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

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.
Nutrition and cancer 2019 v.71 no.5 pp. 772-780
analysis of variance, biopsy, blood, carcinogenesis, clinical trials, epigenetics, genes, head and neck neoplasms, isoflavones, methylation, patients, prognosis, resection, sequence analysis, squamous cell carcinoma
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.