Melanocortin-1 Receptor Gene Variants Determine the Risk of Nonmelanoma Skin Cancer Independently of Fair Skin and Red Hair
| Autor: | Bastiaens, Maarten T., Ter Huurne, Jeannet A.C., Kielich, Christine, Gruis, Nelleke A., Westendorp, Rudi G.J., Vermeer, Bert Jan, Bavinck, Jan Nico Bouwes, Amsterdam, Nathalie Van, Bergman, Wilma, Berkhout, Marjo, Boxman, Ingeborg, Broer, René, Bruijn, Jan Anthonie, Crijns, Marianne, Feltkamp, Mariet, Hertog, Sofie De, Hoefnagel, Juliette, Kennedy, Kees, Kuijken, Iris, Lavrijsen, Sjan, Mulder, Linda, Polderman, Marloes, Van Praag, Marinus, Schegget, Jan Ter, Sterk, Caesar, Struijk, Linda, Wensveen, Christianne |
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| Jazyk: | angličtina |
| Rok vydání: | 2001 |
| Předmět: |
Oncology
Adult Male medicine.medical_specialty Skin Neoplasms Genotype Molecular Sequence Data Skin Pigmentation Biology Interviews as Topic Gene Frequency Internal medicine medicine Genetics Odds Ratio Life Science Humans Genetics(clinical) Genetic Predisposition to Disease Allele Risk factor Hair Color Physical Examination Genetics (clinical) Alleles Polymorphism Single-Stranded Conformational Aged integumentary system Models Genetic Melanoma Receptors Melanocortin Genetic Variation Odds ratio Articles Middle Aged medicine.disease Endocrinology Amino Acid Substitution Receptors Corticotropin Carcinoma Basal Cell Relative risk Mutation Carcinoma Squamous Cell Female Skin cancer Melanocortin 1 receptor |
| Zdroj: | American Journal of Human Genetics 68 (2001) 4 American Journal of Human Genetics, 68(4), 884-894 |
| ISSN: | 0002-9297 |
| Popis: | Melanocortin-1 receptor (MC1R) gene variants are associated with fair skin and red hair and, independently of these, with cutaneous malignant melanoma. The association of MC1R gene variants with nonmelanoma skin cancer is largely unknown. A total of 838 subjects were included in the present study: 453 patients with nonmelanoma skin cancer and 385 subjects with no skin cancer. The coding sequence of the human MC1R gene was tested using single-stranded conformation polymorphism analysis followed by sequencing of unknown variants. Risk of skin cancer dependent on the various MC1R gene variants was estimated using the exposure odds ratio. We investigated whether subjects with MC1R variant alleles were at increased risk of developing nonmelanoma skin cancer and, if so, whether this increased risk was mediated by fair skin and red hair. A total of 27 MC1R gene variants were found. The number of carriers of one, two, or three MC1R gene variants was 379 (45.2%), 208 (24.8%), and 7 (0.9%), respectively. A strong association between MC1R gene variants and fair skin and red hair was established, especially the variants Arg151Cys and Arg160Trp (P < .0001). Carriers of two variant alleles were at increased risk for developing cutaneous squamous cell carcinoma (odds ratio 3.77; 95% confidence interval [CI] 2.11-6.78), nodular basal cell carcinoma (odds ratio 2.26; 95% CI 1.45-3.52), and superficial multifocal basal cell carcinoma (odds ratio 3.43; 95% CI 1.92-6.15), compared with carriers of two wild-type alleles. Carriers of one variant allele had half the risk. The highest relative risks of nonmelanoma skin cancer were found in carriers of the Asp84Glu, His260Pro, and Asp294His variant alleles, and the risk was only slightly lower for carriers of the Va160Leu, Va192Met, Arg142His, Arg151Cys, and Arg160Trp variant alleles. When subjects were stratified by skin type and hair color, analysis showed that these factors did not materially change the relative risks. These findings indicate that MC1R gene variants are important independent risk factors for nonmelanoma skin cancer. |
| Databáze: | OpenAIRE |
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