A retrospective Case-Control study investigating the association of XPC Lys939Gln (rs2228001), XPD Lys751Gln (rs13181), and TP53 Arg72Pro (rs1042522) with papillary thyroid carcinoma susceptibility in the Bangladeshi population.

Nowshin Jahan Bristy, Md Ariful Islam, Al-Rownoka Noor, M M Towhidul Islam, Yearul Kabir

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Article in Molecular biology reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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Nowshin Jahan BristyDepartment of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, Bangladesh.

Md Ariful IslamDepartment of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, Bangladesh.

Al-Rownoka NoorDepartment of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, Bangladesh.

M M Towhidul IslamDepartment of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, Bangladesh.

Yearul KabirDepartment of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, Bangladesh. ykabir@du.ac.bd.

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Abstract

backgroundPapillary thyroid carcinoma (PTC) is the most common thyroid malignancy, particularly among females. Polymorphisms in DNA repair and tumor suppressor genes such as XPC, XPD, and TP53 may influence cancer susceptibility. This study investigated the association of XPC Lys939Gln, XPD Lys751Gln, and TP53 Arg72Pro variants and PTC risk in a Bangladeshi population, supported by in-silico analyses.

methodsA retrospective case-control study was conducted involving 166 PTC patients and 180 controls. Genotyping was performed using PCR-RFLP and allele-specific multiplex PCR. Logistic regression assessed associations, with subgroup analyses stratified by gender, smoking, and family history. Functional, structural, RNA, splicing, and regulatory effects of each variant were predicted using multiple bioinformatics tools. Pearson's correlation evaluated genotype co-occurrence.

resultsMutant genotypes of all three genes were significantly more frequent in cases. XPD Gln/Gln and TP53 Arg/Pro variants conferred the highest risk. Associations were stronger in females, non-smokers, and individuals with a family history of cancer. Combined genotype analysis suggested synergistic effects. In silico predictions flagged TP53 as most functionally impactful. Structural modeling revealed minimal protein-level disruptions; however, mRNA-level analysis showed reduced transcript stability and increased conformational variability for XPD and TP53. Splicing predicted altered motifs and cryptic site activation for XPD. RegulomeDB suggested strong regulatory potential for XPC. Pearson's correlation revealed mutual exclusivity between XPC and XPD in cases.

conclusionXPC, XPD, and TP53 variants are significantly associated with PTC risk in Bangladeshi population. Combined genetic and bioinformatics evidence supports their potential as biomarkers for risk stratification, warranting larger functional studies.

Indexed as

DNA-Binding ProteinsThyroid Cancer, PapillaryThyroid NeoplasmsTumor Suppressor Protein p53Xeroderma Pigmentosum Group D ProteinAdultBangladeshCase-Control StudiesFemaleGenetic Predisposition to DiseaseGenotypeHumansMaleMiddle AgedPolymorphism, Single NucleotideRetrospective StudiesDNA-Binding ProteinsERCC2 protein, humanTP53 protein, humanTumor Suppressor Protein p53Xeroderma Pigmentosum Group D ProteinXPC protein, humanBangladeshi populationGenetic polymorphismPapillary thyroid carcinomaTP53 geneXPC geneXPD gene

Identifiers

PMID41307639

DOI10.1093/bib/bbx109

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