SynthesisEBioMedicine2025
A genome-wide association study of buccal mucosa cancer in India and multi-ancestry meta-analysis discovers risk loci and gene-environment interactions.
Synthesis in EBioMedicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Integrated Clinical, Histopathological, and Inflammatory Parameters for Predicting Malignant Transformation in High-Risk Oral Potentially Malignant Disorders: A Prospective Study.Head and neck pathology · 2026Article
- Population-specific genomic risk markers for oral and maxillofacial malignancies in a high tobacco-exposure cohort from Eastern Uttar Pradesh, India.Bioinformation · 2026Article
- Impact ofOncology research · 2026Article
- Methods for modeling gene-environment interplay using polygenic risk scores.Statistical applications in genetics and molecular biology · 2026Review
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18 authors.
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Abstract
backgroundGenome-wide association studies (GWASs) of oral cancers (OC) to date have focused predominantly on European Ancestry (EA) populations. India faces an excess burden of OC, but the most common is the buccal mucosa cancer (BMC), which is relatively rare in EA populations.
methodsWe conducted a GWAS comprising 2160 BMC cases and 2325 controls from different geographical locations in India. We additionally conducted a GWAS of 397 BMC cases and 439 controls from Taiwan and performed multi-ancestry GWAS meta-analysis of OC on 5255 cases and 8748 controls across EA, Indian and Taiwanese populations.
findingsSingle SNP analysis of the Indian GWAS discovered a risk locus at 6q27 conferring susceptibility specifically to BMC and identified multiple independent association signals within known OC loci 5p15.33 and 6p21.32 (HLA region). Further, gene-level analysis of multi-ancestry GWAS identified the tumour suppressor gene NOTCH1 as an OC locus. Using data from the Indian BMC GWAS, we further identified statistically significant evidence of multiplicative interactions (P-value = 0.031 likelihood-ratio test (LRT)) between polygenic risk of BMC and tobacco chewing habit, indicating stronger relative-risk associated with genetic predisposition for non-users compared to chewers.
interpretationOur study provides insights into the aetiologies of BMC in India, highlighting both its similarities and differences with other types of oral cavity cancers, as well as the interactions between polygenic risk and tobacco chewing.
fundingDepartment of Health Research, New Delhi-Grant No. ICMR/EU/13/2012/NCD-III. Intramural Research Program, US National Cancer Institute, National Institutes of Health.
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