Risk of cutaneous malignant melanoma (CMM) is increased in sun-exposed whites, particularly those with a pale complexion. This study was designed to investigate the relationship of the melanocortin-1 receptor (MC1R) genotype to CMM risk, controlled for pigmentation phenotype. We report the occurrence of five common MC1R variants in an Australian population-based sample of 460 individuals with familial and sporadic CMM and 399 control individuals-and their relationship to such other risk factors as skin, hair, and eye color; freckling; and nevus count. There was a strong relationship between MC1R variants and hair color and skin type. Moreover, MC1R variants were found in 72% of the individuals with CMM, whereas only 56% of the control individuals carried at least one variant (P<.001), a finding independent of strength of family history of melanoma. Three active alleles (Arg151Cys, Arg160Trp, and Asp294His), previously associated with red hair, doubled CMM risk for each additional allele carried (odds ratio 2.0; 95% confidence interval 1. 6-2.6). No such independent association could be demonstrated with the Val60Leu and Asp84Glu variants. Among pale-skinned individuals alone, this association between CMM and MC1R variants was absent, but it persisted among those reporting a medium or olive/dark complexion. We conclude that the effect that MC1R variant alleles have on CMM is partly mediated via determination of pigmentation phenotype and that these alleles may also negate the protection normally afforded by darker skin coloring in some members of this white population.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1288324 | PMC |
| http://dx.doi.org/10.1086/302711 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Self-assessed improved sun protection after diagnosis of melanoma is associated with improved survival.
Clin Exp Dermatol
December 2024
Department of Dermatology, Medical University of Vienna, Vienna, Austria.
Background: Although ultraviolet radiation is the most important risk factor for skin cancer in general, its role in disease control after the diagnosis of melanoma remains to be elucidated.
Objectives: To analyse the association between survival and self-assessed sun protection behaviour after a melanoma diagnosis.
Methods: This was a questionnaire-based pilot study.
Systematic proteome-wide Mendelian randomization to prioritize causal plasma proteins for skin cancers.
Commun Biol
December 2024
Department of Computational Diagnostic Radiology and Preventive Medicine, The University of Tokyo Hospital, Tokyo, Japan.
Skin cancer is one of the most common cancers worldwide. Some risk factors including sun exposure and MC1R variants are recognized; however, the identification of additional genetic factors is essential for the development of novel therapeutic strategies. Here, we conducted a proteome-wide Mendelian randomization (MR) using plasma protein quantitative trait loci (pQTLs) from a published study and the UK Biobank genome-wide association study (GWAS) of skin cancers.
View Article and Find Full Text PDFThe melanocortin receptor genes are linked to and associated with the risk of polycystic ovary syndrome in Italian families.
J Ovarian Res
December 2024
Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA, 17033, USA.
Article Synopsis
- - Polycystic ovary syndrome (PCOS) is a common hormonal disorder in women, influenced by genetic and environmental factors, especially connected to the hypothalamic-pituitary-adrenal (HPA) axis genes.
- - A study investigated various single nucleotide polymorphisms (SNPs) in five melanocortin receptor genes within 212 Italian families with PCOS, finding significant associations with certain SNPs in MC1R, MC2R, MC3R, and MC5R.
- - This research highlights the role of specific melanocortin receptor genes in PCOS, marking a new connection, while emphasizing the need for further functional studies to confirm these findings.
Complete Genomic Landscape Reveals Hidden Evolutionary History and Selection Signature in Asian Water Buffaloes (Bubalus bubalis).
Adv Sci (Weinh)
December 2024
State Key Laboratory of Animal Biotech Breeding, National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China.
Article Synopsis
- Researchers sequenced 470 genomes of domesticated river and swamp buffaloes and their wild ancestors to investigate the genetic factors influencing domestication and productivity in Asian water buffaloes.* -
- Wild swamp buffaloes maintain ancestral morphology, while river buffaloes show distinct traits, yet both have genomes that align closely with wild counterparts; genetic diversity varies significantly across regions.* -
- Key findings indicate that artificial selection has led to significant genetic adaptations in traits like reproduction, milk production, and coat color, highlighting how domestication affects evolutionary changes in these animals.*
Melanocortin 1 receptor mediates melanin production by interacting with the BBSome in primary cilia.
PLoS Biol
December 2024
Center for Cell Structure and Function, Shandong Provincial Key Laboratory of Animal Resistance Biology, College of Life Sciences, Shandong Normal University, Jinan, China.
Production of melanin pigments is a protective mechanism of the skin against ultraviolet (UV)-induced damage and carcinogenesis. However, the molecular basis for melanogenesis is still poorly understood. Herein, we demonstrate a critical interplay between the primary cilium and the melanocortin 1 receptor (MC1R) signaling.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!