Kapil Bandil1, Pallavi Singhal1, Upma Sharma1, Showket Hussain1, Surojit Basu2, Aditya Parashari3, Veena Singh4, Ashok Sehgal5, Animesh Shivam6, Puneet Ahuja6, Mausumi Bharadwaj7, Basu Dev Banerjee8, Ravi Mehrotra9. 1. Division of Molecular Genetics and Biochemistry, Institute of Cytology and Preventive Oncology (ICMR), I-7, Sector-39, Noida, 20130, India. 2. Barasat Cancer Hospital, Kolkata, India. 3. Division of Molecular Immunology, Institute of Cytology and Preventive Oncology (ICMR), I-7, Sector-39, Noida, India. 4. Division of Clinical Oncology, Institute of Cytology and Preventive Oncology (ICMR), I-7, Sector-39, Noida, India. 5. Division of Epidemiology and Biostatistics, Institute of Cytology and Preventive Oncology (ICMR), I-7, Sector-39, Noida, India. 6. Department of Oral Pathology, Institute of Technology and Science, Greater Noida, India. 7. Division of Molecular Genetics and Biochemistry, Institute of Cytology and Preventive Oncology (ICMR), I-7, Sector-39, Noida, 20130, India. bharadwajm@icmr.org.in. 8. Department of Biochemistry, University College of Medical Sciences, University of Delhi Dilshad Graden, Delhi-65, India. 9. Division of Cytopathology, Institute of Cytology and Preventive Oncology (ICMR), I-7, Sector-39, Noida, India.
Abstract
BACKGROUND AND OBJECTIVES: To investigate a potential association between single-nucleotide polymorphisms (SNPs) and haplotypes at the TNFA-LTA locus and the development of oral cancer in an Indian population. MATERIALS AND METHODS: In this study, 150 oral precancer/cancer samples (50 precancer and 100 cancer), along with an equal number of control samples, were genotyped. Six SNPs at the TNF-LTA locus (i.e., -238G/A, -308G/A, -857C/T, -863C/A, -1031T/C, and +252A/G) were analyzed by use of a polymerase chain reaction-restriction fragment length polymorphism method, the assay was validated by sequencing 10 % of samples. RESULTS: The allelic frequencies of TNFA and LTA SNPs were found to be significantly associated with the risk of oral cancer and precancerous lesions in comparison with controls (P < 0.0003). Further haplotypic analysis showed that two haplotypes (ATCTGG and ACACGG) served as risk haplotypes for oral cancer. These haplotypes were also found to be significantly and positively associated with lifestyle habits (tobacco chewing P = 0.04, odds ratio [OR] 3.4) and socioeconomic status (P = 0.01, OR 3.4). We noticed an increased percentage of risk haplotypes correlating with the aggressiveness of oral cancer. The percentages of risk haplotypes were found to be threefold higher in precancer and fourfold higher in advanced stages of oral cancer in comparison with controls. CONCLUSION: Five SNPs at the TNF-LTA locus (i.e., -308G>A, -857C>T, -863C>A, -1031T>C, and +252A>G) were found to be associated with the development of oral cancer. Two haplotypes (ATCTGG and ACACGG) emerged as major risk haplotypes for oral carcinoma progression and were also found to be associated with lifestyle factors and clinical aggressiveness. These findings make the TNF-LTA locus a suitable candidate for a future biomarker, which may be used either for early detection or for helping to improve treatment efficacy and effectiveness.
BACKGROUND AND OBJECTIVES: To investigate a potential association between single-nucleotide polymorphisms (SNPs) and haplotypes at the TNFA-LTA locus and the development of oral cancer in an Indian population. MATERIALS AND METHODS: In this study, 150 oral precancer/cancer samples (50 precancer and 100 cancer), along with an equal number of control samples, were genotyped. Six SNPs at the TNF-LTA locus (i.e., -238G/A, -308G/A, -857C/T, -863C/A, -1031T/C, and +252A/G) were analyzed by use of a polymerase chain reaction-restriction fragment length polymorphism method, the assay was validated by sequencing 10 % of samples. RESULTS: The allelic frequencies of TNFA and LTA SNPs were found to be significantly associated with the risk of oral cancer and precancerous lesions in comparison with controls (P < 0.0003). Further haplotypic analysis showed that two haplotypes (ATCTGG and ACACGG) served as risk haplotypes for oral cancer. These haplotypes were also found to be significantly and positively associated with lifestyle habits (tobacco chewing P = 0.04, odds ratio [OR] 3.4) and socioeconomic status (P = 0.01, OR 3.4). We noticed an increased percentage of risk haplotypes correlating with the aggressiveness of oral cancer. The percentages of risk haplotypes were found to be threefold higher in precancer and fourfold higher in advanced stages of oral cancer in comparison with controls. CONCLUSION: Five SNPs at the TNF-LTA locus (i.e., -308G>A, -857C>T, -863C>A, -1031T>C, and +252A>G) were found to be associated with the development of oral cancer. Two haplotypes (ATCTGG and ACACGG) emerged as major risk haplotypes for oral carcinoma progression and were also found to be associated with lifestyle factors and clinical aggressiveness. These findings make the TNF-LTA locus a suitable candidate for a future biomarker, which may be used either for early detection or for helping to improve treatment efficacy and effectiveness.
Authors: Christina Fitzmaurice; Daniel Dicker; Amanda Pain; Hannah Hamavid; Maziar Moradi-Lakeh; Michael F MacIntyre; Christine Allen; Gillian Hansen; Rachel Woodbrook; Charles Wolfe; Randah R Hamadeh; Ami Moore; Andrea Werdecker; Bradford D Gessner; Braden Te Ao; Brian McMahon; Chante Karimkhani; Chuanhua Yu; Graham S Cooke; David C Schwebel; David O Carpenter; David M Pereira; Denis Nash; Dhruv S Kazi; Diego De Leo; Dietrich Plass; Kingsley N Ukwaja; George D Thurston; Kim Yun Jin; Edgar P Simard; Edward Mills; Eun-Kee Park; Ferrán Catalá-López; Gabrielle deVeber; Carolyn Gotay; Gulfaraz Khan; H Dean Hosgood; Itamar S Santos; Janet L Leasher; Jasvinder Singh; James Leigh; Jost B Jonas; Jost Jonas; Juan Sanabria; Justin Beardsley; Kathryn H Jacobsen; Ken Takahashi; Richard C Franklin; Luca Ronfani; Marcella Montico; Luigi Naldi; Marcello Tonelli; Johanna Geleijnse; Max Petzold; Mark G Shrime; Mustafa Younis; Naohiro Yonemoto; Nicholas Breitborde; Paul Yip; Farshad Pourmalek; Paulo A Lotufo; Alireza Esteghamati; Graeme J Hankey; Raghib Ali; Raimundas Lunevicius; Reza Malekzadeh; Robert Dellavalle; Robert Weintraub; Robyn Lucas; Roderick Hay; David Rojas-Rueda; Ronny Westerman; Sadaf G Sepanlou; Sandra Nolte; Scott Patten; Scott Weichenthal; Semaw Ferede Abera; Seyed-Mohammad Fereshtehnejad; Ivy Shiue; Tim Driscoll; Tommi Vasankari; Ubai Alsharif; Vafa Rahimi-Movaghar; Vasiliy V Vlassov; W S Marcenes; Wubegzier Mekonnen; Yohannes Adama Melaku; Yuichiro Yano; Al Artaman; Ismael Campos; Jennifer MacLachlan; Ulrich Mueller; Daniel Kim; Matias Trillini; Babak Eshrati; Hywel C Williams; Kenji Shibuya; Rakhi Dandona; Kinnari Murthy; Benjamin Cowie; Azmeraw T Amare; Carl Abelardo Antonio; Carlos Castañeda-Orjuela; Coen H van Gool; Francesco Violante; In-Hwan Oh; Kedede Deribe; Kjetil Soreide; Luke Knibbs; Maia Kereselidze; Mark Green; Rosario Cardenas; Nobhojit Roy; Taavi Tillmann; Taavi Tillman; Yongmei Li; Hans Krueger; Lorenzo Monasta; Subhojit Dey; Sara Sheikhbahaei; Nima Hafezi-Nejad; G Anil Kumar; Chandrashekhar T Sreeramareddy; Lalit Dandona; Haidong Wang; Stein Emil Vollset; Ali Mokdad; Joshua A Salomon; Rafael Lozano; Theo Vos; Mohammad Forouzanfar; Alan Lopez; Christopher Murray; Mohsen Naghavi Journal: JAMA Oncol Date: 2015-07 Impact factor: 31.777
Authors: A M Uglialoro; D Turbay; P A Pesavento; J C Delgado; F E McKenzie; J G Gribben; D Hartl; E J Yunis; A E Goldfeld Journal: Tissue Antigens Date: 1998-10
Authors: Stefano Volpato; Marco Pahor; Luigi Ferrucci; Eleanor M Simonsick; Jack M Guralnik; Stephen B Kritchevsky; Renato Fellin; Tamara B Harris Journal: Circulation Date: 2004-02-10 Impact factor: 29.690
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