• LEPR
• non‐small cell lung cancer
• obesity
• overweight
• polymorphism

• Humans
• Receptors, Leptin/genetics
• Carcinoma, Non-Small-Cell Lung/genetics
• Carcinoma, Non-Small-Cell Lung/pathology
• Polymorphism, Single Nucleotide
• Male
• Female
• Lung Neoplasms/genetics
• Middle Aged
• Genetic Predisposition to Disease
• Case-Control Studies
• Genotype
• Aged
• Alleles
• Genetic Association Studies

• RC2021-009 Initial Research Project for Talents of Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School
• M202153 Scientific Research Project of Wuxi Health Commission

Recently, many investigations have suggested that the rs3746444 T>C locus in the microRNA (miR)-499 gene may contribute to the occurrence of cancer. However, reports on the association between rs3746444 and hepatocellular carcinoma (HCC) are conflicting.

To further understand and explore the potential correlation between the single-nucleotide polymorphism of rs3746444 and the incidence of HCC.

In this meta-analysis, we obtained electronic literature by searching the PubMed, Embase and Chinese BioMedical Disc databases (through May 20, 2022). All eligible case-control, prospective cohort or nested case-control studies with sufficient data for calculating the odds ratios with their 95% confidence intervals were included.

Ultimately, a total of 17 independent studies were included. We identified that rs3746444 was associated with the development of HCC (C vs T: P = 0.019 and CC/CT vs TT: P = 0.016). In Asian individuals, rs3746444 was associated with susceptibility to HCC (C vs T: P = 0.013 and CC/CT vs TT: P = 0.016). In addition, this study identified that the miR-499 rs3746444 locus was associated with susceptibility to HCC in the normal/healthy control subgroup (C vs T: P = 0.034 and CC/CT vs TT: P = 0.024).

In summary, this meta-analysis highlights that rs3746444 in the miR-499 gene is involved in the occurrence of HCC, especially in Asian individuals.

• Polymorphism
• MicroRNA-499
• Hepatocellular carcinoma
• Meta-analysis
• Susceptibility

MicroRNAs (miRNAs) are a group of small, non‐coding, and endogenous RNAs that regulate gene expression and over 50% of them are located at cancer‐related genomic regions or fragile sites. According to previous studies there is significant association of miRNA single nucleotide polymorphisms (SNPs) with tumorigenesis (e.g., esophageal cancer, hepatocellular cancer, gastric cancer, bladder cancer, breast cancer, lung cancer, and colon cancer), however, the conclusions have been inconsistent. To investigate the relationship between miR‐146a rs2910164 C > G, miR‐196a2 rs11614913 T > C, and miR‐499 rs3746444 A > G polymorphisms and the susceptibility to esophageal squamous cell cancer (ESCC) in the Chinese Han nationality, we recruited 829 cases and 1522 controls in our study. In this case–control study, our results suggest that the rs3746444 GG genotype increased ESCC risk [homozygote model: adjusted odds ratio (OR), 2.26; 95% CI, 1.33–3.83; p = 0.003, recessive model: adjusted OR, 2.34; 95% CI, 1.38–3.96; p = 0.002], which remained consistent after Bonferroni correction. There was no association of rs11614913 and rs2910164 polymorphisms with ESCC. After adjusting by age, sex, smoking, and drinking status and body mass index (BMI), the multiple logistic analysis suggested that rs11614913 T → C variation reduced ESCC susceptibility in females and in the ≥63 years old subgroups, while rs2910164 C → G variation increased ESCC risk in both two BMI subgroups.

• ESCC
• microRNA
• polymorphism
• susceptibility

Long non-coding RNAs (LncRNAs) play vital roles in the tumorigenesis of many cancers. Single nucleotide polymorphisms (SNPs) of the lncRNA also play vital roles in tumorigenesis. We explored lncRNA rs944289 and rs7990916 polymorphisms and analyzed the relationship between these lncRNA polymorphisms with the colorectal cancer (CRC) risk in a Chinese population. We recruited 1003 CRC patients from the Affiliated People’s Hospital of Jiangsu University and the Fujian Medical University Union Hospital from October 2014 to August 2017. Genomic DNA was extracted using a DNA Kit from lymphocytes of peripheral blood and the genotyping was performed with a SNPscan method. We found that the rs944289 TT homozygote was associated with the decreased CRC risk in the overall population. LncRNA rs944289 TT decreased the CRC risk in the subgroup of female, male, age ≥ 61, without alcohol intake, smoking and BMI ≥ 24 by logistic regression. The subgroup analysis revealed that lncRNA rs7990916 was not associated with CRC risk except for age < 61. Logistic regression analysis revealed that lncRNA rs944289 TT homozygote was associated with the increased risk of rectum cancer (TT vs. CC + CT: adjusted OR = 1.29, 95% CI 1.10–1.66, P = 0.041) or colon cancer. In summary, we proved that lncRNA rs944289 might be significantly related to the decreased CRC risk in the Chinese Han populations and lncRNA rs7990916 was not associated with the CRC risk except for patients of age < 61. In the future, studies with larger samples should be conducted to validate our results.

Leishmania are intracellular protozoan parasites that cause a wide spectrum of clinical manifestations in genetically susceptible individuals with an insufficient or balanced Th1 immune response to eliminate the parasite. MiRNAs play important regulatory role in numerous biological processes including essential cellular functions. miR146-a acts as an inhibitor of interleukin 1 receptor associated kinase 1 (IRAK1) and tumour necrosis factor (TNF) receptor associated factor 6 (TRAF6) present in the toll-like receptors pathway while miR499a modulates TGF-β and TNF signalling pathways. Here, we investigated whether MIRNA146A rs2910164 and MIRNA499 rs3746444 variants are associated with the development of L. guyanensis (Lg)-cutaneous leishmaniasis (CL). The variants MIR146A rs2910164 and MIR499A rs3746444 were assessed in 850 patients with Lg-CL and 891 healthy controls by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Plasma cytokines were measured using the BioPlex assay. Carriers of rs2910164 CC genotype have 30% higher odds of developing CL (ORadj_age/sex = 1.3 [95%CI 0.9–1.8]; Padj_age/sex 0.14) compared to individuals with the genotype GG (ORadj_age/sex = 0.77 [95%CI 0.56–1.0]; Padj_age/sex 0.14) if exposed to Lg-infection. Heterozygous GC individuals also showed lower odds of developing CL (ORadj_age/sex = 0.77 [95%CI 0.5–1.1]; Padj_age/sex 0.09). Homozygosity for the allele C is suggestive of an association with the development of Lg-CL among exposed individuals to Lg-infection. However, the odds of developing CL associated with the CC genotype was evident only in male individuals (OR_adjage = 1.3 [95% CI = 0.9–2.0]; P_adjage = 0.06). Individuals homozygous for the G allele tend to have higher plasma IL-8 and CCL5. Similarly, for the MIR499A rs3746444, an association with the G allele was only observed among male individuals (OR = 1.4 [1.0–1.9]; P = 0.009). In a dominant model, individuals with the G allele (GG-GA) when compared to the AA genotype reveals that carriers of the G allele have 40% elevated odds of developing Lg-CL (ORadj_age = 1.4 [1.1–1.9]). Individuals with the GG genotype have higher odds of developing Lg-CL (ORadj_age/sex = 2.0 [95%CI 0.83–5.0]; P_adjage = 0.01. Individuals homozygous for the G allele have higher plasma IL-8. Genetic combinations of both variants revealed that male individuals exposed to Lg bearing three or four susceptible alleles have higher odds of developing Lg-CL (OR = 2.3 [95% CI 1.0–4.7]; p = 0.017). Both MIR146A rs2910164 and MIR499A rs3746444 are associated with the development of Lg-CL and this association is prevalent in male individuals.

Leishmaniasis is caused by infection with Leishmania parasites. In regions with the presence of Leishmania parasites, all people do not develop the disease despite similar exposure. Only a proportion of inhabitants progress to the development of disease. Clinical manifestations depend on the vector and Leishmania species, as well the host genetic background and genetically determined immune responses. miRNAs play important roles in regulating gene expression and many biological processes including immune pathways. miR-146a targets TRAF6 and IRAK1 genes, that encode key adaptor molecules downstream of toll-like receptors (TLRs). TLRs are critical in immune response to Leishmania-infection. miR499-a modulates inflammation-related signalling pathways such as TGFβ, TNFα and TLR pathways. In this study, we showed that MIR146A and MIR499A variants are risk factors to developing cutaneous leishmaniasis caused by L. guyanensis in Amazonas state of Brazil. Individuals with these variants are susceptible to the development of CL.

• Adult
• Alleles
• Cytokines/blood
• Female
• Genetic Predisposition to Disease
• Genotype
• Humans
• Interleukin-1 Receptor-Associated Kinases
• Interleukin-8/blood
• Interleukin-8/metabolism
• Intracellular Signaling Peptides and Proteins
• Leishmania guyanensis
• Leishmaniasis, Cutaneous/genetics
• Male
• MicroRNAs/genetics
• Middle Aged
• Polymorphism, Restriction Fragment Length
• Polymorphism, Single Nucleotide

• Conselho Nacional de Desenvolvimento Científico e Tecnológico
• Fundação de Amparo à Pesquisa do Estado do Amazonas

• Esophageal squamous cell carcinoma
• Interleukin-4
• Interleukin-4 receptor
• Polymorphism
• Risk

C677T (Ala>Val, rs1801133 C>T), a non-synonymous variant of methylenetetrahydrofolate reductase (MTHFR) gene, has been found to be associated with an impair enzyme activity of MTHFR. The relationship of MTHFR rs1801133 with hepatocellular carcinoma (HCC) has been extensively investigated. However, the findings were conflicting. Recently, more investigations have been conducted on the relationship of MTHFR rs1801133 with HCC. To obtain a more precise assessment on the effect of this non-synonymous variant to the development of HCC, a pooled-analysis was performed. This meta-analysis consisted of 19 independent case–control studies. By using the odds ratio (OR) combined with 95% confidence interval (CI), the relationship of MTHFR rs1801133 with HCC risk was determined. A total of 19 independent case–control studies were included. Finally, 6,102 HCC cases and 6,526 controls were recruited to examine the relationship of MTHFR rs1801133 with HCC risk. In recessive model (TT vs. CC/CT), the findings reached statistical significance (OR, 0.90; 95%CI, 0.82–0.98; P = 0.016). Subgroup analysis also found an association between MTHFR rs1801133 polymorphism and the decreased risk of HCC in hepatitis/virus related patients (recessive model: OR, 0.85; 95%CI, 0.72–0.99; P = 0.035, and allele model: OR, 0.90; 95%CI, 0.81–0.99; P = 0.028). Subgroup analyses indicated that extreme heterogeneity existed in Asian population, larger sample size investigation, hospital-based study and normal/healthy control subgroups. The shape of Begger’s seemed symmetrical. Egger’s linear regression test also confirmed these evaluations. Sensitivity analyses suggested that our findings were stable. In summary, our results highlight that MTHFR rs1801133 polymorphism decreases HCC susceptibility. The relationship warrants a further assessment.

• Hepatocellular carcinoma
• MTHFR
• Meta-analysis
• Polymorphism
• Susceptibility

MicroRNA (miR) acts as a negative regulator of gene expression. Many literatures have suggested that miRs may be involved in the process of cell proliferation, inflammation, oxidative stress, energy metabolism and epithelial–mesenchymal transition. Thus, miRs may be implicated in the occurrence of non-small cell lung cancer (NSCLC). In the current investigation, we included 2249 subjects (1193 NSCLC patients and 1056 controls) and designed a study to identify the relationship of miR-146a rs2910164 C/G, -499a rs3746444 A/G and -196a-2 rs11614913 T/C with the risk of NSCLC. The risk factors (e.g., body mass index (BMI), sex, smoking, drinking and age) was used to adjust the odds ratios (ORs) and 95% confidence intervals (CIs). After conducting a power value assessment, we did not confirm that the miR-single nucleotide polymorphisms (SNPs) genotypic distributions were different in NSCLC cases and controls. However, the association of miR-196a-2 rs11614913 with a decreased risk of NSCLC was identified in the female subgroup (adjusted P=0.005, power = 0.809 for TC vs. TT, and adjusted P=0.004, power = 0.849 for CC/TC vs. TT). In addition, gene–gene interaction analysis showed that rs11614913 TC/3746444 AA and rs11614913 CC/rs3746444 AA could also reduce the susceptibility to NSCLC (rs11614913 TC/rs3746444 AA vs. rs11614913 TT/rs3746444 AA, P=0.001, power = 0.912 and rs11614913 CC/rs3746444 AA vs. rs11614913 TT/rs3746444 AA, P=0.003, power = 0.836). In conclusion, in overall comparisons, we did not confirm that the rs2910164, rs3746444, and rs11614913 SNPs genotypic distributions were different in NSCLC cases and controls. However, this case–control study demonstrates that miR-196a-2 rs11614913 may be a protective factor for the development of NSCLC among female patients.

• microRNA
• non-small cell lung cancer
• polymorphism
• susceptibility

• MicroRNA-499
• gastric cancer
• polymorphism

• ICAM-1
• colorectal cancer
• polymorphism
• risk

Background: Variants in B- and T-lymphocyte attenuator (BTLA) gene are likely to affect the function of BTLA protein.

Methods: In the present case–control study, we selected BTLA tagging single-nucleotide polymorphisms (SNPs) (rs16859629 T>C, rs1982809 G>A, rs2171513 G>A and rs3112270 A>G) and conducted a case–control study to identify the association of BTLA SNPs with risk of esophagogastric junction adenocarcinoma (EGJA). The present study involved 1236 new incident EGJA cases and 1540 cancer-free controls.

Results: The genotypes of BTLA SNPs were analyzed using a SNPscan Kit. No association was also found between the BTLA SNPs and the susceptibility of EGJA in overall comparsion. In subgroup analyses, the BTLA rs1982809 was found to be associated with an increased susceptibility of EGJA (AA versus GG: OR^adjusted = 2.09, 95% CI 1.08–4.07, P = 0.030; and AA versus GA/GG: OR^adjusted = 1.99, 95% CI 1.04–3.82, P = 0.039). In haplotype comparison, we identified that TAAG haplotype with the order of BTLA rs16859629, rs1982809, rs2171513 and rs3112270 SNPs might increase the susceptibility of EGJA (OR = 3.07, 95% CI = 1.41–6.71; P = 0.003).

Conclusion: To conclude, the present study suggests that BTLA T_rs16859629A_rs1982809A_rs2171513G_rs3112270 haplotype may increase the susceptibility of EGJA. More studies should be conducted to evaluate whether BTLA polymorphisms may influence the susceptibility of cancer in the future.

• BTLA
• Immune
• Lymphocyte
• Polymorphism
• adenocarcinoma

• esophagogastric junction adenocarcinoma
• lncRNA
• polymorphism
• susceptibility

• hepatocellular carcinoma
• miRNA-146a
• miRNA-196a2
• miRNA-499
• polymorphism

• coronary artery disease
• microRNA
• polymorphism
• risk