Risk of cancer development in patients with keloids

Abstract

Keloid is a skin disease characterized by exaggerated scar formation, excessive fibroblast proliferation, and excessive collagen deposition. Cancers commonly arise from a fibrotic microenvironment; e.g., hepatoma arises from liver cirrhosis, and oral cancers arise from submucosal fibrosis. As keloids are a prototypic fibroproliferative disease, this study investigated whether patients with keloids have an increased cancer risk. In a matched, population-based study, first 17,401 patients treated for keloids during 1998–2010 with 69,604 controls without keloids at a ratio of 1:4 were evaluated. The association between keloids and risk of cancer was estimated by logistic regression or Cox proportional hazard regression models after adjustment of covariates. In total, 893 first-time cases of cancer were identified in the 17,401 patients with keloids. The overall cancer risk was 1.49-fold higher in the keloids group compared to controls. Regarding specific cancers, the keloids group, had a significantly higher risk of skin cancer compared to controls (Relative risk = 1.73). The relative risk for skin cancer was even higher for males with keloids (Relative risk = 2.16). Further stratified analyses also revealed a significantly higher risk of developing pancreatic cancer in female patients with keloids compared to controls (Relative risk = 2.19) after adjustment for known pancreatic cancer risk factors. This study indicates that patients with keloids have a higher than normal risk for several cancer types, especially skin cancers (both genders) and pancreatic cancer (females). Therefore, patients with keloids should undergo regular skin examinations, and females with keloids should regularly undergo abdominal ultrasonography.

The m6A-methylated mRNA pattern and the activation of the Wnt signaling pathway under the hyper-m6A-modifying condition in the keloid

“…It is difficult to achieve a complete cure for this disease. Moreover, recent studies have indicated that patients with keloids have a higher risk of developing various cancers than normal individuals ( Lu et al, 2021 ). In a matched, population-based regression analysis study (17,401 patients with keloid vs. 69,604 controls), Ying-Yi et al have shown that the overall cancer risk was 1.49-fold higher in the keloid group than controls ( Lu et al, 2021 ).…”

A Signature of Genes Featuring FGF11 Revealed Aberrant Fibroblast Activation and Immune Infiltration Properties in Keloid Tissue

“…Keloids grown in certain areas can also become symptomatic by limiting joint mobility and even causing deformity. Although keloids have been considered benign, growing evidence shows that the underlying pathogenesis and recurrent episodes entail regular skin examinations as the keloid-prone population faces a significantly higher risk of developing skin cancer, especially males [ 11 ].…”

“…Although keloid is labeled as an abnormal but benign dermal growth where excessive scar tissue results from failed suppression of wound healing, it resembles malignant tumor cells in terms of its hyperproliferative nature and capability of invasion. There is also growing evidence showing that keloid-prone populations, especially males, face a significantly higher risk of developing skin malignancies [ 11 ]. This, along with the cosmetic burden and disabling potential of large keloids, entails more advanced, effective treatment regimens.…”

Epigenetic Influences on Wound Healing and Hypertrophic-Keloid Scarring: A Review for Basic Scientists and Clinicians

“…Whereas hypermethylation can cause downregulation and inhibit transcription and synthesis of tumor suppressor proteins, hypomethylation can destabilize the DNA and be a precursor for oncogenesis. The significance of oncogenesis in the development of keloids is underscored by findings that aberrant methylation of tumor suppressor genes appears to be a factor in the development of keloids [ 15 ] and patients affected by keloids exhibit increased incidences of various skin cancers [ 16 ]. Figure 2 summarizes the role of DNA methylation in the formation of keloids.…”

“…Inhibition of migration and proliferation of keratinocytes adversely affect wound epithelialization and, ultimately, wound healing. ROS is associated with increased expression of the GLUT1 glucose transporter in the skin of patients affected by diabetes [ 26 ], psoriasis [ 27 ], and keloids [ 16 ], thereby providing a biochemical marker for oxidative stress and the potential for developing fibroproliferative lesions. Increased ROS in fibroblasts from keloid scar tissue exposed to hypoxia [ 28 ] also suggests that oxidative stress likely plays an important role in the development and maintenance of keloids.…”