title: Association of TGFβ1 and clinical factors with scar outcome following melanoma excision.
abstract: All patients with primary cutaneous malignant melanoma undergo surgical excision to remove the tumour, resulting in scar formation. There is marked variation in the aesthetic appearance of scars following surgery but limited knowledge about the genetic factors affecting non-keloid, surgical scar outcomes. This study aimed to investigate the role of known clinical factors and genetic polymorphisms in pigmentation and wound repair genes in non-keloid scar outcome, following melanoma excision. Participants were 202 cases who underwent a standardized scar assessment following surgical melanoma excision and provided a DNA sample. Genetic association analyses between single nucleotide polymorphisms (SNPs) from 24 candidate genes and scar outcome data were performed, controlling for relevant clinical factors. Following adjustment for multiple testing, SNP rs8110090 in TGFβ1 was significantly associated with both the primary scar outcome (a combination score reflecting vascularity, height and pliability, p = 0.0002, q = 0.01) and the secondary scar outcome (a combination score reflecting vascularity, height, pliability and pigmentation, p = 0.0002, q = 0.006). The minor allele G was associated with a poorer scar outcome. Younger age, time elapsed since excision, absence of kidney failure and eczema, presence of thyroid problems and infection were also associated with poorer scar outcome and were adjusted for in the final model, along with scar site. Results from this study suggest that genes involved in wound healing may play a role in determining scar outcome. Associations observed between scar outcome and clinical factors reinforce current clinical knowledge regarding factors affecting scarring. Replication studies in larger samples are warranted and will improve our understanding of the underlying mechanisms of scarring, potentially help to identify patients at risk of poor scar outcomes.
authors.affiliation: Centre for Genetic Epidemiology and Biostatistics, The University of Western Australia, M409, 35 Stirling Highway, Crawley, WA, 6009, Australia. sarah.ward@uwa.edu.au
authors.forename: Sarah V
authors.initials: SV
authors.lastname: Ward
authors.forename: G
authors.initials: G
authors.lastname: Cadby
authors.forename: J S
authors.initials: JS
authors.lastname: Heyworth
authors.forename: M W
authors.initials: MW
authors.lastname: Fear
authors.forename: H J
authors.initials: HJ
authors.lastname: Wallace
authors.forename: J M
authors.initials: JM
authors.lastname: Cole
authors.forename: F M
authors.initials: FM
authors.lastname: Wood
authors.forename: L J
authors.initials: LJ
authors.lastname: Palmer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017439:Cicatrix, Hypertrophic / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000601:surgery*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012878:Skin Neoplasms / Q000235:genetics / Q000601:surgery*; D012880:Skin Pigmentation / Q000235:genetics; D011795:Surveys and Questionnaires; D053773:Transforming Growth Factor beta1 / Q000235:genetics*; D016896:Treatment Outcome; D014945:Wound Healing / Q000235:genetics*; D055815:Young Adult
chemical_list: C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1