Targeted Gene Sequencing for Head and Neck Cancer Candidate Genes in the Nepal case-control study
- 1Department of Epidemiology, UCLA Fielding School of Public Health
Abstract
Head and Neck cancer (HNC) remains a major global cancer burden, with high incidence and mortality in low- and middle-income countries. Although several genetic variants associated with HNC risk have been identified, cancer predisposition genes in underrepresented populations remain poorly understood. We conducted a hospital-based case-control study at B.P. Koirala Memorial Cancer Hospital in Nepal with 315 HNC cases and 323 controls. Demographic, lifestyle, and clinical data were collected through in-person interviews. Targeted gene sequencing of 493 candidate HNC risk genes were performed, followed by gene- and pathway-based association analyses, and clinical annotation of the identified variants. Consistent with prior findings, HNC incidence increased significantly with alcohol and cigarette use, lower education, and lower socio-economic status. Gene-based analyses identified several genes with suggestive associations prior to multiple-testing adjustment, including HSPG2, KRT6B, SLC4A2, and FREM1. Similarly, no pathways remained statistically significant after adjustment. However, it identified potential biological processes, including extracellular matrix organization, epithelial differentiation, and transcription regulation. Analysis of six cancer predisposition genes (APC, BAP1, BRCA1, BRCA2, RAD51B, and MUTYH) identified pathogenic and likely pathogenic variants with clinical relevance, although no significant enrichment was observed between cases and controls. This study provides the first targeted sequencing analysis combined with epidemiological data for HNC in the Nepalese population, an underrepresented high-risk group. While no significant genetic associations were identified, clinically relevant rare variants were detected. Larger studies in South Asian populations are needed to improve the detection of rare variants and to inform risk assessment.
Related
- Integrating bulk and single-cell RNA sequencing to identify mitochondrial quality control-related key genes in rheumatoid arthritis
- Targeted Sequencing-Based Re-Evaluation of Candidate Immunogenetic Variants for Biologic Treatment Response and Difficult-to-Treat Rheumatoid Arthritis
- Single‑cell and bulk RNA sequencing identifies T cell marker genes to predict the prognosis of ovarian cancer
- Identification of NUDT6 and LINGO1 as candidate genes for nCRT-associated signatures to neoadjuvant chemoradiotherapy in rectal cancer patients
- Metabolic syndrome and colorectal cancer share GPAT3 and PLAU as candidate genes: Mendelian randomisation, machine learning, single-cell knockout and docking
BibTeX
@misc{thapa2026targeted,
title = {{Targeted Gene Sequencing for Head and Neck Cancer Candidate Genes in the Nepal case-control study}},
author = {I. Thapa and C.-P. E. Chang and A. K. Snow and J. Rosenthal and R. Bell and A. Wood and B. Siwakoti and A. Sapkota and D. K. Gautam and S. V. Tavtigian and B.-J. Feng and M. Hashibe},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.27.26366653},
url = {https://www.medrxiv.org/content/10.64898/2026.10.27.26366653v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Targeted Gene Sequencing for Head and Neck Cancer Candidate Genes in the Nepal case-control study
AU - I. Thapa
AU - C.-P. E. Chang
AU - A. K. Snow
AU - J. Rosenthal
AU - R. Bell
AU - A. Wood
AU - B. Siwakoti
AU - A. Sapkota
AU - D. K. Gautam
AU - S. V. Tavtigian
AU - B.-J. Feng
AU - M. Hashibe
PY - 2026
DA - 2026/10/27
PB - medRxiv
DO - 10.64898/2026.10.27.26366653
UR - https://www.medrxiv.org/content/10.64898/2026.10.27.26366653v1
AB - Head and Neck cancer (HNC) remains a major global cancer burden, with high incidence and mortality in low- and middle-income countries. Although several genetic variants associated with HNC risk have been identified, cancer predisposition genes in underrepresented populations remain poorly understood. We conducted a hospital-based case-control study at B.P. Koirala Memorial Cancer Hospital in Nepal with 315 HNC cases and 323 controls. Demographic, lifestyle, and clinical data were collected through in-person interviews. Targeted gene sequencing of 493 candidate HNC risk genes were performed, followed by gene- and pathway-based association analyses, and clinical annotation of the identified variants. Consistent with prior findings, HNC incidence increased significantly with alcohol and cigarette use, lower education, and lower socio-economic status. Gene-based analyses identified several genes with suggestive associations prior to multiple-testing adjustment, including HSPG2, KRT6B, SLC4A2, and FREM1. Similarly, no pathways remained statistically significant after adjustment. However, it identified potential biological processes, including extracellular matrix organization, epithelial differentiation, and transcription regulation. Analysis of six cancer predisposition genes (APC, BAP1, BRCA1, BRCA2, RAD51B, and MUTYH) identified pathogenic and likely pathogenic variants with clinical relevance, although no significant enrichment was observed between cases and controls. This study provides the first targeted sequencing analysis combined with epidemiological data for HNC in the Nepalese population, an underrepresented high-risk group. While no significant genetic associations were identified, clinically relevant rare variants were detected. Larger studies in South Asian populations are needed to improve the detection of rare variants and to inform risk assessment.
ER -