GENETIC FACTORS OF PREDISPOSITION TO PATHOLOGICAL SCARRING AFTER SURGICAL INTERVENTIONS

Abstract

Hypertrophic and keloid scars complicate the healing of surgical wounds; however, existing genetic data have yet to provide a reliable basis for predicting their development in individual patients. Comparing findings across studies is challenging because inherited genetic variants and the molecular alterations observed in established scars reflect different stages of the pathological process. This study aimed to critically evaluate the genetic factors involved in scarring and to assess their potential utility for preoperative risk prediction. The analysis drew upon 43 sources – including official statistics, Russian clinical guidelines, original research, and reviews – identified through a search of PubMed, Europe PMC, and the websites of scientific journals and professional organizations (covering the period 2021–2026). The data were subjected to comparative analysis, systematization, and critical qualitative assessment, with careful consideration given to scar type, the origin of the injury, sample composition, and the independent replication of reported associations. Inherited genetic variants were examined separately from alterations in gene expression, while prognostic models were evaluated based on external validation and their incremental value beyond established clinical risk factors. By synthesizing genetic associations alongside the cellular and epigenetic mechanisms of scarring, this review distinguishes between factors related to hereditary susceptibility and those reflecting the state of the affected tissue. The primary limitations identified include the heterogeneity of scar phenotypes, insufficient reproducibility of findings, and a scarcity of data concerning surgical patients: out of 26 loci discovered through an analysis of 7,837 keloid cases and 1,593,009 control subjects, only 12 have been independently validated. To assess the practical utility of genetic information, it has been proposed to compare clinical, genetic, and combined models within independent cohorts of patients who have undergone similar surgical procedures, while evaluating hypertrophic and keloid outcomes separately.