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p16 hypermethylation: A biomarker for increased esophageal cancer susceptibility in high incidence region of North East India

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Tumor Biology

Abstract

Esophageal cancer is one of the most common cancers in North East India. The molecular mechanisms of esophageal cancer susceptibility in North East India have not been fully understood. There is a need for identification of biomarkers to identify people at risk of esophageal cancer. p16 is an essential G1 cell cycle regulatory gene whose loss of function is associated with carcinogenesis. Therefore, we conducted this study to determine the prevalence of p16 gene methylation in patients with esophageal cancer to assess the feasibility of using gene methylation as a biomarker. A total of 100 newly diagnosed esophageal cancer cases along with equal number of age, sex, and ethnicity-matched controls were included in this study. Methylation-specific PCR was used to determine the p16 methylation status. Aberrant promoter methylation of the p16 gene was detected in 81 of 100 (81 %) esophageal cancer cases. Hypermethylation of p16 gene was found to be influenced by lifestyle factors. Betel quid and tobacco chewing habit synergistically with p16 methylation elevated the risk for esophageal cancer development (adjusted odds ratio (OR) = 6.88, 95 % confidence interval (CI) = 1.64–28.81, p = 0.003 for betel quid chewing and adjusted OR = 7.02, 95 % CI = 1.87–26.38, p = 0.001 for tobacco chewing). Further, intake of green leafy vegetables and fruits lowered the risk of esophageal cancer (adjusted OR = 0.16, 95 % CI = 0.04–0.58, p = 0.05 for green leafy vegetables and adjusted OR = 0.15, 95 % CI = 0.04–0.64, p = 0.01 for fruits). Thus, p16 hypermethylation may aid as a biomarker in identifying habitués at greater risk for esophageal cancer susceptibility in high incidence region of North East India.

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Acknowledgments

This work was supported by the Indian Council of Medical Research (ICMR), Department of Health Research and Government of India under the extramural funding of Northeast Initiative. We would like to thank Dr. Nirmal Sahewala (Consultant Radiologist, Obsteristics and Gynecology) and Dr. Bimal Kumar Jalan (Chief Endoscopist), Aditya Hospital, Dibrugarh, Assam, India, for their support during sample collection. We would also like to thank the staff of Radiology Department, Assam Medical College and Hospital, Dibrugarh, Assam, India.

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  1. Regional Medical Research Centre, N.E. Region (ICMR), Dibrugarh, 786001, Post Box-105, Assam, India

    Mandakini Das, Bhaskar Jyoti Saikia, Santanu Kumar Sharma, Gaganpreet Singh Sekhon, Jagadish Mahanta & Rup Kumar Phukan

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  1. Mandakini Das
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Correspondence to Rup Kumar Phukan.

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Das, M., Saikia, B.J., Sharma, S.K. et al. p16 hypermethylation: A biomarker for increased esophageal cancer susceptibility in high incidence region of North East India. Tumor Biol. 36, 1627–1642 (2015). https://doi.org/10.1007/s13277-014-2762-7

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