Skip to main content
NCBI home page
Asian Pacific Journal of Cancer Prevention : APJCP logoLink to Asian Pacific Journal of Cancer Prevention : APJCP
. 2020 May;21(5):1221–1226. doi: 10.31557/APJCP.2020.21.5.1221

Association of EGLN2 rs10680577 Polymorphism with the Risk and Clinicopathological Features of Patients with Prostate Cancer

Nahid Rahimi 1, Mahsa Azizi 1, Gholamreza Bahari 2,*, Behzad Narouie 3, Mohammad Hashemi 1,4
PMCID: PMC7541883  PMID: 32458625

Abstract

Several studies have evaluated the association between EGLN2 4-bp insertion/deletion (ins/del) polymorphism (rs10680577) and many cancers. However, up to date, no study has inspected the impact of rs10680577 polymorphism on prostate cancer (PCa) risk. This case-control study was achieved on 170 pathologically confirmed PCa patients and 196 cancer free men to inspect whether rs10680577 variant is related to the risk and clinicopathological features of patients with PCa. Genotyping was performed by mismatched polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The findings did not support an association between the variant with the risk and clinicopathological characteristics of PCa patients. When we pooled our results with six preceding studies, the findings suggested that rs10680577 variant significantly augmented the risk of overall cancer in heterozygous (OR=1.38, 95 % CI=1.26-1.52, p<0.00001, ins/del vs ins/ins), homozygous (OR=1.66, 95 % CI=1.05-2.61, p=0.029, del/del vs ins/ins), codominant (OR=1.44, 95%CI=1.32-1.58, p<0.00001, ins/del+del/del vs ins/ins), and allele (OR=1.32, 95%CI=1.18-1.49, p<0.00001, del vs ins) genetic models. Additional well designed studies with larger sample sizes are necessary to confirm our findings.

Key Words: EGLN2- RERT, lncRNA, prostate cancer, polymorphism, indel

Introduction

Prostate cancer (PCa) is one of the most common cancer among men globally (Jemal et al., 2011). The precise mechanisms underlying PCa development is largely unknown. Mounting evidence suggests that genomic and environmental factors play a role in development and progression of PCa (Cunningham et al., 2003; Chokkalingam et al., 2007; Zhou et al., 2015; Sattarifard et al., 2018). Small insertions/deletions (indels), the second most common form of genetic variations in human genome, have been linked to cancer development (Mullaney et al., 2010; Hashemi et al., 2018a; Hashemi et al., 2018c; Hashemi et al., 2018d).

EGLN2 (Egl nine homolog 2) gene which is located on chromosome 19 (19q13.2) encodes prolyl hydroxylases 1 (PHD1) (Ryan et al., 2014).

Hypoxia, a main characteristic of solid tumors, leads to alterations of gene expression in tumor cells to adapt to the hypoxic environment (Brahimi-Horn et al., 2007). The hypoxia-inducible factor 1 (HIF-1), a key transcriptional activator is induced by hypoxia (Semenza, 1999). The HIF-1 plays a critical role in the development of solid tumors and in coordinating the cellular response to hypoxia and oxygen homeostasis (Maxwell and Ratcliffe, 2002; Semenza, 2007; Kaelin and Ratcliffe, 2008). The level of HIF-1 is tightly regulated by three PHDs (PHD1, PHD2 and PHD3) (Appelhoff et al., 2004; Willam et al., 2004). In normoxia condition HIF is hydroxylated at specific residues by PHDs which uses oxygen as a substrate. Hydroxylated HIF binds to a protein called Von Hippel Lindau protein (VHL) for its degradation, while in hypoxic situation, stabilization and nuclear translocation occur, leading to oncogenes activation (Appelhoff et al., 2004; Stolze et al., 2006; Pezzuto and Carico, 2018).

Several studies investigated the correlation between EGLN2 4-bp ins/del polymorphism (rs10680577) and susceptibility to various cancer comprising breast cancer (Hashemi et al., 2018b), colorectal cancer (Li et al., 2017), gastric cancer (Wang et al., 2014), hepatocellular carcinoma (HCC) (Zhu et al., 2012), and lung cancer (Che et al., 2014; Zhu et al., 2018), As far as we know, there is no data concerning the impact of EGLN2 4-bp ins/del polymorphism on PCa susceptibility. Consequently, the current study aimed to assess the impact of this variant on PCa development.

Materials and Methods

This case-control study conducted on 170 histologically confirmed PCa patients and 196 cancer free men. The study design and enrollment procedure have been explained previously (Hashemi et al., 2017a; Hashemi et al., 2017b; Sattarifard et al., 2018). The study was approved by the Zahedan University of Medical Sciences ethics committee and all participants were asked to provide their written informed consent. Whole blood samples were collected in EDTA tube, and genomic DNA was purified by salting out method.

Genotyping

Genotyping of EGLN2 4-bp ins/del (rs10680577) polymorphism was done by mismatch polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) as described previously (Hashemi et al., 2018b). The forward and reverse primers were 5`-CCGTTATAAAAGATACTTATGTAAATCAC-3` and 5`-TTGGAATCAAGTGGCGTCG-3`, respectively. PCR was achieved using Prime Taq Premix (Genet Bio, Korea) and the PCR products were digested by AleI restriction enzyme. The del allele digested and created 224 and 31 bp fragments, whereas the ins allele remained undigested (259 bp).

Statistical analysis

All analyses were conducted with SPSS 22 statistical package. The χ2 and independent sample t-test were used for categorical and continuous data, respectively. Odds ratios (ORs) and 95% confidence intervals (95% CIs) was estimated by logistic regression analysis. P value < 0.05 was considered statistically significant.

Pooled analysis

Pooling of our outcomes with six previous published studies was done using STATA 14.1 software. Electronic databases were searched for all articles describing the relationship between EGLN2 4-bp ins/del polymorphism and cancer susceptibility. The characteristic of study included into pooled analysis is shown in Table 3. The relationship between EGLN2 polymorphism and cancer risk was assessed by pooled ORs and their 95% CIs. The significance of the pooled OR was assessed by the Z-test, and P<0.05 was considered to be statistically significant. Heterogeneity between studies was determined by I2 test and Q test. The I2≥50% or PQ< 0.1 showed the presence of heterogeneity. If heterogeneity exists the random effect model was applied. We determined publication bias using Begg’s funnel plot and Egger’s test. Sensitivity analyses were conducted in order to assess the data stability.

Table 3.

Characteristics of All Studies Included in the Meta-Analysis

Author Year Country Ethnicity Cancer type Source of control Genotyping Method Case/control Cases
 Controls
Ins/ins Ins/del del/del ins del Ins/ins Ins/del del/del ins del
Che 2014 China Asian NSLC HB PCR-PAGE 406/812 241 154 11 636 176 536 252 24 1324 300
Hashemi 2018 Iran Asian Breast cancer HB PCR-RFLP 134/154 35 94 5 164 104 50 91 13 191 117
Li 2017 China Asian CRC HB PCR-PAGE 1008/1240 571 383 54 1525 491 825 383 32 2033 447
Wang 2014 China Asian Gastric cancer HB PCR-PAGE 415/830 235 159 21 629 201 541 266 23 1348 312
Zhu 2018 China Asian Lung cancer HB PCR-PAGE 376/419 222 117 37 561 191 283 125 11 691 147
Zhu 2012 China Asian HCC HB PCR-PAGE 1067/1692 607 406 54 1620 514 1125 522 45 2772 612
Current study Iran Asian Prostate cancer HB PCR-RFLP 170/196 51 109 10 211 129 59 118 19 236 156
Open in a new tab

Results

The study group consisted of 170 histologically confirmed PCa (mean age: 61.2±6.6 years) and 196 cancer free men (mean age: 64.5±8.9 years). Statistically significant difference was observed between cases and controls groups regarding age (p<0.05). The frequency distribution of genotype and allele is shown in Table 1. The results indicated that EGLN2 4-bp ins/del polymorphism was not correlated with PCa susceptibility in heterozygous (OR=0.98, 95%CI=0.61-1.57, p=0.816), homozygous (OR=0.50, 95%CI=0.21-1.21, p=0.126) dominant (OR=0.91, 95%CI= 0.58-1.45, p=0.695, recessive (OR=1.95, 95%CI=0.87-4.41, p=107) and allele (OR=0.92, 95%CI=0.69-1.25, p=0.649) genetic models.

Table 1.

Genotype and Allele Frequencies of EGLN2 rs10680577 (4-bp ins/del) Polymorphism in PCa and Controls

4-bp ins/del polymorphism Case
n (%)		 Control
n (%		 *OR (95%CI) *P
Codominant
ins/ins 51 (30.0) 59 (30.1) 1 -
ins/del 109 (64.1) 118 (60.2) 0.98 (0.61-1.57) 0.816
del/del 10 (5.9) 19 (9.7) 0.50 (0.21-1.21) 0.126
Dominant
ins/ins 51 (30.0) 59 (30.1) 1 -
ins/del+del/del 119 (70.0) 137 (69.9) 0.91 (0.58-1.45) 0.695
Recessive
Ins/del+ins/ins 160 (94.1) 177 (90.3) 1 -
De/del 10 (5.9) 19 (9.7) 1.95 (0.87-4.41) 0.107
Allele
ins 211 (62.0) 236 (60.2) 1 -
del 129 (38.0) 156 (39.8) 0.92 (0.69-1.25) 0.649
Open in a new tab

*Adjusted by age

The relationship between the variant and clinicopathological features such as age, stage, prostate specific antigen (PSA) level, Gleason score, perineural invasion, and surgical margin were determined (Table 2). The results indicated no significant relationship between the variant and clinicopathological features.

Table 2.

Association between EGLN2 4-bp ins/del Polymorphism and Clinical Characteristics of Prostate Cancer Patients

Characteristic of patients EGLN2 4-bp ins/del
 p
Ins/ins Ins/del Del/del
Age at diagnosis (years, n) 0.32
≤60 22 54 7
>60 28 55 3
Stage 0.554
pT1 2 5 1
pT2a 3 20 2
pT2b 2 8 1
pT2c 30 50 5
pT3a 3 6 1
pT3b 10 20 0
PSA level at diagnosis (ng/ml), n 0.923
≤4 1 1 0
4-10 26 54 6
>10 23 54 4
Gleason score, n 0.228
≤7 40 84 10
>7 10 25 0
Perineural invasion, n 0.567
Positive 31 72 5
Negative 19 37 5
Surgical margin, n 0.883
Positive 17 40 3
Negative 33 69 7
Open in a new tab

Main pooled analysis results

The pooled results with six previous published studies support an association between 4-bp ins/del polymorphism of EGLN2 and cancer susceptibility. The variant positively associated with overall cancer susceptibility in heterozygous (OR=1.38, 95 % CI=1.26-1.52, p<0.00001, ins/del vs ins/ins), homozygous (OR=1.66, 95 % CI=1.05-2.61, p=0.029, del/del vs ins/ins), codominant (OR=1.44, 95%CI=1.32-1.58, p<0.00001, ins/del+del/del vs ins/ins), and allele (OR=1.32, 95%CI=1.18-1.49, p<0.00001, del vs ins) inheritance model (Table 4 and Figure 1).

Table 4.

The Pooled ORs and 95%CIs for the Association between EGLN2 4-bp ins/del Polymorphism and Cancer Susceptibility

Genetic model Association test
 Heterogeneity test
 Publication bias
OR (95%CI) Z p χ2 I2(%) P Egger’s test p Begg’s test p
ins/del vs ins/ins 1.38 (1.26-1.52) 6.98 <0.00001 2.68 0 0.848 0.109 0.051
del/del vs ins/ins 1.66 (1.05-2.61) 2.18 0.029 21.46 72 0.002 0.115 0.099
ins/del+del/del vs ins/ins 1.44 (1.32-1.58) 8.15 <0.00001 3.61 0 0.729 0.044 0.099
del/del vs ins/del+ins/ins 1.45 (0.90-2.32 1.54 0.12 24.15 75 0 0.133 0.099
del vs ins 1.32 (1.18-1.49) 4.73 <0.00001 13.39 55 0.04 0.081 0.176
Open in a new tab

Figure 1.

Figure 1

Open in a new tab

The Forest Plot for the Relationship between EGLN2 4-bp ins/del Polymorphism and Cancer Susceptibility for ins/del vs ins/ins (A), del/del vs ins/ins (B), ins/del+del/del vs ins/ins (C), dels/del vs ins/del+del/del (D), and del vs ins (E).

Heterogeneity between the studies comprised in the pooled analysis is indicated in Table 2. The findings suggested no heterogeneity in heterozygous and dominant genetic models.

Begg’s funnel plot and Egger’s test noticed no publication bias in all genetic models except in dominant (Table 4).

We executed sensitivity analysis to evaluate the influence of each study on the overall estimate. The pooled ORs were not substantially changed except in homozygous model, indicating that the present pooled analysis is stable and reliable.

Discussion

Prolyl hydroxylases 1 (PHD1) encoded by EGLN2 gene is involved in the catalyze degradation of HIF-1 by prolyl hydroxylation of specific residues. Several studies examined the role of EGLN2 4-bp ins/del polymorphism and the risk of some cancers (Zhu et al., 2012; Che et al., 2014; Wang et al., 2014; Li et al., 2017; Hashemi et al., 2018b; Zhu et al., 2018). In the current study, for the first time, we inspected the correlation between EGLN2 4-bp ins/del polymorphism with the risk and clinicopathological characteristic of PCa. Our findings revealed no association between this variant and susceptibility as well as clinicopathological features of PCa patients. Furthermore, pooled analysis of our outcomes with six previous published studies indicated a significant association between the variant and risk of overall cancer in heterozygous, homozygous, codominant, and allele genetic models.

Long non-coding RNAs (lncRNAs), a class of non-coding transcripts longer than 200 nucleotides, are involved in epigenetic, transcriptional and post-transcriptional regulation of gene expression (Ponting et al., 2009). Growing evidence revealed that dysregulation expression of lncRNA contributes to the development and progression of various cancer for their function as proto-oncogene or anti-oncogene (Pibouin et al., 2002; Calin et al., 2007; Lin et al., 2007; He et al., 2016; Tian et al., 2016; Pei et al., 2017).

RERT-lncRNA, with 2,849 base pairs in length, is located within the proximal promoter of EGLN2, and a 4-bp ins/del polymorphism (rs10680577) is within PERT-lncRNA (Zhu et al., 2012). As rs10680577 variant is positioned within the RERT-lncRNA, it is reasonable that this variant may influence the expression level of RERT-lncRNA by affecting its folding structures. Recently, Zhu et al., (2018) reported that 4-bp ins/del polymorphism (rs10680577) affect the expression of EGLN2 and PERT-lncRNA. They found that the ins/del+del/del genotype carriers had increased expressions level of RERT-lncRNA as well as EGLN2.

In conclusion, our findings proposed that EGLN2 4-bp ins/del polymorphism was not correlated with susceptibility and clinicopathological features of PCa in an Iranian population. Pooled analysis of our findings with previously published studies designated that 4-bp ins/del variant significantly augmented the risk of overall cancer.

Acknowledgements

This study was supported by a dissertation grant (MSc thesis of NR #6802) from the deputy for Research, Zahedan University of Medical Sciences.

Conflicting Interests

The authors declare no conflict of interest.

References

  1. Appelhoff RJ, Tian YM, Raval RR, et al. Differential function of the prolyl hydroxylases PHD1, PHD2, and PHD3 in the regulation of hypoxia-inducible factor. J Biol Chem. 2004;279:38458–65. doi: 10.1074/jbc.M406026200. [DOI] [PubMed] [Google Scholar]
  2. Brahimi-Horn MC, Chiche J, Pouyssegur J. Hypoxia and cancer. J Mol Med (Berl) 2007;85:1301–7. doi: 10.1007/s00109-007-0281-3. [DOI] [PubMed] [Google Scholar]
  3. Calin GA, Liu CG, Ferracin M, et al. Ultraconserved regions encoding ncRNAs are altered in human leukemias and carcinomas. Cancer Cell. 2007;12:215–29. doi: 10.1016/j.ccr.2007.07.027. [DOI] [PubMed] [Google Scholar]
  4. Che J, Jiang D, Zheng Y, et al. Polymorphism in PHD1 gene and risk of non-small cell lung cancer in a Chinese population. Tumour Biol. 2014;35:8921–5. doi: 10.1007/s13277-014-2112-9. [DOI] [PubMed] [Google Scholar]
  5. Chokkalingam AP, Stanczyk FZ, Reichardt JK, et al. Molecular epidemiology of prostate cancer: hormone-related genetic loci. Front Biosci. 2007;12:3436–60. doi: 10.2741/2325. [DOI] [PubMed] [Google Scholar]
  6. Cunningham GR, Ashton CM, Annegers JF, et al. Familial aggregation of prostate cancer in African-Americans and white Americans. Prostate. 2003;56:256–62. doi: 10.1002/pros.10252. [DOI] [PubMed] [Google Scholar]
  7. Hashemi M, Amininia S, Ebrahimi M, et al. Association between polymorphisms in TP53 and MDM2 genes and susceptibility to prostate cancer. Oncol Lett. 2017a;13:2483–9. doi: 10.3892/ol.2017.5739. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hashemi M, Bahari G, Sarhadi S, et al. 4-bp insertion/deletion (rs3783553) polymorphism within the 3’UTR of IL1A contributes to the risk of prostate cancer in a sample of Iranian population. J Cell Biochem. 2018a;119:2627–35. doi: 10.1002/jcb.26427. [DOI] [PubMed] [Google Scholar]
  9. Hashemi M, Bahari G, Sattarifard H, et al. Evaluation of a 3-base pair indel polymorphism within pre-microRNA-3131 in patients with prostate cancer using mismatch polymerase chain reaction-restriction fragment length polymorphism. Mol Clin Oncol. 2017b;7:696–700. doi: 10.3892/mco.2017.1369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hashemi M, Danesh H, Bizhani F, et al. Detection of a 4-bp Insertion/deletion Polymorphism within the Promoter of EGLN2 Using Mismatch PCR-RFLP and Its Association with Susceptibility to Breast Cancer. Asian Pac J Cancer Prev. 2018b;19:923–6. doi: 10.22034/APJCP.2018.19.4.923. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hashemi M, Moazeni-Roodi A, Tabasi F, et al. 5-bp insertion/deletion polymorphism in the promoter region of LncRNA GAS5 and cancer risk: A meta-analysis of 7005 cases and 8576 controls. Meta Gene. 2018c;18:177–83. [Google Scholar]
  12. Hashemi M, Tabasi F, Ansari H. 4-bp insertion/deletion polymorphism within the promoter of EGLN2 gene is associated with susceptibility to cancer in Asian population: Evidence from a meta-analysis. Meta Gene. 2018d;17:141–6. [Google Scholar]
  13. He A, Chen Z, Mei H, et al. Decreased expression of LncRNA MIR31HG in human bladder cancer. Cancer Biomark. 2016;17:231–6. doi: 10.3233/CBM-160635. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90. doi: 10.3322/caac.20107. [DOI] [PubMed] [Google Scholar]
  15. Kaelin WG Jr, Ratcliffe PJ. Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. Mol Cell. 2008;30:393–402. doi: 10.1016/j.molcel.2008.04.009. [DOI] [PubMed] [Google Scholar]
  16. Li C, Feng L, Niu L, et al. An insertion/deletion polymorphism within the promoter of EGLN2 is associated with susceptibility to colorectal cancer. Int J Biol Markers. 2017;32:274–7. doi: 10.5301/jbm.5000253. [DOI] [PubMed] [Google Scholar]
  17. Lin R, Maeda S, Liu C, et al. A large noncoding RNA is a marker for murine hepatocellular carcinomas and a spectrum of human carcinomas. Oncogene. 2007;26:851–8. doi: 10.1038/sj.onc.1209846. [DOI] [PubMed] [Google Scholar]
  18. Maxwell PH, Ratcliffe PJ. Oxygen sensors and angiogenesis. Semin Cell Dev Biol. 2002;13:29–37. doi: 10.1006/scdb.2001.0287. [DOI] [PubMed] [Google Scholar]
  19. Mullaney JM, Mills RE, Pittard WS, et al. Small insertions and deletions (INDELs) in human genomes. Hum Mol Genet. 2010;19:R131–6. doi: 10.1093/hmg/ddq400. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Pei Z, Du X, Song Y, et al. Down-regulation of lncRNA CASC2 promotes cell proliferation and metastasis of bladder cancer by activation of the Wnt/beta-catenin signaling pathway. Oncotarget. 2017;8:18145–53. doi: 10.18632/oncotarget.15210. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Pezzuto A, Carico E. Role of HIF-1 in cancer progression: Novel Insights. A Review. Curr Mol Med. 2018;18:343–51. doi: 10.2174/1566524018666181109121849. [DOI] [PubMed] [Google Scholar]
  22. Pibouin L, Villaudy J, Ferbus D, et al. Cloning of the mRNA of overexpression in colon carcinoma-1: a sequence overexpressed in a subset of colon carcinomas. Cancer Genet Cytogenet. 2002;133:55–60. doi: 10.1016/s0165-4608(01)00634-3. [DOI] [PubMed] [Google Scholar]
  23. Ponting CP, Oliver PL, Reik W. Evolution and functions of long noncoding RNAs. Cell. 2009;136:629–41. doi: 10.1016/j.cell.2009.02.006. [DOI] [PubMed] [Google Scholar]
  24. Ryan DM, Vincent TL, Salit J, et al. Smoking dysregulates the human airway basal cell transcriptome at COPD risk locus 19q132. PLoS One. 2014;9:e88051. doi: 10.1371/journal.pone.0088051. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Sattarifard H, Hashemi M, Hassanzarei S, et al. Long non-coding RNA POLR2E gene polymorphisms increased the risk of prostate cancer in a sample of the Iranian population. Nucleosides Nucleotides Nucleic Acids. 2018:1–11. doi: 10.1080/15257770.2017.1391394. [DOI] [PubMed] [Google Scholar]
  26. Semenza GL. Perspectives on oxygen sensing. Cell. 1999;98:281–4. doi: 10.1016/s0092-8674(00)81957-1. [DOI] [PubMed] [Google Scholar]
  27. Semenza GL. Hypoxia-inducible factor 1 (HIF-1) pathway. Sci STKE. 2007;2007:cm8. doi: 10.1126/stke.4072007cm8. [DOI] [PubMed] [Google Scholar]
  28. Stolze IP, Mole DR, Ratcliffe PJ. Regulation of HIF: prolyl hydroxylases. Novartis Found Symp. 2006;272:15. 25; discussion -36. [PubMed] [Google Scholar]
  29. Tian T, Li C, Xiao J, et al. Quantitative Assessment of the Polymorphisms in the HOTAIR lncRNA and Cancer Risk: A Meta-Analysis of 8 Case-Control Studies. PLoS One. 2016;11:e0152296. doi: 10.1371/journal.pone.0152296. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Wang J, Zhang J, Zhou C, et al. An insertion/deletion polymorphism within the proximal promoter of EGLN2 is associated with susceptibility for gastric cancer in the Chinese population. Genet Test Mol Biomarkers. 2014;18:269–73. doi: 10.1089/gtmb.2013.0438. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Willam C, Nicholls LG, Ratcliffe PJ, et al. The prolyl hydroxylase enzymes that act as oxygen sensors regulating destruction of hypoxia-inducible factor alpha. Adv Enzyme Regul. 2004;44:75–92. doi: 10.1016/j.advenzreg.2003.11.017. [DOI] [PubMed] [Google Scholar]
  32. Zhou X, Wei L, Jiao G, et al. The association between the APE1 Asp148Glu polymorphism and prostate cancer susceptibility: a meta-analysis based on case-control studies. Mol Genet Genomics. 2015;290:281–8. doi: 10.1007/s00438-014-0916-3. [DOI] [PubMed] [Google Scholar]
  33. Zhu J, Luo JZ, Li CB. Correlations of an insertion/deletion polymorphism (rs10680577) in the RERT-lncRNA with the susceptibility, clinicopathological features, and prognosis of lung cancer. Biochem Genet. 2018;57:147–58. doi: 10.1007/s10528-018-9883-4. [DOI] [PubMed] [Google Scholar]
  34. Zhu Z, Gao X, He Y, et al. An insertion/deletion polymorphism within RERT-lncRNA modulates hepatocellular carcinoma risk. Cancer Res. 2012;72:6163–72. doi: 10.1158/0008-5472.CAN-12-0010. [DOI] [PubMed] [Google Scholar]

Articles from Asian Pacific Journal of Cancer Prevention : APJCP are provided here courtesy of West Asia Organization for Cancer Prevention

RESOURCES