Inherited variants in the MC1R gene and survival from cutaneous melanoma: a BioGenoMEL study

نویسندگان

  • John R Davies
  • Juliette Randerson-Moor
  • Kairen Kukalizch
  • Mark Harland
  • Rajiv Kumar
  • Srinivasan Madhusudan
  • Eduardo Nagore
  • Johan Hansson
  • Veronica Höiom
  • Paola Ghiorzo
  • Nelleke A Gruis
  • Peter A Kanetsky
  • Judith Wendt
  • Dace Pjanova
  • Susana Puig
  • Philippe Saiag
  • Dirk Schadendorf
  • Nadem Soufir
  • Ichiro Okamoto
  • Paul Affleck
  • Zaida García-Casado
  • Zighereda Ogbah
  • Aija Ozola
  • Paola Queirolo
  • Antje Sucker
  • Jennifer H Barrett
  • Remco van Doorn
  • D Timothy Bishop
  • Julia Newton-Bishop
چکیده

Inherited MC1R variants modulate MITF transcription factor signaling, which in turn affects tumor cell proliferation, apoptosis, and DNA repair. The aim of this BioGenoMEL collaborative study in 10 melanoma cohorts was to test the hypothesis that inherited variants thereby moderate survival expectation. A survival analysis in the largest cohort (Leeds) was carried out adjusting for factors known to impact on survival. The results were then compared with data from nine smaller cohorts. The absence of any consensus MC1R alleles was associated with a significantly lower risk of death in the Leeds set (HR, 0.64; 95% CI, 0.46-0.89) and overall in the 10 data sets (HR, 0.78; 95% CI, 0.65-0.94) with some support from the nine smaller data sets considered together (HR, 0.83; 95% CI, 0.67-1.04). The data are suggestive of a survival benefit for inherited MC1R variants in melanoma patients.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Ocular melanoma is not associated with CDKN2A or MC1R variants--a population-based study.

Germline variants in the melanocortin 1 receptor gene (MC1R) and the p16 gene (CDKN2A) are associated with an increased risk of cutaneous melanoma. The frequency of these germline variants was examined in a population-based, incident series of 62 ocular melanoma cases and ethnicity-matched population controls. In both cases and controls, 59% of individuals carried at least one MC1R variant and ...

متن کامل

Inherited Variation at MC1R and Histological Characteristics of Primary Melanoma

Variation in the melanocortin-1receptor (MC1R) gene is associated with pigmentary phenotypes and risk of malignant melanoma. Few studies have reported on MC1R variation with respect to tumor characteristics, especially clinically important prognostic features. We examined associations between MC1R variants and histopathological melanoma characteristics. Study participants were enrolled from nin...

متن کامل

Characterization of melanocortin-1 receptor gene variants in uveal melanoma patients.

PURPOSE Allelic variations of the melanocortin-1 receptor (MC1R) gene have been linked to red hair and sun-sensitive skin types and may play a role in the susceptibility to develop cutaneous malignant melanoma (CMM). To define the role of MC1R gene in uveal melanoma, a case control study was performed, in which the presence of MC1R gene variations in uveal melanoma patients was compared with th...

متن کامل

[Phenotypic and histologic characteristics of cutaneous melanoma in patients with melanocortin-1 receptor polymorphisms].

BACKGROUND The melanocortin-1 receptor (MC1R) is an important risk factor for melanoma due to its role in the production of melanin in response to sun exposure. OBJECTIVES To analyze the phenotypic and histologic characteristics of cutaneous melanoma in patients carrying mutations in MC1R and assess the influence of sun exposure on the occurrence of melanoma. MATERIAL AND METHODS A total of...

متن کامل

Genomic expression differences between cutaneous cells from red hair color individuals and black hair color individuals based on bioinformatic analysis

The MC1R gene plays a crucial role in pigmentation synthesis. Loss-of-function MC1R variants, which impair protein function, are associated with red hair color (RHC) phenotype and increased skin cancer risk. Cultured cutaneous cells bearing loss-of-function MC1R variants show a distinct gene expression profile compared to wild-type MC1R cultured cutaneous cells. We analysed the gene signature a...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره 25  شماره 

صفحات  -

تاریخ انتشار 2012