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  • [Clin Cancer Res.] TGFβ1 Genetic Variants Predict Clinical Outcomes of HPV-Positive Oropharyngeal Cancer Patients after Definitive Radiotherapy.

    MD Anderson Cancer Center, Beijing Tongren Hospital / Guojun Li*, Zhigang Huang*

  • 출처
    Clin Cancer Res.
  • 등재일
    2018 May 1
  • 저널이슈번호
    24(9):2225-2233. doi: 10.1158/1078-0432.CCR-17-1904. Epub 2018 Feb 20.
  • 내용

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    Abstract
    Purpose: TGFβ1 plays a critical role in inflammation and immune responses and treatment response and survival. TGFβ1 variants may affect its expression level or functional efficiency, thus modifying tumor status and survival in human papillomavirus (HPV)-positive squamous cell carcinoma of the oropharynx (SCCOP).Experimental Design: We determined tumor HPV16 status and genotyped three TGFβ1 polymorphisms in 564 incident SCCOP patients treated with radiotherapy or chemoradiation. Univariate and multivariable Cox models were used to evaluate the associations between the three polymorphisms and survival.Results: Overall, 85% of patients (482 of 564) had HPV16-positive SCCOP. We found that TGFβ1 rs1982073 had statistically significant associations with survival, whereas TGFβ1 rs1800469 and TGFβ1 rs1800471 did not. Patients with TGFβ1 rs1982073 CT/CC variant genotypes had significantly better overall, disease-specific, and disease-free survival compared with those with the corresponding common homozygous TT genotype (all log-rank: P < 0.001). Furthermore, these genotypes were significantly associated with an approximately 5 times reduced risk of overall death, death owing to disease, and recurrence after multivariable adjustment. Moreover, the stratified analyses by tumor HPV status indicated that the significant effects of TGFβ1 rs1982073 polymorphism on survival were found among HPV16-positive SCCOP patients only. Finally, the functional relevance of these variants was further characterized.Conclusions: Our findings support that the TGFβ1 rs1982073 polymorphism plays a significant role in the prognosis of SCCOP, especially in HPV16-positive SCCOP patients treated with chemoradiation. Prospective studies with larger sample sizes are needed to confirm these findings.

     


    Author information

    Tao Y1,2,3, Sturgis EM2,4, Huang Z5, Wang Y6, Wei P7, Wang JR2, Wei Q8, Li G9,4.
    1
    Department of Otolaryngology-Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Key Laboratory of Otolaryngology Head and Neck Surgery, Beijing, China.
    2
    Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.
    3
    Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.
    4
    Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
    5
    Department of Otolaryngology-Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Key Laboratory of Otolaryngology Head and Neck Surgery, Beijing, China. gli@mdanderson.org enthuangzhigang@sohu.com.
    6
    Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
    7
    Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
    8
    Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina.
    9
    Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas. gli@mdanderson.org enthuangzhigang@sohu.com.

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