated that the rs2227478 T > C polymorphism was significantly associated with the risk of colon cancer, rectal cancer and CRC, and the C allele was associated with a decreased cancer risk than the T allele. In CRC tissue samples, the subjects with CT+CC genotypes of rs2227478 had lower levels of IL-22 mRNA than the subjects with TT genotypes. Further functional analysis revealed that the transcription repressor Sp1 possessed a higher binding affinity to the C allele than the T allele. Collectively, the rs2227478 T > C is a functional genetic polymorphism that significantly reduces the CRC risk in a Han Chinese population.

Lack of association between interleukin-22 gene polymorphisms and cancer risk: a case-control study and a meta-analysis.

BACKGROUND: Interleukin-22 (IL22) has been implicated in inflammation and tumorigenesis. The association between IL22 gene polymorphisms and cancer risk has been widely explored. However, the limited sample sizes of previous studies may produce inadequate statistical power and conflicting results, which calls for further investigations. In this study, we recruited a total of 1490 cancer patients (480 liver cancer patients, 550 lung cancer patients, and 460 gastric cancer patients) and 800 normal controls to explore the associations between IL22 gene polymorphisms (rs1179251, rs2227485, rs2227511, and rs2227473) and cancer risk. METHOD: The genotyping was performed with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Sanger sequencing. RESULTS: Our results showed that none of the four IL22 gene polymorphisms was associated with the risk of liver, lung or gastric cancer in Hubei Han Chinese population. To improve the statistical strength, a meta-analysis was further conducted. The results further confirmed our present findings and showed that rs1179251, rs2227485, and rs2227473 were not associated with cancer risk in total or stratified analysis. CONCLUSION: Consequently, the rs1179251, rs2227485, rs2227511, and rs2227473 polymorphisms may not be associated with cancer risk. However, further investigations using larger samples in different ethnic populations are required.

Association study between CYP24A1 gene polymorphisms and cancer risk.

CYP24A1, an essential gene in regulation of vitamin D, has been reported to play an important role in enhancing immune activity and inhibiting tumorigenesis. Previous studies proposed that rs2585428, rs4809960, rs6022999 and rs6068816 in CYP24A1 gene might be greatly associated with cancer risk. To validate the findings, we here investigated the associations of these four polymorphisms and colorectal cancer (CRC) risk in a central Chinese population (426 colon cancer patients, 361 rectal cancer patients and 800 healthy controls). The genotyping was conducted by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and confirmed by sequencing. Our results revealed that the rs4809960 and rs6022999 were strongly associated with the CRC risk, especially with the colon cancer risk. Moreover, the analysis of haplotypes consisting of rs2585428(G > A), rs4809960(T > C), rs6022999(A > G) and rs6068816(C > T) indicated that haplotype ATGC significantly decreased the CRC risk, especially the colon cancer risk. Haplotype GCAT significantly increased the CRC risk, especially the rectal cancer risk. However, haplotype ACAC was only found to be associated with increased risk of CRC. To improve the statistical strength, an updated meta-analysis was further performed. The results showed that rs2585428 was associated with cancer risk in Caucasian population, rs4809960 was associated with breast cancer risk in Caucasian population, and rs6022999 was associated with cancer risk in Asian population. Collectively, the rs4809960 and rs6022999 may be the genetic biomarkers for prediction of colon cancer risk in Chinese population, the rs2585428 and rs6022999 may link to cancer susceptibility in Caucasian population and in Asian population respectly.

The POLR2E rs3787016 polymorphism is strongly associated with the risk of female breast and cervical cancer.

The rs3787016 polymorphism, in polymerase II polypeptide E (POLR2E), was previously identified as being associated with the risk for prostate cancer, esophageal cancer, breast cancer, papillary thyroid carcinoma and liver cancer, suggesting that rs3787016 may server as a common genetic factor to affect individual susceptibility to cancer. To prove the hypothesis, we here performed a case-control study to explore the association between rs3787016 and cervical cancer risk, and to confirm the association between rs3787016 and breast cancer in a central Chinese population, which was followed by a meta-analysis to precisely estimate the association between rs3787016 and risk of female breast and cervical cancer. The genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and confirmed by sequencing. Our results indicated that rs3787016 was associated with the risk of both breast cancer and cervical cancer, and stratified analysis indicated that the association remained particularly for ≤60 years old females who smoke and drink. Moreover, after grouping breast cancer and cervical cancer together, our meta-analysis demonstrated that rs3787016 was associated with overall cancer risk and breast cancer risk. Collectively, the POLR2E rs3787016 polymorphism may be a valuable biomarker for female breast and cervical cancer predisposition.

A comprehensive study of CD44 rs 187115 variant and cancer risk in a central Chinese population.

The rs187115, an intronic variant of CD44 gene, has been previously reported to play a potential role in genetic susceptibility to cancer. Here, we comprehensively examined the association between CD44 rs187115 variant and cancer risk (breast cancer, cervical cancer, lung cancer, gastric cancer, liver cancer, colon cancer, and rectal cancer) in a central Chinese population. The rs187115 variant was genotyped with the polymerase chain reaction-restriction fragment length polymorphism assay. In this study, we observed that rs187115 was associated with the risk of cervical, lung, and liver cancer, but not with the risk of breast, gastric, colon, rectal or colorectal cancer. Of note, the G allele and G allele genotypes of rs187115 conferred an increased risk of cervical, lung, and liver cancer. To improve the statistical strength, a followed meta-analysis was conducted. The results demonstrated that rs187115 was significantly associated with cancer risk, and the significant association remained in the stratification analysis by ethnicity, genotyping method, and cancer type. Collectively, the CD44 rs187115 variant may be associated with the risk of cervical, lung, and liver cancer in the central Chinese population, and may be used as a potential biomarker for cancer predisposition in the Asian population, especially in the Chinese population.

The association of POLR2E rs3787016 polymorphism and cancer risk: a Chinese case-control study and meta-analysis.

How single nucleotide polymorphisms in long non-coding RNAs are involved in cancer susceptibility remains poorly understood. We hypothesized that polymerase II polypeptide E (POLR2E) rs3787016 polymorphism, identified in a genome-wide association study of prostate cancer, might be a common genetic risk factor for cancer risk. To address this issue, we here conducted a case-control study to investigate the association of POLR2E rs3787016 polymorphism with risk of liver and lung cancer (including 800 normal controls, 480 liver cancer patients, and 550 lung cancer patients), followed by a meta-analysis. The genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism and confirmed by sequencing. Although no significant association was found for rs3787016 with risk of liver or lung cancer, the further stratified analysis identified that rs3787016 contributed to liver cancer risk particularly for over than 60 years individuals who drink. Moreover, the meta-analysis demonstrated that rs3787016 was associated with overall cancer risk and prostate cancer risk. Collectively, the POLR2E rs3787016 polymorphism may be a valuable biomarker for cancer predisposition.

The Study of MDM2 rs937283 Variant and Cancer Susceptibility in a Central Chinese Population.

The rs937283 variant, locating in murine double minute 2 promoter region, has been previously reported to potentially alter the promoter activity and to influence cancer susceptibility. In this study, we investigated the association of murine double minute 2 rs937283 variant and cancer susceptibility in a central Chinese population, followed by a meta-analysis. A total of 1058 healthy controls, 480 patients with breast cancer, 384 patients with cervical cancer, 480 patients with liver cancer, 426 patients with colon cancer, and 361 patients with rectal cancer were recruited in this case-control study. The murine double minute 2 rs937283 was genotyped by polymerase chain reaction restriction fragment length polymorphism and confirmed by sequencing. Our case-control analysis revealed that rs937283 was associated with the susceptibility to breast and liver cancer, but not cervical, colon, or rectal cancer. Specifically, the G allele of rs937283 conferred a significantly increased risk of breast and liver cancer. Moreover, results of meta-analysis demonstrated that rs937283 was significantly associated with cancer susceptibility, and this significant association remained in Asian (Chinese) population, but not in Caucasian population. Collectively, the murine double minute 2 rs937283 variant may serve as a potential biomarker for cancer predisposition in Chinese population.

A regulatory circuitry comprising TP53, miR-29 family, and SETDB1 in non-small cell lung cancer.

Lung cancer is a malignant tumor with high fatality rate and causes great harm to human economic life. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. With the rapid development of epigenetic study in the last decade, the understanding of the pathogenesis of lung cancer and the development of personalized treatment of lung cancer are picking up pace. Previous studies showed that miR-29 family members (miR-29s; miR-29a, -29b, and -29c) are down-regulated in most human cancers, including NSCLC, but their biological roles in tumorigenesis and their regulation mechanism are still not fully elucidated. Herein, we reported that the miR-29a, -29b and, -29c were coincidently down-regulated in NSCLC, and the histone H3K9 methyltransferase SET domain, bifurcated 1 (SETDB1) was directly targetted by miR-29s Moreover, SETDB1 negatively regulated the expression of TP53 and overexpression of SETDB1 down-regulating the expression of miR-29s, while TP53 positively regulated the expression of miR-29s and overexpression of TP53 down-regulated the expression of SETDB1. On the other side, as a downstream target of TP53, the H3K9 methyltransferase Suv39h1 was also down-regulated by miR-29s via up-regulating TP53 expression. The further detection of H3K9 methylation status after changes in miR-29s expression revealed that they negatively regulated the levels of H3K9 di- and trimethylation in NSCLC. Collectively, our findings highlight a TP53/miR-29s/SETDB1 regulatory circuitry and assign a role of H3K9 methylation regulator to miR-29s, which may be a potential therapeutic target in the treatment of NSCLC.

The MDM2 rs937283 A > G variant significantly increases the risk of lung and gastric cancer in Chinese population.

BACKGROUND: Currently, the MDM2 promoter rs937283 A > G variant that is able to alter MDM2 gene expression has been widely studied to explore the association of MDM2 with cancer risk. In this report, we investigate the association of MDM2 rs937283 A > G variant with risk of lung cancer (LC) and gastric cancer (GC) in a Chinese population of Hubei province, which was followed by a meta-analysis. METHODS: The genotyping of rs937283 was performed by polymerase chain reaction-restriction fragment length polymorphism and confirmed by sequencing. RESULTS: The results of the present study showed that rs937283 was significantly associated with the risk of LC, and the factors of age, gender, smoking status and drinking status would affect such association. However, rs937283 was only associated with the risk of GC in male, smoking and drinking subgroups. The following meta-analysis demonstrated that rs937283 was associated with the overall cancer risk particularly in Chinese population, which reinforced our present finding. Moreover, the meta-analysis according to cancer types revealed that rs937283 was associated with retinoblastoma risk, but not squamous cell carcinoma risk. CONCLUSION: Collectively, the MDM2 rs937283 A > G variant may be a valuable risk factor or diagnostic biomarker for Chinese cancer patients.

Long non-coding RNA POLR2E rs3787016 is associated with the risk of papillary thyroid carcinoma in Chinese population.

Long non-coding RNAs (LncRNAs) have been shown to be involved in cancer tumorigenesis and progression. Single nucleotide polymorphisms (SNPs) in the lncRNAs also play a vital role in carcinogenesis. We here explored the association between POLR2E rs3787016 and risk of papillary thyroid carcinoma (PTC) in a Chinese population, which was followed by a meta-analysis of POLR2E rs3787016 and cancer risk in Chinese population. A total of 409 PTC patients and 800 healthy individuals were enrolled in the present study. The POLR2E rs3787016 was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and was confirmed by sequencing. The POLR2E rs3787016T allele increased the PTC risk in Chinese population, particular in Chinese females. The meta-analysis further revealed that POLR2E rs3787016T allele was associated with an increased cancer risk in Chinese population. Collectively, the POLR2E rs3787016 may be used as a genetic biomarker to predict cancer risk in Chinese population.

Association of DNMT3B -283T>C polymorphism with risk of lung and gastric cancer: a case-control study and a meta-analysis.

PURPOSE: To investigate the association of DNMT3B -283T>C polymorphism with the risk of lung or gastric cancer, which was followed by a meta-analysis. METHODS: The genotyping of -283T>C was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and was confirmed by sequencing. RESULTS: The results of this case-control study showed that -283T>C was not associated with the risk of lung or gastric cancer, and further stratified analysis according to age, gender, smoking status, and alcohol status confirmed the present finding. However, data from a meta-analysis in the Asian population revealed a significant association between -283T>C and lung cancer risk in the allelic model (C vs. T: odds ratio [OR] = 1.28, 95% confidence interval [CI], 1.06-1.55, p = 0.01) and two genetic models (CC vs. TC: OR = 1.29, 95% CI, 1.04-1.59, p = 0.02; CC vs. TC + TT: OR = 1.30, 95% CI, 1.06-1.60, p = 0.01). CONCLUSIONS: These results provided evidence that the DNMT3B -283T>C polymorphism might significantly contribute to the lung cancer risk in the Asian population, but not the gastric cancer risk in the Chinese population.

The rs1550117 A>G variant in DNMT3A gene promoter significantly increases non-small cell lung cancer susceptibility in a Han Chinese population.

In this study, we conducted a case-control study to explore the association between rs1550117 A>G variant of DNMT3A gene promoter and non-small cell lung cancer (NSCLC) susceptibility in a Han Chinese population. The genotyping of rs1550117 A>G variant was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and confirmed by sequencing. Allele G of rs1550117 was associated with an increased risk of NSCLC. Moreover, individuals carrying the GG genotypes had a higher risk to develop NSCLC than the AA and GA genotype carriers. Further stratified analysis showed that rs1550117 A>G was significantly related to age (> 60 years), male, smoking and drinking. In vivo detection of DNMT3A mRNA levels in NSCLC tissues and in vitro luciferase assays consistently showed that the allele G significantly decreased DNMT3A transcription. Additional functional analysis revealed that the increased binding affinity of transcription repressor SP1, which was associated with allele G of rs1550117, led to the significant decreased expression of DNMT3A. Collectively, our results propose a suppression role of DNMT3A in NSCLC development and emphasize the dual roles of DNMT3A in tumorigenesis.

The DNMT3B -579G>T Polymorphism Is Significantly Associated With the Risk of Gastric Cancer but not Lung Cancer in Chinese Population.

The -149C>T and -579G>T, 2 single nucleotide polymorphisms in de novo methyltransferase 3B gene promoter, have been previously reported to potentially alter the promoter activity and to influence cancer risk. However, the results from previous studies remain conflicting rather than conclusive. In view of this, we conducted a case-control study and then a meta-analysis to examine the association between these 2 single-nucleotide polymorphisms with risk of lung and gastric cancer in Chinese population. The genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism and confirmed by sequencing. In this case-control study, no significant association with lung or gastric cancer risk was observed for -149C>T, while -579G>T was significantly correlated with the risk of gastric cancer but not lung cancer. Moreover, haplotype analysis showed that haplotype -149T/-579 T, which carried the risk -579 T allele, significantly increased the susceptibility to gastric cancer. However, none of the haplotypes was associated with the risk of lung cancer. The following meta-analysis involved only Chinese population and further confirmed the significant association of -579G>T with gastric cancer but not lung cancer and suggested no significant association between -149C>T and risk of lung or gastric cancer. Collectively, DNMT3B -579G>T polymorphism is associated with gastric cancer risk in Chinese population, and the -579G>T may be used as a genetic biomarker to predict the risk of gastric cancer in Chinese population.