Advertisement

Tumor Biology

, Volume 37, Issue 5, pp 6647–6652 | Cite as

Combinations of FUT2 gene polymorphisms and environmental factors are associated with oral cancer risk

  • Kuo-Jung Su
  • Chuan-Chen Ho
  • Chiao-Wen Lin
  • Mu-Kuan Chen
  • Shih-Chi Su
  • Yung-Luen Yu
  • Shun-Fa Yang
Original Article
  • 212 Downloads

Abstract

In humans, fucosyltransferase-2 (FUT2) plays an important role in α1,2- linkage of fucose and participates in complex cellular processes such as fertilization, embryogenesis, and immune responses. However, little information is available concerning the FUT2 expression in tumorigenesis. The aim of this work was to investigate the combined effect of FUT2 gene polymorphisms and exposure to environmental carcinogens on the susceptibility and clinic pathological characteristics of oral cancer. Four SNPs of the FUT2 gene (rs281377, rs1047781, rs601338, and rs602662) from 1200 non-cancer controls and 700 oral squamous cell carcinoma (OSCC) patients were analyzed by real-time polymerase chain reaction (PCR). The samples were further analyzed to clarify the associations between these gene polymorphisms and the risk of OSCC, and the impact of these SNPs on the susceptibility and clinic pathological characteristics of OSCC. After adjusting for other covariant, we observed that betel quid chewing among 1255 smokers who carrying at least one C genotype (TC and CC) at rs281377 and least one T genotype (TA and TT) at rs1047781 were exhibited synergistic effects of environmental factors (betel quid and cigarette use) on the susceptibility of oral cancer. Taken together, our results support gene–environment interactions of FUT2 polymorphisms with smoking and betel quid chewing habits possibly altering oral cancer susceptibility. Furthermore, to our knowledge, this is the first study of association between FUT2 gene variants and OSCC risk.

Keywords

Oral cancer Fucosyltransferase-2 Single-nucleotide polymorphisms 

Notes

Acknowledgments

This study was supported by funding from Ministry of Science and Technology, Taiwan (MOST103 2320-B-039-052-MY3; MOST104-2321-B-039-005), and National Health Research Institutes, Taiwan (NHRI-EX102-10245BI).

Compliance with ethical standards

Competing interests

The authors have declared that no competing interests exist.

References

  1. 1.
    Wang YY, Tail YH, Wang WC, Chen CY, Kao YH, Chen YK, et al. Malignant transformation in 5071 southern Taiwanese patients with potentially malignant oral mucosal disorders. BMC Oral Health. 2014;14:99.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Bettendorf O, Piffko J, Bankfalvi A. Prognostic and predictive factors in oral squamous cell cancer: important tools for planning individual therapy? Oral Oncol. 2004;40:110–9.CrossRefPubMedGoogle Scholar
  3. 3.
    Biolchini F, Pollastri G, Figurelli S, Chiarini L. Carcinogen metabolism, DNA damage repair and oral head and neck squamocellular carcinoma (hnscc). A review. Minerva Stomatol. 2005;54:405–14.PubMedGoogle Scholar
  4. 4.
    Schwartz SM, Doody DR, Fitzgibbons ED, Ricks S, Porter PL, Chen C. Oral squamous cell cancer risk in relation to alcohol consumption and alcohol dehydrogenase-3 genotypes. Cancer Epidemiol, Biomarkers Prev: Publ Am Assoc Cancer Res, Cosponsored Am Soc Prev Oncol. 2001;10:1137–44.Google Scholar
  5. 5.
    Shastry BS. Snp alleles in human disease and evolution. J Hum Genet. 2002;47:561–6.CrossRefPubMedGoogle Scholar
  6. 6.
    Yu YL, Su KJ, Hsieh YH, Lee HL, Chen TY, Hsiao PC, et al. Effects of ezh2 polymorphisms on susceptibility to and pathological development of hepatocellular carcinoma. PLoS One. 2013;8, e74870.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Lin CW, Yang SF, Chuang CY, Lin HP, Hsin CH. Association of matrix metalloproteinase-11 polymorphisms with susceptibility and clinicopathologic characteristics for oral squamous cell carcinoma. Head Neck 2014.Google Scholar
  8. 8.
    Duell EJ, Bonet C, Munoz X, Lujan-Barroso L, Weiderpass E, Boutron-Ruault MC, et al. Variation at abo histo-blood group and fut loci and diffuse and intestinal gastric cancer risk in a european population. Int J Cancer J Int du Cancer. 2015;136:880–93.CrossRefGoogle Scholar
  9. 9.
    Rupp C, Friedrich K, Folseraas T, Wannhoff A, Bode KA, Weiss KH, et al. Fut2 genotype is a risk factor for dominant stenosis and biliary candida infections in primary sclerosing cholangitis. Aliment Pharmacol Ther. 2014;39:873–82.CrossRefPubMedGoogle Scholar
  10. 10.
    Ferrer-Admetlla A, Sikora M, Laayouni H, Esteve A, Roubinet F, Blancher A, et al. A natural history of fut2 polymorphism in humans. Mol Biol Evol. 2009;26:1993–2003.CrossRefPubMedGoogle Scholar
  11. 11.
    Campi C, Escovich L, Moreno A, Racca L, Racca A, Cotorruelo C, et al. Expression of the gene encoding secretor type galactoside 2 alpha fucosyltransferase (fut2) and abh antigens in patients with oral lesions. Medicina Oral, Patologia Oral y cirugia Bucal. 2012;17:e63–68.CrossRefPubMedGoogle Scholar
  12. 12.
    Folseraas T, Melum E, Rausch P, Juran BD, Ellinghaus E, Shiryaev A, et al. Extended analysis of a genome-wide association study in primary sclerosing cholangitis detects multiple novel risk loci. J Hepatol. 2012;57:366–75.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Kelly RJ, Rouquier S, Giorgi D, Lennon GG, Lowe JB. Sequence and expression of a candidate for the human secretor blood group alpha(1,2)fucosyltransferase gene (fut2). Homozygosity for an enzyme-inactivating nonsense mutation commonly correlates with the non-secretor phenotype. J Biol Chem. 1995;270:4640–9.CrossRefPubMedGoogle Scholar
  14. 14.
    McGovern DP, Jones MR, Taylor KD, Marciante K, Yan X, Dubinsky M, et al. International IBDGC: fucosyltransferase 2 (fut2) non-secretor status is associated with crohn’s disease. Hum Mol Genet. 2010;19:3468–76.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Serpa J, Mendes N, Reis CA, Santos Silva LF, Almeida R, Le Pendu J, et al. Two new fut2 (fucosyltransferase 2 gene) missense polymorphisms, 739 ga and 839 tc, are partly responsible for non-secretor status in a caucasian population from northern portugal. Biochem J. 2004;383:469–74.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Hu DY, Shao XX, Xu CL, Xia SL, Yu LQ, Jiang LJ, et al. Associations of fut2 and fut3 gene polymorphisms with crohn’s disease in chinese patients. J Gastroenterol Hepatol. 2014;29:1778–85.CrossRefPubMedGoogle Scholar
  17. 17.
    Koda Y, Soejima M, Kimura H. The polymorphisms of fucosyltransferases. Legal Med. 2001;3:2–14.CrossRefPubMedGoogle Scholar
  18. 18.
    Lin FY, Lin CW, Yang SF, Lee WJ, Lin YW, Lee LM, et al. Interactions between environmental factors and melatonin receptor type 1a polymorphism in relation to oral cancer susceptibility and clinicopathologic development. PLoS One. 2015;10, e0121677.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Chien MH, Yang JS, Chu YH, Lin CH, Wei LH, Yang SF, et al. Impacts of ca9 gene polymorphisms and environmental factors on oral-cancer susceptibility and clinicopathologic characteristics in taiwan. PLoS One. 2012;7, e51051.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Yen TT, Lin WD, Wang CP, Wang CC, Liu SA. The association of smoking, alcoholic consumption, betel quid chewing and oral cavity cancer: a cohort study. Eur Archives Oto-Rhino-Laryngology: Off J Eur Fed Oto-Rhino-Laryngological Soc. 2008;265:1403–7.CrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Kuo-Jung Su
    • 1
  • Chuan-Chen Ho
    • 2
    • 3
  • Chiao-Wen Lin
    • 3
    • 4
  • Mu-Kuan Chen
    • 5
    • 6
  • Shih-Chi Su
    • 7
  • Yung-Luen Yu
    • 1
    • 8
    • 9
  • Shun-Fa Yang
    • 5
    • 10
  1. 1.The Ph.D. Program for Cancer Biology and Drug DiscoveryChina Medical University and Academia SinicaTaichungTaiwan
  2. 2.School of DentistryChung Shan Medical UniversityTaichungTaiwan
  3. 3.Department of DentistryChung Shan Medical University HospitalTaichungTaiwan
  4. 4.Institute of Oral SciencesChung Shan Medical UniversityTaichungTaiwan
  5. 5.Institute of MedicineChung Shan Medical UniversityTaichungTaiwan
  6. 6.Department of Otorhinolaryngology-Head and Neck SurgeryChanghua Christian HospitalChanghuaTaiwan
  7. 7.Whole-Genome Research Core Laboratory of Human DiseasesChang Gung Memorial HospitalKeelungTaiwan
  8. 8.Graduate Institute of Cancer Biology, and Center for Molecular MedicineChina Medical UniversityTaichungTaiwan
  9. 9.Department of BiotechnologyAsia UniversityTaichungTaiwan
  10. 10.Department of Medical ResearchChung Shan Medical University HospitalTaichungTaiwan

Personalised recommendations