Abstract 3114: Soy isoflavones modulate global methylation in head and neck squamous cell carcinoma (HNSCC)
Bibliographic record
Abstract
Abstract Soy intake has been associated with improved survival in HNSCC and soy isoflavones have been suggested as potential chemopreventive agents with a favorable therapeutic index and safety profile. Multiple in vivo and in vitro anti-cancer effects have been postulated including modulation of gene methylation. To determine if high dose soy isoflavone treatment changes methylation of genes associated with cancer outcomes, we measured genomic and gene-specific methylation in tumor tissue collected as a part of a multi-institutional neoadjuvant soy isoflavone clinical trial in HNSCC patients undergoing definitive surgical management. Methods: Thirty-nine patients participated in this clinical trial. Patients were scheduled to receive 2 weeks (range 7-39 days, median = 15.2) of soy isoflavone supplements (300 mg/day G-2535; DCP, NCI, NIH) orally prior to surgery. Levels of methylation of LINE-1 (global methylation), and 6 other candidate genes previously associated with HNSCC (p16, DCC, NDN, CD1a, CCNA1 and Gadd45α) were measured by pyrosequencing in biopsy, resection and whole blood specimens. Twelve patients were stage I/II, 27 were stage III/IV. Thirty one patients had cancer of the oral cavity, 4 had larynx and 4 had oropharynx cancer. Mean age of the patients was 60.1 (sd = 12.5). Changes in methylation were tested using paired t-tests and clinical associations explored using ANOVA. Results: LINE-1 methylation increased significantly (mean increase 4.9%; range -34.8% to +20.9%) in tumor specimens after soy isoflavone (p<0.005). Amount of change correlated positively with days of isoflavone taken (p = .009). Increases in LINE-1 methylation in tumor were greatest in patients with normal BMI (p<0.03). Similar changes for LINE-1 were not seen in corresponding whole blood samples. No other significant changes in tumor or blood methylation levels were seen in the other candidate genes. Baseline tumor methylation and change in methylation were also studied with respect to nutrition (BMI), drinking, tumor site, tumor stage, nodal status and prior treatment. Baseline CD1a methylation was lowest in current smokers (p<0.04) and increases in CD1a after soy intake were associated with increasing pack years (p<0.02). CD1a methylation was also higher in patients with T1,2 tumors (p<0.03). Pretreatment NDN methylation was lower (p<.008) and LINE-1 higher (p<0.0001) in oral cavity cancer compared to oropharynx or larynx cancers. Toxicity from soy isoflavones was negligible and patient compliance was excellent. Conclusions: This is the first demonstration of significant increases in tissue-specific global methylation associated with soy isoflavone intake, indicating increased genomic stability. The association of hypomethylation of LINE-1 with genetic instability, carcinogenesis and poor treatment outcomes suggests that soy isoflavones should be studied further as a potential chemopreventive agent in HNSCC. Citation Format: Laura Rozek, Shama Virani, Emily Bellile, Jeremy Taylor, Maureen Sartor, Alisha Virani, Katie Rentschler, Claire Cote, Francis Worden, Lisa Peterson, Douglas Chepeha, Mark Prince, Scott McLean, George Yoo, Neil F. Saba, Dong M. Shin, Omer Kucuk, Gregory T. Wolf. Soy isoflavones modulate global methylation in head and neck squamous cell carcinoma (HNSCC). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3114.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".