title: MicroRNA-related genetic variations as predictors for risk of second primary tumor and/or recurrence in patients with early-stage head and neck cancer.
abstract: Second primary tumor (SPT) and/or recurrence negatively impact the prognosis of patients with curatively treated early-stage head and neck cancer. MicroRNAs (miRNAs) play important roles in cancer development. We explored whether the variations of miRNA-related pathway were associated with the risk of SPT/recurrence in patients with early-stage head and neck cancer. This study includes 150 early-stage head and neck cancer patients with SPT/recurrence and 300 patients without SPT/recurrence. Two hundred and thirty-five tagging and potentially functional single-nucleotide polymorphisms (SNPs) were genotyped from eight miRNA biogenesis pathway genes and 135 miRNA-targeted genes. Eighteen miRNA-related SNPs were significantly associated with the risk of SPT/recurrence. The most significant SNP was rs3747238, a miRNA-binding site SNP in SMC1B. The variant homozygous genotype of this SNP was associated with a 1.74-fold increased risk [95% confidence interval (CI) 1.19-2.54; P = 0.004]. Cumulative effect analysis showed joint effects for the number of unfavorable genotype in patients. Survival tree analysis further identified the high-order gene-gene interactions and categorized the study subjects into low-, medium- and high-risk groups. Patients in the high-risk group had a 4.84-fold increased risk (95% CI: 3.11-7.51; P = 2.45 × 10(-12)) and a shorter event-free median survival time of 37.9 months (log rank P = 2.28 × 10(-13)). Our results suggested that miRNA-related genetic polymorphisms may be used individually and jointly to predict the risk of SPT/recurrence of early-stage head and neck cancer patients.
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Xiaofan
authors.initials: X
authors.lastname: Zhang
authors.forename: Hushan
authors.initials: H
authors.lastname: Yang
authors.forename: J Jack
authors.initials: JJ
authors.lastname: Lee
authors.forename: Edward
authors.initials: E
authors.lastname: Kim
authors.forename: Scott M
authors.initials: SM
authors.lastname: Lippman
authors.forename: Fadlo R
authors.initials: FR
authors.lastname: Khuri
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Spitz
authors.forename: Reuben
authors.initials: R
authors.lastname: Lotan
authors.forename: Waun K
authors.initials: WK
authors.lastname: Hong
authors.forename: Xifeng
authors.initials: X
authors.lastname: Wu
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics; D014644:Genetic Variation; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D028884:Karyopherins / Q000235:genetics; D035683:MicroRNAs / Q000502:physiology*; D009364:Neoplasm Recurrence, Local / Q000209:etiology / Q000235:genetics*; D009367:Neoplasm Staging; D016609:Neoplasms, Second Primary / Q000209:etiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D000098550:Structural Maintenance of Chromosome Protein 1
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D028884:Karyopherins; D035683:MicroRNAs; C446511:XPO5 protein, human; D000098550:Structural Maintenance of Chromosome Protein 1
references.citation: Cancer Res. 2008 Apr 1;68(7):2530-7
references.pmid: 18381463
references.citation: Methods Mol Biol. 2006;342:33-47
references.pmid: 16957365
references.citation: Biochim Biophys Acta. 2008 Nov;1779(11):663-7
references.pmid: 18778799
references.citation: Cancer Causes Control. 2003 Mar;14(2):131-8
references.pmid: 12749718
references.citation: Cancer Prev Res (Phila). 2009 Jul;2(7):617-24
references.pmid: 19584075
references.citation: RNA. 2009 Jun;15(6):1005-11
references.pmid: 19383765
references.citation: Cancer Epidemiol Biomarkers Prev. 2007 Jan;16(1):178-81
references.pmid: 17220350
references.citation: Science. 2004 Jan 2;303(5654):95-8
references.pmid: 14631048
references.citation: Nature. 2005 Jun 9;435(7043):834-8
references.pmid: 15944708
references.citation: Biol Cell. 2004 Oct;96(8):639-55
references.pmid: 15519698
references.citation: Nat Cell Biol. 2004 Jun;6(6):555-62
references.pmid: 15146193
references.citation: Oncogene. 2008 Mar 27;27(14):2015-26
references.pmid: 17922033
references.citation: Biochem Biophys Res Commun. 2009 Oct 23;388(3):483-9
references.pmid: 19654003
references.citation: Proc Natl Acad Sci U S A. 2007 Aug 14;104(33):13513-8
references.pmid: 17686970
references.citation: Cell. 2009 Jan 9;136(1):75-84
references.pmid: 19135890
references.citation: Mol Cell Biol. 2009 Jun;29(12):3243-54
references.pmid: 19349299
references.citation: Adv Cancer Res. 2008;101:29-43
references.pmid: 19055941
references.citation: Cancer Cell. 2008 Jan;13(1):48-57
references.pmid: 18167339
references.citation: Genes Chromosomes Cancer. 2007 Apr;46(4):336-47
references.pmid: 17243163
references.citation: Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2006 Nov;150(2):205-15
references.pmid: 17426780
references.citation: Breast Cancer Res Treat. 2010 Jun;121(2):485-96
references.pmid: 19856098
references.citation: DNA Cell Biol. 2007 May;26(5):283-92
references.pmid: 17504024
references.citation: Cancer Cell. 2006 Mar;9(3):189-98
references.pmid: 16530703
references.citation: CA Cancer J Clin. 2009 Jul-Aug;59(4):225-49
references.pmid: 19474385
references.citation: Carcinogenesis. 2009 Jun;30(6):1003-7
references.pmid: 19380522
references.citation: Arch Toxicol. 2009 Apr;83(4):351-6
references.pmid: 18668224
references.citation: N Engl J Med. 2008 Dec 18;359(25):2641-50
references.pmid: 19092150
references.citation: Oncogene. 2004 Aug 23;23(38):6500-23
references.pmid: 15322521
references.citation: Int J Radiat Oncol Biol Phys. 1989 Sep;17(3):449-56
references.pmid: 2674073
references.citation: Cancer Prev Res (Phila). 2008 Nov;1(6):460-9
references.pmid: 19138993
references.citation: Cancer Res. 2005 May 1;65(9):3509-12
references.pmid: 15867338
references.citation: Cancer Epidemiol Biomarkers Prev. 2001 Aug;10(8):823-9
references.pmid: 11489748
references.citation: Genome Res. 2004 Oct;14(10A):1902-10
references.pmid: 15364901
references.citation: Curr Biol. 2005 Jan 26;15(2):R61-4
references.pmid: 15668159
references.citation: N Engl J Med. 2005 Oct 27;353(17):1793-801
references.pmid: 16251535
references.citation: Cytogenet Cell Genet. 2000;91(1-4):234-8
references.pmid: 11173863
references.citation: Nat Methods. 2006 Jan;3(1):31-3
references.pmid: 16369550
references.citation: Nucleic Acids Res. 2006;34(17):4711-21
references.pmid: 16963774
references.citation: Cell. 2005 Nov 18;123(4):631-40
references.pmid: 16271387
references.citation: J Am Acad Dermatol. 2008 Nov;59(5):725-37; quiz 738-40
references.pmid: 19119093
references.citation: Clin Cancer Res. 2008 Dec 1;14(23):7956-62
references.pmid: 19047128
references.citation: Cancer Epidemiol Biomarkers Prev. 2003 Aug;12(8):689-98
references.pmid: 12917198
references.citation: Clin Cancer Res. 2006 Dec 1;12(23):7194-201
references.pmid: 17145846
references.citation: Head Neck. 2002 Feb;24(2):198-206
references.pmid: 11891950
references.citation: Int J Cancer. 2009 Jun 15;124(12):2855-63
references.pmid: 19347935
references.citation: Ann Otol Rhinol Laryngol. 1992 Feb;101(2 Pt 1):105-12
references.pmid: 1531402