PMID- 34952175 OWN - NLM STAT- MEDLINE DCOM- 20220210 LR - 20221207 IS - 1879-0038 (Electronic) IS - 0378-1119 (Linking) VI - 813 DP - 2022 Mar 1 TI - The impact of prehistoric human dispersals on the presence of tobacco-related oral cancer in Northeast India. PG - 146098 LID - S0378-1119(21)00693-4 [pii] LID - 10.1016/j.gene.2021.146098 [doi] AB - BACKGROUND: Northeast (NE) India is a subject of debate for predicting its involvement in prehistoric anatomically modern human (AMH) dispersal. The unique lifestyle and genetic characteristics of native ethnic groups in this region are believed to be responsible for their susceptibility to tobacco-related oral cancer (TrOC). The present study assessed mitochondrial macro-haplogroup (mHG) diversity and TrOC susceptibility autosomal loci to evaluate the impact of prehistoric AMH dispersal on the present day's high TrOC prevalence in major NE Indian ethnics. METHODS: We considered 175 unrelated individuals from 35 ethnic groups and previously published 374 sequences for sequencing-based assessment of mtDNA-based marker by subsequent analyses like haplogroup diversity, phylogenetic, genetic structure by AMOVA, and MDS, descriptive statistics of demographic parameters, and migration analysis. Besides, we selected prolonged tobacco-chewing 124 case-control individuals from similar ethnic backgrounds for genotyping 115 autosomal loci in Sequenom iPLEX MassARRAY platform and mined 1000genome data (n = 398) for consequent global admixture and ancestry-specific allele frequencies-based analyses. RESULTS: Our mtDNA-based findings suggested that NE populations were distinct from other Indian populations, owing to the first wave of migration from ancient southern China ( approximately 54kya) and two successive spatial expansion events at approximately 45kya and approximately 43kya. Consequently, it probably acted as another source for prehistoric AMH dispersal in N/NE Asia. Besides, the second wave of back-migration from SE Asia ( approximately 40kya) probably replaced the mitochondrial footprints of survivors from the first migrants and introduced the TrOC susceptibility traits in this region. Afterward, the autosomal marker-based observations on the transition of the disease-associated admixture component 'K6' from SE Asia reconfirmed these results. Moreover, we also observed that the mitochondrial mHG 'R' is significantly associated with the risk of TrOC (OR > 9.5) in NE India. Furthermore, the possible onset of the phenotypic expression of those traits was predicted at approximately 4kya, thus, contributing to present-day's TrOC prevalence. CONCLUSIONS: This study reflects its uniqueness by revealing an updated AMH dispersal route for the peopling in and out of NE India, which probably introduced the disease-causing traits in the ancestral NE Indian population. Those traits were then imprinted in their genome to get transferred through their respective generations, forming the present-day's TrOC-prevalent NE Indian population. CI - Copyright (c) 2022 Elsevier B.V. All rights reserved. FAU - Kundu, Sharbadeb AU - Kundu S AD - Genome Science, School of Interdisciplinary Studies, University of Kalyani, Nadia 741235, West Bengal, India; Department of Biotechnology, Assam University, Silchar 788011, Assam, India. FAU - Dhar, Bishal AU - Dhar B AD - S. N. Bose Innovation Centre, University of Kalyani, Nadia 741235, West Bengal, India. FAU - Das, Raima AU - Das R AD - Department of Biotechnology, Assam University, Silchar 788011, Assam, India. FAU - Laskar, Shaheen AU - Laskar S AD - Department of Biotechnology, Assam University, Silchar 788011, Assam, India. FAU - Singh, Seram Anil AU - Singh SA AD - Institute of Bioresources and Sustainable Development, Takyelpat, Imphal 795001, Manipur, India. FAU - Kapfo, Wetetsho AU - Kapfo W AD - Healthcare Laboratory and Research Centre, Naga Hospital Authority, Kohima 797001, Nagaland, India. FAU - Paul, Rajesh AU - Paul R AD - Department of Animal Genetics and Breeding, College of Veterinary Science and Animal Husbandry, Tripura 799008, India. FAU - Ramshankar, Vijayalakshmi AU - Ramshankar V AD - Department of Preventive Oncology (Research), Cancer Institute (W.I.A.), Chennai 600020, Tamil Nadu, India. FAU - Choudhury, Yashmin AU - Choudhury Y AD - Department of Biotechnology, Assam University, Silchar 788011, Assam, India. FAU - Ghosh, Sankar Kumar AU - Ghosh SK AD - Department of Biotechnology, Assam University, Silchar 788011, Assam, India. Electronic address: drsankarghosh@gmail.com. LA - eng PT - Journal Article DEP - 20211222 PL - Netherlands TA - Gene JT - Gene JID - 7706761 RN - 0 (DNA, Mitochondrial) SB - IM MH - Adult MH - Asian People/genetics MH - Case-Control Studies MH - DNA, Mitochondrial/genetics MH - Ethnicity/genetics MH - Female MH - Gene Frequency MH - Genetic Predisposition to Disease MH - Genetic Variation MH - Genetics, Population/methods MH - Haplotypes MH - Human Migration MH - Humans MH - India/epidemiology MH - Male MH - Middle Aged MH - Mouth Neoplasms/blood/*epidemiology/etiology/genetics MH - Phylogeny MH - Tobacco Smoking MH - Tobacco Use/blood/*epidemiology/genetics MH - Young Adult OTO - NOTNLM OT - AMOVA OT - Anatomically modern human dispersal OT - Ancestry-specific allele frequency OT - Disease-associated admixture component OT - Global admixture analysis OT - Migration analysis OT - Mitochondrial macro-haplogroup diversity OT - Multidimensional scaling OT - Northeast India OT - Oral cancer susceptibility autosomal loci OT - Prehistoric migration route OT - Prolonged tobacco-chewers OT - Tobacco-related oral cancer OT - mtDNA-based marker EDAT- 2021/12/25 06:00 MHDA- 2022/02/11 06:00 CRDT- 2021/12/24 20:11 PHST- 2021/06/28 00:00 [received] PHST- 2021/10/20 00:00 [revised] PHST- 2021/11/16 00:00 [accepted] PHST- 2021/12/25 06:00 [pubmed] PHST- 2022/02/11 06:00 [medline] PHST- 2021/12/24 20:11 [entrez] AID - S0378-1119(21)00693-4 [pii] AID - 10.1016/j.gene.2021.146098 [doi] PST - ppublish SO - Gene. 2022 Mar 1;813:146098. doi: 10.1016/j.gene.2021.146098. Epub 2021 Dec 22.