A Scoping Review of the Methodology Used in Studies of Genetic Influences on the Development of Keloid or Hypertrophic Scarring in Adults and Children After Acute Wounding

Significance: Keloid and hypertrophic scarring are common following acute wounds. However, the variability in scarring outcomes between individuals and in particular, the association between genetic factors and scarring, is not well understood. This scoping review aims to summarize the methodology used in studies of genetic influences on the development of keloid or hypertrophic scarring in adults and children after acute wounding. The objectives were to determine the study designs used, the characteristics of participants included, the tools used to assess scarring and the length of follow-up after wounding. Recent Advances: The review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Medline, Excerpta Medica Database (EMBASE), Web of Science, Biosciences Information Service (BIOSIS), Prospective Register of Systematic Reviews (PROSPERO), The Human Genetic Epidemiology (HuGE) Navigator (database of genetic association studies), and the genome-wide association study Catalog were searched from January 2008 to April 2020. Cohort studies and case–control studies that examined the association between one or more genetic variations and the development of keloid or hypertrophic scarring were eligible for inclusion. A narrative synthesis that grouped studies by wound type was conducted. Critical Issues: Nine studies met the inclusion criteria (five in burns, four surgical wounds, and none in other types of acute wounds). Seven assessed hypertrophic scarring, one keloid scarring, and one both scar types. Seven studies used a prospective cohort design. All studies used subjective methods (clinician or patient observation) to assess scarring. There was considerable variation in how scar scales were operationalized. Future Directions: This review identified a small body of evidence on genetic susceptibility to scarring after acute wounding. Further studies are needed, and in a wide range of populations, including patients with wounds caused by trauma.