Melanoma cases demonstrate increased carrier frequency of phenylketonuria/hyperphenylalanemia mutations

Joshua Arbesman, Sairekha Ravichandran, Pauline Funchain, Cheryl L. Thompson

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Identifying novel melanoma genetic risk factors informs screening and prevention efforts. Mutations in the phenylalanine hydroxylase gene (the causative gene in phenylketonuria) lead to reduced pigmentation in untreated phenylketonuria patients, and reduced pigmentation is associated with greater melanoma risk. Therefore, we sought to characterize the relationship between phenylketonuria carrier status and melanoma risk. Using National Newborn Screening Reports, we determined the United States phenylketonuria/hyperphenylalanemia carrier frequency in Caucasians to be 1.76%. We examined three publically available melanoma datasets for germline mutations in the phenylalanine hydroxylase gene associated with classic phenylketonuria and/or hyperphenylalanemia. Mutations were identified in 29/814 melanoma patients, with a carrier frequency of 3.56%. There was a twofold enrichment (p-value = 3.4 × 10−5) compared to the Caucasian frequency of hyperphenylalanemia/phenylketonuria carriers. These data demonstrate a novel association between phenylalanine hydroxylase carrier status and melanoma risk. Further, functional investigation is warranted to determine the link between phenylalanine hydroxylase mutations and melanomagenesis.

Original languageEnglish (US)
Pages (from-to)529-533
Number of pages5
JournalPigment Cell and Melanoma Research
Volume31
Issue number4
DOIs
StatePublished - Jul 2018

All Science Journal Classification (ASJC) codes

  • General Biochemistry, Genetics and Molecular Biology
  • Dermatology
  • Oncology

Fingerprint

Dive into the research topics of 'Melanoma cases demonstrate increased carrier frequency of phenylketonuria/hyperphenylalanemia mutations'. Together they form a unique fingerprint.

Cite this