Exposing Shared Connections: Genetic Correlations between Esophageal Cancer and Lung Cancer

Abstract Background Lung carcinoma and esophageal carcinoma stand as prevailing malignancies, exhibiting an ascending trajectory in global incidence and mortality rates. Notwithstanding the discernment of particular environmental and behavioral determinants entwined with the evolution of these neoplasms, the enigma of genetic contributions to their progression persists. The present inquiry aspires to scrutinize the intricate genetic affinities underscoring lung carcinoma and esophageal carcinoma, thereby delving into the intertwining comorbidity of these maladies. Methods Employing the linkage disequilibrium score regression (LDSC) framework, we dissected the genetic congruity uniting esophageal carcinoma and lung carcinoma. Subsequently, we harnessed a medley of methodologies, encompassing pleiotropic analysis under the composite null hypothesis (PLACO), multi-marker analysis of genomic annotation (MAGMA), cis-expression quantitative trait loci (eQTL) analysis, and a panoramic cancer appraisal, to unearth pleiotropic loci and genes. Culminating in a bidirectional Mendelian randomization (MR) paradigm, we gauged the causal interplay between these malignancies. Results Inceptive findings divulged a conspicuous genetic correlation between esophageal carcinoma and lung carcinoma via the LDSC methodology. Subsequent endeavors unearthed shared gene loci – namely PGBD1, ZNF323, and WNK1 – through the PLACO scrutiny. Within the realm of MAGMA, pathways of significance were enriched, unmasking nine pleiotropic genes, including HIST1H1B, HIST1H4L, and HIST1H2BL. Leveraging eQTL insights from esophageal and lung tissues, alongside whole blood, unveiled 26 gene connections, enlisting TERT, NKAPL, RAD52, BTN3A2, GABBR1, CLPTM1L, and TRIM27. Further, a pan-cancer exploration of the consolidated genes was undertaken. Ultimately, wielding MR analysis, our appraisal of the causal nexus between esophageal carcinoma and lung carcinoma underscored the absence of a bidirectional causal affiliation. Conclusions This inquiry furnishes profound insights into the intricate genetic nexus uniting lung carcinoma and esophageal carcinoma. Through the prism of LDSC for genetic correlation, an intricate analysis delineating loci and genes, and a bidirectional MR schema for causal evaluation, we unveil shared genetic propensities and regulatory substrates. These revelations proffer nascent prompts and targets, beckoning a deeper foray into the genetic underpinnings of lung carcinoma and esophageal carcinoma, thus catalyzing the evolution of prophylactic and remedial strategies.