title: MITF E318K's effect on melanoma risk independent of, but modified by, other risk factors.
abstract: A rare germline variant in the microphthalmia-associated transcription factor (MITF) gene, E318K, has been reported as associated with melanoma. We confirmed its independent association with melanoma [odds ratio (OR) 1.7, 95% confidence interval (CI) = 1.1, 2.7, P = 0.03]; adjusted for age, sex, center, age × sex interaction, pigmentation characteristics, family history of melanoma, and nevus density). In stratified analyses, carriage of MITF E318K was associated with melanoma more strongly in people with dark hair than fair hair (P for interaction, 0.03) and in those with no moles than some or many moles (P for interaction, <0.01). There was no evidence of interaction between MC1R 'red hair variants' and MITF E318K. Moreover, risk of melanoma among carriers with 'low risk' phenotypes was as great or greater than among those with 'at risk' phenotypes with few exceptions.
authors.affiliation: Departments of Internal Medicine and Dermatology, University of New Mexico, Albuquerque, NM, USA.
authors.forename: Marianne
authors.initials: M
authors.lastname: Berwick
authors.forename: Jamie
authors.initials: J
authors.lastname: MacArthur
authors.forename: Irene
authors.initials: I
authors.lastname: Orlow
authors.forename: Peter
authors.initials: P
authors.lastname: Kanetsky
authors.forename: Colin B
authors.initials: CB
authors.lastname: Begg
authors.forename: Li
authors.initials: L
authors.lastname: Luo
authors.forename: Anne
authors.initials: A
authors.lastname: Reiner
authors.forename: Ajay
authors.initials: A
authors.lastname: Sharma
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Armstrong
authors.forename: Anne
authors.initials: A
authors.lastname: Kricker
authors.forename: Anne E
authors.initials: AE
authors.lastname: Cust
authors.forename: Loraine D
authors.initials: LD
authors.lastname: Marrett
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Gruber
authors.forename: Hoda
authors.initials: H
authors.lastname: Anton-Culver
authors.forename: Roberto
authors.initials: R
authors.lastname: Zanetti
authors.forename: Stefano
authors.initials: S
authors.lastname: Rosso
authors.forename: Richard P
authors.initials: RP
authors.lastname: Gallagher
authors.forename: Terence
authors.initials: T
authors.lastname: Dwyer
authors.forename: Alison
authors.initials: A
authors.lastname: Venn
authors.forename: Klaus
authors.initials: K
authors.lastname: Busam
authors.forename: Lynn
authors.initials: L
authors.lastname: From
authors.forename: Kirsten
authors.initials: K
authors.lastname: White
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Thomas
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution; D016384:Consensus Sequence; D005787:Gene Frequency; D006200:Hair Color / Q000235:genetics; D006801:Humans; D008545:Melanoma / Q000453:epidemiology / Q000235:genetics*; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics* / Q000378:metabolism; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009378:Neoplasms, Multiple Primary / Q000453:epidemiology / Q000235:genetics; D009508:Nevus, Pigmented / Q000453:epidemiology / Q000235:genetics; D016017:Odds Ratio; D010641:Phenotype; D017354:Point Mutation; D011499:Protein Processing, Post-Translational / Q000235:genetics; D012306:Risk; D012307:Risk Factors; D012878:Skin Neoplasms / Q000453:epidemiology / Q000235:genetics; D058207:Sumoylation / Q000235:genetics
chemical_list: C497234:MITF protein, human; D051739:Microphthalmia-Associated Transcription Factor; D009363:Neoplasm Proteins
keywords: Case-controlstudy; MITF; melanoma; risk factors; single nucleotide polymorphism