Abstract B024: Causal Association between Wnt/β-catenin Gene expression with Cervical Cancer Risk: Two Sample Mendelian Randomization (MR)

Abstract Background: Increasing evidence indicates that Wnt/β-catenin signaling, one of the best-characterized cancer drivers, promotes cancer progression by regulating the tumor-immune cycle. This study aims to test this hypothesis using Mendelian Randomization (MR), which can infer causality free from confounding factors. Methods: We utilized the Icelandic deCODE Genetics dataset (deCODE), published by Ferkingstad et al. (2021), which analyzes genetic variations, plasma proteins, and diseases in a cohort of 35,559 Icelandic individuals. Additionally, we used the Biobank Japan (BBJ) dataset, a large-scale biobank comprising genetic and biomarker information from approximately 200,000 Japanese individuals. Genetic variations related to the protein quantitative trait loci (pQTL) for Wnt/β-catenin genes (specifically WNT10A) were identified in the deCODE dataset. Corresponding SNPs associated with cervical cancer risk were identified in the BBJ dataset. We examined the pQTL-related single nucleotide polymorphisms (SNPs) of Wnt/β-catenin genes. Two-sample MR was performed to infer causality between Wnt/β-catenin pQTL expression levels and cervical cancer risk using the SNPs identified in the BBJ biobank. Results Before removing outliers, the analysis included 9 SNPs related to the pQTL expression of WNT10A. Using inverse variance weighting, the odds ratio (OR) was calculated as 1.19 (0.71-2.00, 95% confidence interval, p-value: 0.5044), indicating no statistically significant causality. After removing duplicated SNPs and conducting Linkage Disequilibrium (LD) clumping, 7 SNPs were included in the final analysis. The effect of WNT10A on cervical cancer was recalculated using inverse variance weighting, yielding an OR of 1.21 (0.79-1.84, 95% confidence interval, p-value: 0.3767), still indicating no statistically significant causality. Conclusions This study highlights the application of MR, which is robust against confounding variables, to explore the causal association between Wnt/β-catenin pQTL expression and cervical cancer risk. While our results do not support a significant causal relationship, the use of MR provides valuable insights and has public health implications for discovering new drug targets or biomarkers for prevention or treatment. Citation Format: Yongho Jee, Woong Ju. Causal Association between Wnt/β-catenin Gene expression with Cervical Cancer Risk: Two Sample Mendelian Randomization (MR) [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr B024.