lncRNA Single-nucleotide Polymorphisms Research Articles

Genetic risk and gastric cancer: polygenic risk scores in population-based case-control study

ABSTRACT Objective This study aimed to screen and identify common variants and long noncoding RNA (lncRNA) single nucleotide polymorphisms (SNPs) associated with gastric cancer risk, and construct prediction models based on polygenic risk score (PRS). Methods The risk factors associated with gastric cancer were screened following meta-analysis and bioinformatics, verified by population-based case-control study. We constructed PRS and weighted genetic risk scores (wGRS) derived from the validation data set. Net reclassification improvement (NRI), integrated discrimination improvement (IDI), Akaike information criterion (AIC) and Bayesian information criterion (BIC) were used to evaluate model. Results The PRS was divided into 10 quantiles, with the 40–60% quantile as a reference. A risk gradient was revealed across quantile of the PRS, the risk of gastric cancer in the highest 10 quantile of PRS was 3.24-fold higher than that in control population (OR = 3.24, 95%CI: 2.07, 5.06). For NRI and IDI, PRS combinations were significantly improved compared to wGRS model combinations (P < 0.001). The model of PRS combined with lncRNA SNPs, smoking, drinking and Helicobacter pylori infection was the best-fitting model (AIC = 117.23, BIC = 122.31). Conclusion The model based on PRS combined with lncRNA SNPs, H. pylori infection, smoking, and drinking had the optimal predictive ability for gastric cancer risk, which was helpful to distinguish high-risk groups.

Emerging long noncoding RNA polymorphisms as novel predictors of survival in cancer.

Long non coding RNAs (lncRNAs) are involved in the tumor growth, invasion, metastasis, and cancer recurrence. The improper expression of certain lncRNAs is correlated with the prognosis of the cancer patients. LncRNA single nucleotide polymorphisms (SNPs) largely affect the expression, structure, and function of lncRNAs. Therefore, they affect cancer prognosis and susceptibility. In the present review, we tried to collect all published papers on the prognostic ability in cancer considering the correlation of different lncRNAs polymorphism and survival. We explored the association between lncRNA (i.e. MALAT1, ANRIL, GAS5, TP73-AS1, HOTAIR, H19, LncARSR, PVT1, HOTTIP, PRNCR1, PCAT1, CASC8, UCA1, SNHG5, PARP1, Linc00312, and NEAT) polymorphisms with cancer prognosis. The HOTAIR rs920778/rs4759314 and MALAT1 rs664589 polymorphisms play an important role in cancer relevant functions. Other lncRNAs polymorphisms are special for certain kinds of cancer, indicating their function in specific signaling pathways. Accordingly, the individual or combined genotypes of lncRNA polymorphisms are able to predict cancer prognosis. However, most of the samples are Chinese and do not represent the global population. More large-scale trials of different ethnic groups as well as comprehensive health records are therefore needed for more validation of the results.

Genetic variants in long non-coding RNAs UCA1 and NEAT1 were associated with the prognosis of oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) is known for its high incidence, death rate, and relatively low 5-year survival. Long non-coding RNAs (lncRNAs) have been shown to play a significant role in cancerization and cancer progression. However, research on the association of polymorphisms in these lncRNAs with the prognosis of OSCC is lacking. Fifteen functional single-nucleotide polymorphisms (SNPs) in seven lncRNAs were selected to explore the relationship between these lncRNA SNPs and the prognosis among 209 OSCC patients. Kaplan–Meier analysis and Cox proportional hazards regression models were used to examine the associations. Further functional exploration of significant SNPs was done by eQTL analysis. Using multivariate Cox hazards regression analysis, a predictive role of NEAT1 rs3741384 GG and UCA1 rs7255437 TC+TT in a worse prognosis of OSCC was identified. In addition, a marked increased risk of death was observed with an increasing number of unfavourable genotypes (NUG). The NUG was then incorporated with clinical variables in the receiver operating characteristic curve, and the results indicated a potential role of the NUG in predicting OSCC patient risk of death (area under the curve increase from 0.616 to 0.703). In conclusion, the study findings indicate that genetic variants rs3741384 in NEAT and rs7255437 in UCA1 may influence the survival of OSCC patients.

Association of Long Non-Coding RNA Polymorphisms with Gastric Cancer and Atrophic Gastritis.

Long non-coding RNAs (lncRNA) play an important role in the carcinogenesis of various tumours, including gastric cancer. This study aimed to assess the associations of lncRNA ANRIL, H19, MALAT1, MEG3, HOTAIR single-nucleotide polymorphisms (SNPs) with gastric cancer and atrophic gastritis. SNPs were analyzed in 613 gastric cancer patients, 118 patients with atrophic gastritis and 476 controls from three tertiary centers in Germany, Lithuania and Latvia. Genomic DNA was extracted from peripheral blood leukocytes. SNPs were genotyped by the real-time polymerase chain reaction. Results showed that carriers of MALAT1 rs3200401 CT genotype had the significantly higher odds of atrophic gastritis than those with CC genotype (OR-1.81; 95% CI 1.17–2.80, p = 0.0066). Higher odds of AG were found in a recessive model (CC vs. TT + CT) for ANRIL rs1333045 (OR-1.88; 95% CI 1.19–2.95, p = 0.0066). Carriers of ANRIL (rs17694493) GG genotype had higher odds of gastric cancer (OR-4.93; 95% CI 1.28–19.00) and atrophic gastritis (OR-5.11; 95% CI 1.10–23.80) compared with the CC genotype, and carriers of HOTAIR rs17840857 TG genotype had higher odds of atrophic gastritis (OR-1.61 95% CI 1.04–2.50) compared with the TT genotype; however, the ORs did not reach the adjusted significance threshold (p < 0.007). In summary, our data provide novel evidence for a possible link between lncRNA SNPs and premalignant condition of gastric cancer, suggesting the involvement of lncRNAs in gastric cancer development.

Association between long non-coding RNA polymorphisms and cancer risk: a meta-analysis.

Several studies have suggested that long non-coding RNA (lncRNA) gene polymorphisms are associated with cancer risk. In the present study, we conducted a meta-analysis related to studies on the association between lncRNA single-nucleotide polymorphisms (SNPs) and the overall risk of cancer. A total of 12 SNPs in five common lncRNA genes were finally included in the meta-analysis. In the lncRNA antisense non-coding RNA (ncRNA) in the INK4 locus (ANRIL), the rs1333048 A/C, rs4977574 A/G, and rs10757278 A/G polymorphisms, but not rs1333045 C/T, were correlated with overall cancer risk. Our study also demonstrated that other SNPs were correlated with overall cancer risk, namely, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1, rs619586 A/G), HOXA distal transcript antisense RNA (HOTTIP, rs1859168 A/C), and highly up-regulated in liver cancer (HULC, rs7763881 A/C). Moreover, four prostate cancer-associated ncRNA 1 (PRNCR1, rs16901946 G/A, rs13252298 G/A, rs1016343 T/C, and rs1456315 G/A) SNPs were in association with cancer risk. No association was found between the PRNCR1 (rs7007694 C/T) SNP and the risk of cancer. In conclusion, our results suggest that several studied lncRNA SNPs are associated with overall cancer risk. Therefore, they might be potential predictive biomarkers for the risk of cancer. More studies based on larger sample sizes and more lncRNA SNPs are warranted to confirm these findings.

Long non-coding RNA polymorphisms in 6p21.1 are associated with atrophic gastritis risk and gastric cancer prognosis.

It has been suggested that the genetic variation in human chromosome 6p21.1 has potential importance for the susceptibility to gastric cancer (GC). The study aims to explore the relationship between the long non-coding RNA (lncRNA) polymorphisms in 6p21.1 and the risk of GC as well as atrophic gastritis (AG). Genotyping for eight single nucleotide polymorphisms (SNPs) was conducted using Sequenom MassARRAY platform in a total of 2507 northern Chinese subjects, including 749 GC cases, 878 AG cases and 880 controls. The results showed rs61516247 was associated with an increased AG risk in overall population (AA vs. GG: P = 0.046, OR = 1.46; A vs. G: P = 0.037, OR = 1.18). Four SNPs, rs61516247, rs1886753, rs7747696 and rs7749023 were associated with AG risk in some specific subgroups. Among them, rs1886753 had an interaction effect with H.pylori infection on AG risk (Pinteraction = 0.038, OR = 1.62). In prognosis analysis, two SNPs, rs80112640 (AG+GG vs. AA: P = 0.047, HR = 0.56; G vs. A: P = 0.039, HR = 0.57) and rs72855279 (P = 0.043, HR = 0.57) were found to improve the overall survival of GC patients. In conclusion, lncRNA SNPs in 6p21.1 are associated with AG risk and GC prognosis. Our study provides all-new research clues for screening lncRNA-based biomarkers in the cancer-related hotspot region 6p21.1 with the potential to predict risk and prognosis of GC along with its precursor.

A systematic review and meta-analysis of the association between long non-coding RNA polymorphisms and cancer risk.

It has been suggested that long non-coding RNA (lncRNA) gene polymorphisms are associated with cancer risk. In this article, we conducted a systematic review related to studies on the association between lncRNA single-nucleotide polymorphisms (SNPs) and the overall risk of cancer. A total 17 SNPs in four common lncRNA genes were included in the meta-analysis. In the lncRNA H19, the rs2735971 A/G, rs2839698C/T, and rs3024270 G/C polymorphisms, but not rs217727C/T, were correlated with overall cancer risk. The results also suggested that other SNPs were correlated with overall cancer risk, namely, two in HOTAIR (HOX transcript antisense RNA: rs920778C/T and rs7958904 G/C) and two in PRNCR1 (rs1016343C/T and rs16901946 A/G). No association was found between the three ZNRD1-AS1 (ZNRD1 antisense RNA 1) SNPs and the risk of cancer. In summary, our findings suggest that quite a few studied lncRNA SNPs are associated with overall cancer risk; therefore, they are potential predictive biomarkers for the risk of cancer. Moreover, other lncRNA SNPs investigated were also relevant to cancer but studies on them are limited, and they were also briefly reviewed as candidate cancer markers.