Author of

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  OA11 - Thymic and Other Thoracic Tumours: Targeted Therapies, Biomarkers and Neo/Adjuvant Radiotherapy (ID 919)

  • Event: WCLC 2018
  • Type: Oral Abstract Session
  • Track: Thymoma/Other Thoracic Malignancies
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/25/2018, 13:30 - 15:00, Room 205 BD

  • 26089

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    OA11.06 - Two BRM Promoter Polymorphisms Do Not Predict Susceptibility or Prognosis of Thymoma (ID 12745)

    14:25 - 14:35  |  Author(s): Daniel Shepshelovich
    • Abstract
    • Presentation
    • Slides

    Background
    

    Brahma (BRM) is a critical protein subunit in chromatin remodeling, and insertions/deletions at its two polymorphic promotor sites (BRM-741 and BRM-1321) have been reported as susceptibility and/or prognostic markers in lung, head and neck, esophageal, pancreatic, and liver cancers. There is also early evidence of potential association with immune-related diseases such as ulcerative colitis and rheumatoid arthritis. As epigenetic silencing of BRM can be pharmacologically reversed, BRM polymorphisms in cancer might have therapeutic implications. Thymoma is a unique cancer in that it has immunological disease associations. We evaluated whether BRM-741 and BRM-1321 polymorphisms influence overall risk, survival, and time-to-progression of thymoma.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    Thymoma cases and matched healthy controls were recruited in a comprehensive cancer centre. Study participants’ peripheral blood samples were collected and genotyped for BRM promoter polymorphisms. Multivariable logistic regression assessed risk of thymoma in case-control analyses. Association of BRM variants with overall survival (OS) and time-to-progression or recurrence (TTP) was assessed by multivariable Cox regression.

    4c3880bb027f159e801041b1021e88e8 Result
    

    Of 237 cases of histologically diagnosed thymoma and 948 age- and gender-matched healthy controls, thymoma patients had median age of 53 (range: 17-84) years; 121 (51%) were male; 76 (32%) had a history of myasthenia gravis. Median follow-up time was 7 years. 79% of patients were recurrence- and progression-free at 10-year follow-up (95% CI: 74-86%), and 81% of patients were alive at 10 years post-diagnosis (95% CI: 75-87%). Frequency of homozygous variants for either gene was not significantly different between thymoma cases and controls: homozygous BRM-741genotype (OR=1.0; 95%CI:0.6-1.8; P=0.95), homozygous BRM-1321 (OR=0.59; 95%CI:0.3-1.0; P=0.07) or double homozygous variants in both loci (OR=0.69; 95%CI:0.3-1.4; P=0.29). No association between BRM-741/BRM-1321 and OS and TTP was detected (For homozygous BRM-741, OS P=0.74, TTP P=0.93; for homozygous BRM-1321 OS P=0.39, TTP P=0.93). Consistently, there was also no association between double homozygous variants and OS and TTP (Double homozygous, OS P=0.64, TTP P=0.48). Heterozygous variants were also not associated with either risk or outcome.

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    Results of this study do not support use of BRM promoter polymorphisms as susceptibility or prognostic markers for thymoma. Molecular biologic mechanisms of risk and prognosis remain elusive in malignant thymoma.

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