Soy Isoflavone Supplementation Increases Long Interspersed Nucleotide Element-1 (LINE-1) Methylation in Head and Neck Squamous Cell Carcinoma. (4th July 2019)

• Record Type: Journal Article
• Authors: Rozek, Laura S.; Virani, Shama; Bellile, Emily L.; Taylor, Jeremy M. G.; Sartor, Maureen A.; Zarins, Katie R.; Virani, A.; Cote, C.; Worden, Francis P.; Mark, Mark E. Prince; McLean, Scott A.; Duffy, Sonya A.; Yoo, George H.; Saba, Nabil F.; Shin, Dong M.; Kucuk, Omer; Wolf, Gregory T.
• Is Part Of: Nutrition and cancer. Volume 71:Number 5(2019)
• Page Start: 772
• Page End: 780
• Publication Date: 2019-07-04
• Subjects: Cancer -- Periodicals; Nutrition -- Periodicals; Cancer; Nutrition; Periodicals; 616.9940654
• DOI: 10.1080/01635581.2019.1577981
• Languages: English
• ISSNs: 0163-5581

Abstract

Abstract: Aim: Soy isoflavones have been suggested as epigenetic modulating agents with effects that could be important in carcinogenesis. Hypomethylation of LINE-1 has been associated with head and neck squamous cell carcinoma (HNSCC) development from oral premalignant lesions and with poor prognosis. To determine if neoadjuvant soy isoflavone supplementation could modulate LINE-1 methylation in HNSCC, we undertook a clinical trial. Methods: Thirty-nine patients received 2–3 weeks of soy isoflavone supplements (300 mg/day) orally prior to surgery. Methylation of LINE-1, and 6 other genes was measured by pyrosequencing in biopsy, resection, and whole blood (WB) specimens. Changes in methylation were tested using paired t tests and ANOVA. Median follow up was 45 months. Results: LINE-1 methylation increased significantly after soy isoflavone ( P < 0.005). Amount of change correlated positively with days of isoflavone taken ( P = 0.04). Similar changes were not seen in corresponding WB samples. No significant changes in tumor or blood methylation levels were seen in the other candidate genes. Conclusion: This is the first demonstration of in vivo increases in tissue-specific global methylation associated with soy isoflavone intake in patients with HNSCC. Prior associations of LINE-1 hypomethylation with genetic instability, carcinogenesis, and prognosis suggest that soy isoflavones maybe potential chemopreventive agents in HNSCC.