We investigated the risks of 4 types of skin cancer among patients with neurofibromatosis type 1, a multisystemic autosomal dominant genetic syndrome characterized by loss of neurofibromin.
The risks of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), keratinocyte carcinoma and melanoma were found to be higher among a group of 4,122 patients who had neurofibromatosis type 1 (NF1), according to the results of a new study in JAMA Dermatology.
Patients who have NF1 lack neurofibromin, a tumor suppressor gene, and so can develop benign tumors of the skin, eyes and nervous system and have a higher risk of cancer of the nervous system or other solid organs, wrote the study researchers.
“Although patients with NF1 often present to dermatologists for skin problems, their risk of BCC, SCC, and melanoma is unclear,” the researchers wrote. “Biallelic loss of NF1 (OMIM 613113) leads to hyperactivation of RAS signaling pathways”.
The Clinformatics Data Mart provided data for this retrospective cohort study that took place between January 1, 2009 and March 31, 2021. The mean (SD) age of patients was 47 (18) years and 55.5% of the study participants were women; each patient with NF1 was matched with up to 10 patients (n = 41,064) who did not have the genetic syndrome. A diagnosis of NF1 was shown using diagnostic codes from the International Classification of Diseases, Ninth Revision or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision.
Patients with NF1 had higher odds of BCC, SCC, and melanoma compared to the non-NF1 group. For BCC, the risk was 30% greater (odds ratio [OR], 1.30; 95% CI, 1.10-1.53; P = 0.02); for keratinocyte carcinoma, 31% more (OR, 1.31; 95% CI, 1.15-1.51; P < .001); for SCC, 32% more (OR, 1.30; 95% CI, 1.07-1.63; P = .008); and for melanoma, 127% higher (OR, 2.27; 95% CI, 1.75-2.93; P < .001).
Ages 18 to 34 were the most frequent, with 30.9% in the NF1 group and 31.1% in the non-NF1 group, followed by patients aged 55 to 64 (16.9%) and 45 to 54 (15.9%) years and from 35 to 34 years. 44 (16.9%) and from 45 to 54 years (15.7%), respectively. Asian, black, and Hispanic patients were outnumbered by white patients in each group, 25% versus 75% in the NF1 group and 24.7% versus 75.2% in the non-NF1 group.
A subanalysis comparing rates of melanoma and keratinocyte carcinoma between white patients and Asian, black, or Hispanic patients found higher overall risks of both cancers among those with NF1, but there were notable differences in these risks between ethnicities studied
While white patients had a 116% higher risk of melanoma, Asians had a 150% higher risk, Hispanics a 193% higher risk, and blacks a 344% higher risk. And while white and Asian patients had a comparable increased risk of keratinocyte carcinoma, at 25% each, Hispanic patients had a 103% higher risk and black patients a 102% higher risk.
“Whole-exome sequencing has established NF1 as the third most frequently mutated gene in melanomas,” the researchers noted. “About 12% to 18% of melanomas and 45% to 93% of desmoplastic melanomas harbor NF1 alterations.”
In addition, NF1 deletion has been linked to RAS activation in melanogenesis and SCC pathogenesis, while RAS/MAPK activation has been associated with drug resistance in certain subtypes of BCC, they pointed out
“These results highlight the role of germline RAS pathway hyperactivation in skin carcinogenesis. Whether photoprotection mitigates skin cancer development in NF1 patients is unknown,” they concluded. “However, quantifying skin cancer risk may empower clinicians to educate patients with NF1 and guide dermatologic management.”
reference
Trinh P, Li S, Sarin K. Neurofibromatosis type 1 and skin cancer risk. JAMA Dermatol. 2022;158(10):1214-1216. doi:10.1001/jamadermatol.2022.3083