مقالات پذیرفته شده در نهمین کنگره بین المللی زیست پزشکی
Genetic Insights into MLH1 rs1800734 and Colorectal Cancer: Evidence from the Largest Iranian Cohort with Meta-Analysis
Genetic Insights into MLH1 rs1800734 and Colorectal Cancer: Evidence from the Largest Iranian Cohort with Meta-Analysis
Monir Sadat Haerian,1,*Batoul Sadat Haerian,2Saadat Molanaei,3Farid Kosari,4Shahram Sabeti,5Farahnaz Bidari-zerehpoosh,6
1. Food and Drug Control Reference Lab Center, Ministry of Health and Medical Education (FDCRLC) 4. Department of Pathology, Sina Hospital, Tehran University of Medical Sciences 5. Department of Pathology, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences 6. Department of Pathology, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences
Introduction: Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer-related deaths. Its incidence varies across different populations, influenced in part by genetic factors, highlighting the need to identify genetic variants associated with CRC susceptibility. This study investigates whether the MLH1 rs1800734 G > A polymorphism contributes to CRC risk in an Iranian population, representing the Middle East. A total of 2,590 individuals, including 1,038 CRC patients, were recruited from four hospitals in Tehran. Genotyping for MLH1 rs1800734 was conducted using TaqMan® real-time PCR. Findings indicate a significant association between the AA genotype and an increased risk of CRC (OR = 1.49, 95% CI = 1.16–1.92, p = 0.002). The risk was notably higher among individuals aged 50 and older and in females carrying the AA genotype (OR = 1.66, 95% CI: 1.12–2.47, p = 0.012 and OR = 1.54, 95% CI: 1.16–2.04, p = 0.003, respectively). A meta-analysis incorporating 14 studies along with the Iranian cohort (N = 40,051) did not identify significant associations after applying the Bonferroni correction for multiple comparisons. These findings emphasize the importance of considering age and gender in genetic risk assessments for CRC. As one of the largest cohort studies from the Middle East, this study suggests that the MLH1 rs1800734 AA genotype may contribute to CRC susceptibility, particularly in older individuals and women. Further large-scale studies are necessary to refine risk assessments for AA genotype carriers in CRC.
Keywords: colorectal cancer; MLH1 rs1800734 polymorphism; susceptibility variant; meta-analysis
Methods: A multicenter case-control study was conducted in Tehran hospitals, including CRC patients and matched controls. Demographic and clinical data were collected, and DNA was extracted from FFPE tissues and blood. Genotyping of MLH1 rs1800734 G > A was performed using TaqMan® real-time PCR, with 5% of samples validated by direct sequencing. Logistic regression adjusted for age and gender was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), with Bonferroni correction applied. A systematic review and meta-analysis was performed following PRISMA guidelines using five databases, including studies up to January 2025.
Results: Findings indicate a significant association between the AA genotype and an increased risk of CRC (OR = 1.49, 95% CI = 1.16–1.92, p = 0.002). The risk was notably higher among individuals aged 50 and older and in females carrying the AA genotype (OR = 1.66, 95% CI: 1.12–2.47, p = 0.012 and OR = 1.54, 95% CI: 1.16–2.04, p = 0.003, respectively). A meta-analysis incorporating 14 studies along with the Iranian cohort (N = 40,051) did not identify significant associations after applying the Bonferroni correction for multiple comparisons.
Conclusion: These findings emphasize the importance of considering age and gender in genetic risk assessments for CRC. As one of the largest cohort studies from the Middle East, this study suggests that the MLH1 rs1800734 AA genotype may contribute to CRC susceptibility, particularly in older individuals and women.