The role of genetic polymorphisms of regulatory T cell in synchronous cancers over upper aerodigestive tract (UADT)

  • 林 孟穎

Student thesis: Master's Thesis

Abstract

Background: Head and neck squamous cell carcinoma (HNSCC) is a highly prevalent malignant disease worldwide It is commonly associated with synchronous esophageal squamous cell carcinoma (SCC) due to similar carcinogens exposure such as cigarette smoking and alcohol drinking When the two cancers developed simultaneously so called synchronous SCC the outcome is extremely poorer than either one alone Therefore it is important to diagnose synchronous SCC in the early stages In addition to the documented risk factors such as smoking drinking and hypopharyngeal location of head and neck cancer recent study showed aberrant regulatory T cell (Treg) infiltration may contribute to the development of synchronous SCC of upper aerodigestive tract FOXP3 is a master regulator of Treg development and function We aimed to investigate whether genetic polymorphism in FOXP3 is associated with aberrant Treg infiltration risk of synchronous SCC and patient survival in HNSCC patients Methods: We consecutively enrolled HNSCC patients who received screening esophagogastroduodenoscopy from 2009 to 2016 in National Cheng Kung University Hospital and E-DA Hospital Three tag single nucleotide polymorphisms (rs2232365 rs3761548 and rs3761549) were selected from Hapmap database of Chinese Han group Patients’ DNA was extracted from peripheral lymphocyte and genotyped by real-time PCR Treg infiltration in tumor tissue was evaluated by immunohistochemistry The association between FOXP3 genotypes and synchronous SCC risk patient prognosis and Treg infiltration were analyzed Result: A Total of 270 patients with matched gender (male only because female was extremely rare) smoking and alcohol usage state were included for final analyses (135 with HNSCC alone and 135 with synchronous SCC) We confirmed that hypopharyngeal location of HNSCC significantly correlated to synchronous SCC development (p = 0 012 OR = 1 87) In the 3 selected tag-SNPs rs3761549 G allele was significantly associated with increased synchronous SCC risk (OR = 2 205 95%CI 1 215-4 002 p = 0 009) After adjusting HNSCC location and HNSCC tumor stage rs3761549 G allele was an independent risk factor for synchronous SCC (aOR=2 10 95% CI 1 105-4 002 p = 0 024) There was highly linkage between the 3 tag-SNPs and Haplotype C-G-A (rs2232365/3761548/3761549) also significantly protected from synchronous SCC development (OR=0 453 95% CI 0 250-0 823 p = 0 009) In addition patient with G allele in rs3761549 had significantly higher FOXP3+ Treg infiltration in the tumor tissue (mean FOXP3+ cell number/mm2 55 93 vs 36 39 p = 0 008) Patients carrying G allele in rs3761549 also had a trend of poorer overall survival in the subgroup of late-stage HNSCC (G allele vs A allele 41 5 +/- 3 6 months vs 46 6 +/- 5 1 months) Conclusion: Male HNSCC patients who carries G allele in rs3761549 of the FOXP3 gene has a higher risk for synchronous SCC development and trend of poorer outcome They warrant intensive EGD checkup to diagnose synchronous cancer as early
Date of Award2018 Sep 4
LanguageEnglish
SupervisorBor-Shyang Sheu (Supervisor)

Cite this

The role of genetic polymorphisms of regulatory T cell in synchronous cancers over upper aerodigestive tract (UADT)
孟穎, 林. (Author). 2018 Sep 4

Student thesis: Master's Thesis