Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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The rs61764370 Functional Variant in the KRAS Oncogene is Associated with Chronic Myeloid Leukemia Risk in Women

  • Published : 2016.06.01
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Abstract

Background: Chronic myeloid leukemia (CML) is one of the most frequent hematopoietic malignancies in the elderly population; however, knowledge is limited regarding the genetic factors associated with increased risk for CML. Polymorphisms affecting microRNA (miRNA) biogenesis or mRNA:miRNA interactions are important risk factors in the development of different types of cancer. Thus, we carried out a case-control study to test the association with CML susceptibility of gene variants located in the miRNA machinery genes AGO1 (rs636832) and GEMIN4 (rs2740348), as well as in the miRNA binding sites of the genes BRCA1 (rs799917) and KRAS (rs61764370). Materials and Methods: We determined the genotype of 781 Mexican-Mestizo individuals (469 healthy subjects and 312 CML cases) for the four polymorphisms using TaqMan probes to test the association with CML susceptibility. Results: We found a borderline association of the minor homozygote genotype of the KRAS_rs61764370 polymorphism with an increased risk for CML susceptibility (P = 0.06). After gender stratification, this association was significant only for women (odds ratio [OR] = 13.41, P = 0.04). The distribution of the allelic and genotypic frequencies of the four studied SNPs was neither associated with advanced phases of CML nor treatment response. Conclusions: To the best of our knowledge, this study is the first to show a significant association of the KRAS_rs61764370 SNP with CML. To further determine such an association of with CML susceptibility, our results must be replicated in different ethnic groups.

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References

  1. Apperley JF (2015). Chronic myeloid leukaemia. Lancet, 385, 1447-59. https://doi.org/10.1016/S0140-6736(13)62120-0
  2. Copley MR, Babovic S, Benz C, et al (2013). The Lin28b-let-7- Hmga2 axis determines the higher self-renewal potential of fetal haematopoietic stem cells. Nat Cell Biol, 15, 916-25. https://doi.org/10.1038/ncb2783
  3. Chandra P, Luthra R, Zuo Z, et al (2010). Acute myeloid leukemia with t(9;11)(p21-22;q23): common properties of dysregulated ras pathway signaling and genomic progression characterize de novo and therapy-related cases. Am J Clin Pathol, 133, 686-93. https://doi.org/10.1309/AJCPGII1TT4NYOGI
  4. Chin LJ, Ratner E, Leng S, et al (2008). A SNP in a let-7 microRNA complementary site in the KRAS 3' untranslated region increases non-small cell lung cancer risk. Cancer Res, 68, 8535-40. https://doi.org/10.1158/0008-5472.CAN-08-2129
  5. Dimas AS, Nica AC, Montgomery SB, et al (2012). Sex-biased genetic effects on gene regulation in humans. Genome Res, 22, 2368-75. https://doi.org/10.1101/gr.134981.111
  6. Genomes Project C, Abecasis GR, Auton A, et al (2012). An integrated map of genetic variation from 1,092 human genomes. Nature, 491, 56-65. https://doi.org/10.1038/nature11632
  7. Ha M, Kim VN (2014). Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol, 15, 509-24. https://doi.org/10.1038/nrm3838
  8. Horikawa Y, Wood CG, Yang H, et al (2008). Single nucleotide polymorphisms of microRNA machinery genes modify the risk of renal cell carcinoma. Clin Cancer Res, 14, 7956-62. https://doi.org/10.1158/1078-0432.CCR-08-1199
  9. Kim JS, Choi YY, Jin G, et al (2010). Association of a common AGO1 variant with lung cancer risk: a two-stage case-control study. Mol Carcinog, 49, 913-21. https://doi.org/10.1002/mc.20672
  10. Kjersem JB, Ikdahl T, Guren T, et al (2012). Let-7 miRNAbinding site polymorphism in the KRAS 3'UTR; colorectal cancer screening population prevalence and influence on clinical outcome in patients with metastatic colorectal cancer treated with 5-fluorouracil and oxaliplatin +/- cetuximab. BMC Cancer, 12, 534. https://doi.org/10.1186/1471-2407-12-534
  11. Knight T, Irving JA (2014). Ras/Raf/MEK/ERK Pathway Activation in Childhood Acute Lymphoblastic Leukemia and Its Therapeutic Targeting. Front Oncol, 4, 160.
  12. Kuang WJ, Sun RF, Zhu YS, et al (2011). A new singlenucleotide mutation (rs362719) of the reelin (RELN) gene associated with schizophrenia in female Chinese Han. Genet Mol Res, 10, 1650-8. https://doi.org/10.4238/vol10-3gmr1343
  13. Liu J, Liu J, Wei M, et al (2012). Genetic variants in the microRNA machinery gene GEMIN4 are associated with risk of prostate cancer: a case-control study of the Chinese Han population. DNA Cell Biol, 31, 1296-302. https://doi.org/10.1089/dna.2011.1600
  14. Nicoloso MS, Sun H, Spizzo R, et al (2010). Single-nucleotide polymorphisms inside microRNA target sites influence tumor susceptibility. Cancer Res, 70, 2789-98. https://doi.org/10.1158/0008-5472.CAN-09-3541
  15. Ober C, Loisel DA, Gilad Y (2008). Sex-specific genetic architecture of human disease. Nat Rev Genet, 9, 911-22. https://doi.org/10.1038/nrg2415
  16. Paranjape T, Heneghan H, Lindner R, et al (2011). A 3'-untranslated region KRAS variant and triple-negative breast cancer: a case-control and genetic analysis. Lancet Oncol, 12, 377-86. https://doi.org/10.1016/S1470-2045(11)70044-4
  17. Radich J (2014). Structure, function, and resistance in chronic myeloid leukemia. Cancer Cell, 26, 305-6. https://doi.org/10.1016/j.ccr.2014.08.010
  18. Ratner E, Lu L, Boeke M, et al (2010). A KRAS-variant in ovarian cancer acts as a genetic marker of cancer risk. Cancer Res, 70, 6509-15. https://doi.org/10.1158/0008-5472.CAN-10-0689
  19. Samatar AA, Poulikakos PI (2014). Targeting RAS-ERK signalling in cancer: promises and challenges. Nat Rev Drug Discov, 13, 928-42. https://doi.org/10.1038/nrd4281
  20. Shang M, Huang Y, Hu X, et al (2014). Association between SNPs in miRNA-machinery genes and chronic hepatitis B in the Chinese Han population. Infect Genet Evol, 28, 113-7. https://doi.org/10.1016/j.meegid.2014.09.015
  21. Ursan ID, Jiang R, Pickard EM, et al (2015). Emergence of BCR-ABL kinase domain mutations associated with newly diagnosed chronic myeloid leukemia: a meta-analysis of clinical trials of tyrosine kinase inhibitors. J Manag Care Spec Pharm, 21, 114-22. https://doi.org/10.18553/jmcp.2015.21.2.114
  22. Wang K, Xu L, Pan L, et al (2015). The functional BRCA1 rs799917 genetic polymorphism is associated with gastric cancer risk in a Chinese Han population. Tumour Biol, 36, 393-7. https://doi.org/10.1007/s13277-014-2655-9
  23. Zhang X, Wei J, Zhou L, et al (2013). A functional BRCA1 coding sequence genetic variant contributes to risk of esophageal squamous cell carcinoma. Carcinogenesis, 34, 2309-13. https://doi.org/10.1093/carcin/bgt213
  24. Zhao W, Wang Y, Wang L, et al (2009). Gender-specific association between the kininogen 1 gene variants and essential hypertension in Chinese Han population. J Hypertens, 27, 484-90. https://doi.org/10.1097/HJH.0b013e32831e19f9
  25. Zhao Z, Chen CC, Rillahan CD, et al (2015). Cooperative loss of RAS feedback regulation drives myeloid leukemogenesis. Nat Genet, 47, 539-43. https://doi.org/10.1038/ng.3251