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Four Gene Polymorphisms as Potential Predictive Biomarkers for Lung Cancer Susceptibility and Therapeutic Response in
Mohammed Ouda Orabiy1, Doaa Hadi Chyad1, Wisam Hindawi Hoidy2
1Ministry of Education, General Directorate of Al-Qadisiyah Education, Al-Diwaniyah City, Iraq.
Background:
Lung cancer remains the leading cause of cancer-related deaths worldwide, with limited genetic data available on Middle Eastern populations. This study investigated four novel genetic variants CYPHER rs7834621, METOX1 rs9284659, DRUGRES2 rs4521739, and TOXMET3 rs8823471 for their association with lung cancer risk and treatment response in Iraqi patients.
Methods:
Between January 2024 and September 2024, we recruited 265 tissue-confirmed lung cancer patients and 310 healthy controls from Al-Diwaniyah Teaching Hospital. DNA was extracted from blood samples and genotyped using tetra-ARMS-PCR. Logistic regression was used to analyze variant-cancer risk associations. Pharmacogenetic analysis included 198 patients receiving trastuzumab, doxorubicin, paclitaxel, and cyclophosphamide chemotherapy, with response measured by RECIST criteria.
Results:
All four genetic variants showed significant associations with lung cancer risk. The CYPHER rs7834621 GG genotype was associated with the highest disease risk (adjusted OR = 2.21, 95% CI: 1.31-3.73, p = 0.003). Allele frequencies were population-specific when compared to other cohorts. Pharmacogenetic analysis revealed treatment response associations, with DRUGRES2 rs4521739 TT genotype demonstrating superior response rates compared to CC genotype (68.4% vs 31.6%, p < 0.001). Haplotype analysis identified specific gene combinations that increased disease susceptibility.
Conclusions:
These novel SNPs are associated with both lung cancer risk and treatment response in Iraqi patients, potentially serving as biomarkers for risk stratification and personalized therapy guidance in this population.
Insights
Novel genetic variants (CYPHER, METOX1, DRUGRES2, TOXMET3) are linked to lung cancer risk and treatment response in Iraqi patients. These findings could guide personalized lung cancer therapies for this population.
Area of Science:
- Genetics
- Oncology
- Pharmacogenomics
Background:
- Lung cancer is a leading cause of cancer mortality globally.
- Limited genetic data exists for Middle Eastern populations regarding lung cancer.
- This study focuses on novel genetic variants in Iraqi patients.
Purpose of the Study:
- Investigate associations of four novel genetic variants (CYPHER rs7834621, METOX1 rs9284659, DRUGRES2 rs4521739, TOXMET3 rs8823471) with lung cancer risk.
- Analyze the impact of these variants on treatment response in Iraqi lung cancer patients.
Main Methods:
- Recruited 265 lung cancer patients and 310 healthy controls.
- Genotyped DNA using tetra-ARMS-PCR and analyzed variant-cancer risk with logistic regression.
- Conducted pharmacogenetic analysis on 198 patients receiving chemotherapy, assessing response via RECIST criteria.
Main Results:
- All four variants showed significant associations with lung cancer risk; CYPHER rs7834621 GG genotype had the highest risk.
- Allele frequencies were population-specific compared to other cohorts.
- DRUGRES2 rs4521739 TT genotype correlated with superior chemotherapy response rates (68.4% vs 31.6%).
Conclusions:
- Novel single nucleotide polymorphisms (SNPs) are associated with lung cancer risk and treatment response in Iraqi patients.
- These SNPs may serve as biomarkers for risk stratification.
- Findings support personalized therapy guidance for lung cancer in this population.
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