GSTP1 does not modify MC1R effects on melanoma risk

Abstract

Additional Supporting Information may be found online in the supporting information tab for this article. L E T T E R S T O T H E E D I T O R GSTP1 does not modify MC1R effects on melanoma risk 1 | BACKGROUNDGlutathione S-transferases (GSTs) are a group of enzymes that act to detoxify reactive oxygen species resulting from oxidative stress processes and melanin production. GSTP1 is a polymorphic gene encoding variant proteins involved in metabolism. The role of the rs1695*A/G GSTP1 Ile105Val polymorphism in cutaneous malignant melanoma (CMM) susceptibility remains controversial. Two recent meta-analyses reported that the GSTP1 105Val allele was associated with an increased risk of CMM.1,2 However, it was concluded by the authors of both publications that additional studies with larger cohorts were required.The melanocortin 1 receptor (MC1R) gene encodes a G-protein coupled receptor involved in the regulation of melanin production and the response to solar ultraviolet. 3 MC1R RHC-variant alleles exercise major influence on hair colour, skin colour and sun sensitivity. The association between MC1R and susceptibility to CMM and skin cancer in general has been described previously. 4,5 A 2011 Spanish study reported that the GSTP1 polymorphism was associated with light coloured hair and increased CMM risk. Furthermore, the authors described a greater penetrance of CMM risk when the GSTP1 105Val allele was combined with MC1R RHC-variant alleles.6,7 | QUESTIONS ADDRESSEDThis study has further examined the association between rs1695*A/G GSTP1 Ile105Val polymorphism and CMM. In addition, we examined the previously described effect modification of the combination of GSTP1 Ile105Val with MC1R RHC-variant alleles in a cohort of Queensland control and CMM cases and CMM control and patient samples from Germany. This study included the largest population to date, a total of 27 574 participants. Six GSTP1 polymorphisms were examined to assess for a potential effect on CMM risk (Table 1). GSTP1 rs4891 was in strong linkage disequilibrium with rs1695 (r 2 =0.92, Table S1). Although previous studies have suggested the involvement of rs1695 in CMM risk (also apparent when stratified by study, MC1R variant genotypes designated using WT, r and R allele classification and risk of CMM (Table 2). These effects were not modified by GSTP1 rs1695 genotype (A/A, A/G, G/G) in the stratified analysis (overall P=0.79). This result was also confirmed when restricted to MC1R Arg151Cys genotype (WT/WT, WT/R, R/R), the MC1R allele of highest penetrance for CMM and red hair colour (Table S3). Moreover, examination of each MC1R allele individually did not show any interaction with GSTP1 rs1695 genotype and CMM risk (Table S4). | EXPERIMENTAL DESIGN & RESULTSThe reported association of rs1695 and light hair colour 6 was not seen in our analysis. However, the rs1138272 GSTP1 Ala114ValSNP showed weak association with darker hair colour in the BTNS | LETTERS TO THE EDITOR | CONCLUSIONSThe role of GSTP1 polymorphism in CMM has been examined in sev...

Phenotypic and genotypic analysis of amelanotic and hypomelanotic melanoma patients

“…In this study, we aimed to identify the clinical phenotype and genetic susceptibility of patients with AHM compared to pigmented melanoma drawn from the Brisbane Naevus Morphology Study (BNMS). [12][13][14][15] This paper demonstrates how a genotypic risk association profile can be constructed for such patients (Fig. 1).…”

“…A minimum of 2.5 lg of DNA was processed at the UQ Centre for Clinical Genomics (UQCCG) at the Translational Research Institute (TRI) on an Illumina Infinium HumanCoreExome-24 Microarray. 12,14,17 426 of 436 case samples and all 692 controls were of sufficient quality for genotyping. We specifically looked at seven candidate pigmentation SNPs with known effects on phenotype and melanoma-associated genes with common tagging SNPs for risk haplotypes.…”

Iris pigmented lesions as a marker of cutaneous melanoma risk: an Australian case-control study

“…Genomic DNA was extracted from 2 mL of saliva collected using an Oragene‐DNA self‐collection kit (DNA Genotek, Ottawa, ON, Canada) . A minimum of 2·5 μg of DNA was processed at the UQ Centre for Clinical Genomics on an Illumina Infinium HumanCoreExome‐24 Microarray (Illumina, San Diego, CA, U.S.A.) …”

“…A total of 1254 individuals volunteered for clinical examination from October 2009 to November 2015 as part of the Brisbane Naevus Morphology Study (BNMS), an epidemiological study of naevus and melanoma genes in participants recruited from South-East Queensland. 18,19 Participants were recruited from the Melanoma Unit and Dermatology Department of the Princess Alexandra Hospital (Brisbane, Australia), private dermatology clinics, the Brisbane Longitudinal Twin Study (BLTS) and the QSkin Study. 20 There was no age limit, but participants who were unable to stand for the duration of the skin imaging were excluded from the study.…”

“…18 A minimum of 2Á5 lg of DNA was processed at the UQ Centre for Clinical Genomics on an Illumina Infinium HumanCoreExome-24 Microarray (Illumina, San Diego, CA, U.S.A.). 19…”