Inherited variations in human pigmentation-related genes modulate cutaneous melanoma risk and clinicopathological features in Brazilian population

Author(s):Show less -

Lourenco, Gustavo Jacob ^[1] ; Oliveira, Cristiane ^[1] ; Carvalho, Benilton Sa ^[2] ; Torricelli, Caroline ^[1] ; Silva, Janet Keller ^[1] ; Boas Gomez, Gabriela Vilas ^[1] ; Rinck-Junior, Jose Augusto ^{[3, 4]} ; Oliveira, Wesley Lima ^[1] ; Vazquez, Vinicius Lima ^[5] ; Serrano, Sergio Vicente ^[6] ; Moraes, Aparecida Machado ^[4] ; Passos Lima, Carmen Silvia ^{[1, 4]}

Affiliation

^[1] Univ Estadual Campinas, Fac Med Sci, Lab Canc Genet, Campinas, SP - Brazil

^[2] Univ Estadual Campinas, Inst Math Stat & Comp Sci, Dept Stat, Campinas, SP - Brazil

^[3] AC Camargo Canc Ctr, Sao Paulo, SP - Brazil

^[4] Univ Estadual Campinas, Fac Med Sci, Dept Internal Med, Clin Oncol Serv, Rua Alexander Fleming 181, Campinas, SP - Brazil

^[5] Barretos Canc Hosp, Melanoma & Sarcoma Surg Dept, Barretos, SP - Brazil

^[6] Barretos Canc Hosp, Dept Med Oncol, Barretos, SP - Brazil

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 10, n. 1 JUL 22 2020.
• Web of Science Citations: 0

Abstract

Ultraviolet light exposure and cutaneous pigmentation are important host risk factors for cutaneous melanoma (CM), and it is well known that inherited ability to produce melanin varies in humans. The study aimed to identify single-nucleotide variants (SNVs) on pigmentation-related genes with importance in risk and clinicopathological aspects of CM. The study was conducted in two stages. In stage 1, 103 CM patients and 103 controls were analyzed using Genome-Wide Human SNV Arrays in order to identify SNVs in pigmentation-related genes, and the most important SNVs were selected for data validation in stage 2 by real-time polymerase-chain reaction in 247 CM patients and 280 controls. ADCY3 c.675+9196T>G, CREB1 c.303+373G>A, and MITF c.938-325G>A were selected for data validation among 74 SNVs. Individuals with CREB1 GA or AA genotype and allele ``A{''} were under 1.79 and 1.47-fold increased risks of CM than others, respectively. Excesses of CREB1 AA and MITF AA genotype were seen in patients with tumors at Clark levels III to V (27.8% versus 13.7%) and at III or IV stages (46.1% versus 24.9%) compared to others, respectively. When compared to others, patients with ADCY3 TT had 1.89 more chances of presenting CM progression, and those with MITF GA or AA had 2.20 more chances of evolving to death by CM. Our data provide, for the first time, preliminary evidence that inherited abnormalities in ADCY3, CREB1, and MITF pigmentation-related genes, not only can increase the risk to CM, but also influence CM patients' clinicopathological features. (AU)

• FAPESP's process: 16/02193-9 - Functional analysis of polymorphic genes enrolled in melanogenesis in cutaneous melanoma
• Grantee: Gustavo Jacob Lourenço
• Support type: Regular Research Grants
• FAPESP's process: 12/15880-3 - Identification of inherited susceptibility genes for cutaneous melanoma by large scale genotyping
• Grantee: Carmen Silvia Passos Lima
• Support type: Regular Research Grants
• FAPESP's process: 12/16617-4 - Identification of inherited susceptibility genes for cutaneous melanoma by large scale genotyping
• Grantee: Cristiane de Oliveira
• Support type: Scholarships in Brazil - Doctorate