Association of lnc-LAMC2-1:1 rs2147578 and CASC8 rs10505477 Polymorphisms with Risk of Childhood Acute Lymphoblastic Leukemia

  • Hashemi, Mohammad (Cellular and Molecular Research Center, Zahedan University of Medical Sciences) ;
  • Bahari, Gholamreza (Cellular and Molecular Research Center, Zahedan University of Medical Sciences) ;
  • Naderi, Majid (Department of Pediatrics, School of Medicine, Zahedan University of Medical Sciences) ;
  • Bojd, Simin Sadeghi (Department of Pediatrics, School of Medicine, Zahedan University of Medical Sciences) ;
  • Taheri, Mohsen (Genetics of Non-Communicable Disease Research Center, Zahedan University of Medical Sciences)
  • Published : 2016.11.01


Long non-coding RNAs (lncRNAs) are a novel class of non-protein coding RNAs that are involved in a wide variety of biological processes. There are limited data regarding the impact of lnc-LAMC2-1:1 rs2147578 as well as CASC8 rs10505477 T>C polymorphisms on cancer development. Here we examined for the first time whether rs2147578 and rs10505477 polymorphisms are associated with childhood acute lymphoblastic leukemia (ALL) in a total of 110 cases and 120 healthy controls. Genotyping was achieved by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The rs2147578 variant increased the risk of ALL in codominant (OR=4.33, 95%CI=2.00-9.37, p<0.0001, CG vs CC, and OR=5.81, 95%CI=2.30-14.69, p=0.0002, GG vs CC), dominant (OR=4.63, 95%CI=2.18-9.86, p<0.0001, CG+GG vs CC), overdominant (OR=1.74, 95%CI=1.02-2.97, p=0.0444, CG vs CC+GG) and allele (OR=1.91, 95%CI=1.32-2.77, p=0.0008, G vs C) inheritance models tested. No significant association was found between the CASC8 rs10505477 T>C variant and risk of childhood ALL. In conclusion, the present study revealed that the lnc-LAMC2-1:1 rs2147578 polymorphism may be a risk factor for developing childhood ALL. Further studies with larger sample sizes with different ethnicities are now required to confirm our findings.


Supported by : Zahedan University of Medical Sciences


  1. Bahari G, Hashemi M, Naderi M, et al (2016a). Association of SHMT1 gene polymorphisms with the risk of childhood acute lymphoblastic leukemia in a sample of Iranian population. Cell Mol Biol (Noisy-le-grand), 62, 45-51.
  2. Bahari G, Hashemi M, Naderi M, et al (2016b). IKZF1 gene polymorphisms increased the risk of childhood acute lymphoblastic leukemia in an Iranian population. Tumour Biol, 37, 9579-86.
  3. Bahari G, Hashemi M, Naderi M, et al (2016c). TET2 Promoter DNA Methylation and Expression in Childhood Acute Lymphoblastic Leukemia. Asian Pac J Cancer Prev, 17, 3959-62.
  4. Emmrich S, Streltsov A, Schmidt F, et al (2014). LincRNAs MONC and MIR100HG act as oncogenes in acute megakaryoblastic leukemia. Mol Cancer, 13, 171.
  5. Fernando TR, Rodriguez-Malave NI, Waters EV, et al (2015). LncRNA Expression Discriminates Karyotype and Predicts Survival in B-Lymphoblastic Leukemia. Mol Cancer Res, 13, 839-51.
  6. Geisler S, Coller J (2013). RNA in unexpected places: long noncoding RNA functions in diverse cellular contexts. Nat Rev Mol Cell Biol, 14, 699-712.
  7. Ghoussaini M, Song H, Koessler T, et al (2008). Multiple loci with different cancer specificities within the 8q24 gene desert. J Natl Cancer Inst, 100, 962-6.
  8. Gong J, Tian J, Lou J, et al (2016a). A functional polymorphism in lnc-LAMC2-1:1 confers risk of colorectal cancer by affecting miRNA binding. Carcinogenesis, 37, 443-51.
  9. Gong WJ, Yin JY, Li XP, et al (2016b). Association of wellcharacterized lung cancer lncRNA polymorphisms with lung cancer susceptibility and platinum-based chemotherapy response. Tumour Biol, 37, 8349-58.
  10. Gupta RA, Shah N, Wang KC, et al (2010). Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature, 464, 1071-6.
  11. Han L, Zhang K, Shi Z, et al (2012). LncRNA pro fi le of glioblastoma reveals the potential role of lncRNAs in contributing to glioblastoma pathogenesis. Int J Oncol, 40, 2004-12.
  12. Hao S, Shao Z (2015). HOTAIR is upregulated in acute myeloid leukemia and that indicates a poor prognosis. Int J Clin Exp Pathol, 8, 7223-8.
  13. Hasani SS, Hashemi M, Eskandari-Nasab E, et al (2014). A functional polymorphism in the miR-146a gene is associated with the risk of childhood acute lymphoblastic leukemia: a preliminary report. Tumour Biol, 35, 219-25.
  14. Hashemi M, Bahari G, Naderi M, et al (2016). Pri-miR-34b/crs4938723 polymorphism is associated with the risk of childhood acute lymphoblastic leukemia. Cancer Genet, 209, 493-6.
  15. Hashemi M, Hanafi Bojd H, Eskandari Nasab E, et al (2013). Association of Adiponectin rs1501299 and rs266729 Gene Polymorphisms With Nonalcoholic Fatty Liver Disease. Hepat Mon, 13, e9527.
  16. Hauptman N, Glavac D (2013). Long non-coding RNA in cancer. Int J Mol Sci, 14, 4655-69.
  17. He J, Wilkens LR, Stram DO, et al (2011). Generalizability and epidemiologic characterization of eleven colorectal cancer GWAS hits in multiple populations. Cancer Epidemiol Biomarkers Prev, 20, 70-81.
  18. Hu L, Chen SH, Lv QL, et al (2016). Clinical significance of long non-coding RNA CASC8 rs10505477 polymorphism in lung cancer susceptibility, platinum-based chemotherapy response, and toxicity. Int J Environ Res Public Health, 13, 545.
  19. Kang M, Sang Y, Gu H, et al (2015). Long noncoding RNAs POLR2E rs3787016 C/T and HULC rs7763881 A/C polymorphisms are associated with decreased risk of esophageal cancer. Tumour Biol, 36, 6401-8.
  20. Kung JT, Colognori D, Lee JT (2013). Long noncoding RNAs: past, present, and future. Genetics, 193, 651-69.
  21. Li L, Jia F, Bai P, et al (2016). Association between polymorphisms in long non-coding RNA PRNCR1 in 8q24 and risk of gastric cancer. Tumour Biol, 37, 299-303.
  22. Li L, Lv L, Liang Y, et al (2015). Association of 8q23-24 region (8q23.3 loci and 8q24.21 loci) with susceptibility to colorectal cancer: a systematic and updated meta-analysis. Int J Clin Exp Med, 8, 21001-13.
  23. Ma G, Gu D, Lv C, et al (2015). Genetic variant in 8q24 is associated with prognosis for gastric cancer in a Chinese population. J Gastroenterol Hepatol, 30, 689-95.
  24. Morlando M, Ballarino M, Fatica A (2015). Long Non-Coding RNAs: New Players in Hematopoiesis and Leukemia. Front Med (Lausanne), 2, 23.
  25. Morris KV (2009). Long antisense non-coding RNAs function to direct epigenetic complexes that regulate transcription in human cells. Epigenetics, 4, 296-301.
  26. Qi P, Du X (2013). The long non-coding RNAs, a new cancer diagnostic and therapeutic gold mine. Mod Pathol, 26, 155-65.
  27. Ricciuti B, Mencaroni C, Paglialunga L, et al (2016). Long noncoding RNAs: new insights into non-small cell lung cancer biology, diagnosis and therapy. Med Oncol, 33, 18.
  28. Rinn JL, Chang HY (2012). Genome regulation by long noncoding RNAs. Annu Rev Biochem, 81, 145-66.
  29. Rodriguez-Malave NI, Fernando TR, Patel PC, et al (2015). BALR-6 regulates cell growth and cell survival in B-lymphoblastic leukemia. Mol Cancer, 14, 214.
  30. Ronchetti D, Agnelli L, Taiana E, et al (2016). Distinct lncRNA transcriptional fingerprints characterize progressive stages of multiple myeloma. Oncotarget, 7, 14814-30.
  31. Shang C, Guo Y, Zhang H, et al (2016). Long noncoding RNA HOTAIR is a prognostic biomarker and inhibits chemosensitivity to doxorubicin in bladder transitional cell carcinoma. Cancer Chemother Pharmacol, 77, 507-13.
  32. Shen L, Du M, Wang C, et al (2014). Clinical significance of POU5F1P1 rs10505477 polymorphism in Chinese gastric cancer patients receving cisplatin-based chemotherapy after surgical resection. Int J Mol Sci, 15, 12764-77.
  33. Siegel R, Naishadham D, Jemal A (2013). Cancer statistics, 2013. CA Cancer J Clin, 63, 11-30.
  34. Sun QL, Zhao CP, Wang TY, et al (2015). Expression profile analysis of long non-coding RNA associated with vincristine resistance in colon cancer cells by next-generation sequencing. Gene, 572, 79-86.
  35. Tomlinson I, Webb E, Carvajal-Carmona L, et al (2007). A genome-wide association scan of tag SNPs identifies a susceptibility variant for colorectal cancer at 8q24.21. Nat Genet, 39, 984-8.
  36. Tong N, Chu H, Wang M, et al (2016). Pri-miR-34b/c rs4938723 polymorphism contributes to acute lymphoblastic leukemia susceptibility in Chinese children. Leuk Lymphoma, 57, 1436-41.
  37. Tripathi V, Ellis JD, Shen Z, et al (2010). The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation. Mol Cell, 39, 925-38.
  38. Xing CY, Hu XQ, Xie FY, et al (2015). Long non-coding RNA HOTAIR modulates c-KIT expression through sponging miR-193a in acute myeloid leukemia. FEBS Lett, 589, 1981-7.
  39. Yang X, Song JH, Cheng Y, et al (2014). Long non-coding RNA HNF1A-AS1 regulates proliferation and migration in oesophageal adenocarcinoma cells. Gut, 63, 881-90.
  40. Yao K, Hua L, Wei L, et al (2015). Correlation Between CASC8, SMAD7 Polymorphisms and the Susceptibility to Colorectal Cancer: An Updated Meta-Analysis Based on GWAS Results. Medicine (Baltimore), 94, e1884.
  41. Zanke BW, Greenwood CM, Rangrej J, et al (2007). Genomewide association scan identifies a colorectal cancer susceptibility locus on chromosome 8q24. Nat Genet, 39, 989-94.
  42. Zeng C, Yu X, Lai J, et al (2015). Overexpression of the long non-coding RNA PVT1 is correlated with leukemic cell proliferation in acute promyelocytic leukemia. J Hematol Oncol, 8, 126.
  43. Zhou CP, Pan HZ, Li FX, et al (2014). Association analysis of colorectal cancer susceptibility variants with gastric cancer in a Chinese Han population. Genet Mol Res, 13, 3673-80