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Influence of genes, nevi, and sun sensitivity on melanoma risk in a family sample unselected by family history and in melanoma-prone families.
J Natl Cancer Inst 2004; 96(10):785-95JNCI

Abstract

BACKGROUND

Few family studies have investigated the effects of genetic, environmental, and host factors on melanoma risk, and most have been restricted to high-risk families. We assessed the role of these factors on melanoma risk in two types of families: families ascertained through melanoma probands but unselected by family history and melanoma-prone families.

METHODS

Data on pigmentary traits, nevus phenotypes, exposure to sun, and reactions to sunlight were collected from 295 families unselected by family history and 53 melanoma-prone families. We modeled melanoma risk using a logistic regressive model incorporating the effect of a melanoma-predisposing gene, familial dependence, and potential risk factors (e.g., pigmentary traits, nevus phenotypes, history of sun exposure, skin reactions to sunlight). Maximum-likelihood estimates of the parameters of the regressive model were used to compute odds ratios associated with each risk factor and age-specific melanoma risk depending on the genotype at the melanoma-predisposing gene and the effects of risk factors. All statistical tests were two-sided.

RESULTS

In the families unselected by family history, there was statistically significant evidence (P<.001) for a dominant gene, with melanoma risk reaching 0.49 and 0.67 by age 80 years in male and female gene carriers, respectively. Melanoma risk was statistically significantly influenced by total nevi (odds ratio of hazard function [OR] = 5.81, 95% confidence interval [CI] = 3.47 to 8.99), sun exposure (OR = 5.37, 95% CI = 4.44 to 6.36), and sunburn interacting with the gene (OR = 26.31, 95% CI = 7.56 to 99.22 in gene carriers and OR = 1.67, 95% CI = 1.36 to 2.03 in noncarriers). Twenty of the 53 melanoma-prone families had cosegregating mutations in CDKN2A, a gene known to be associated with melanoma. In these 53 families, three risk factors in addition to CDKN2A mutations increased melanoma risk: dysplastic nevi (OR = 2.32, 95% CI = 2.08 to 2.58), total nevi (OR = 1.99, 95% CI = 1.61 to 2.20) and sunburn (OR = 5.16, 95% CI = 4.82 to 5.52).

CONCLUSIONS

Together, a melanoma-predisposing gene (identified as being CDKN2A in melanoma-prone families), number of nevi and/or dysplastic nevi, and sun-related covariates influence melanoma risk in both families unselected by family history and melanoma-prone families.

Authors+Show Affiliations

Institut National de la Santé et Recherche Médicale et Université d'Evry, Evry, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15150307

Citation

Chaudru, Valérie, et al. "Influence of Genes, Nevi, and Sun Sensitivity On Melanoma Risk in a Family Sample Unselected By Family History and in Melanoma-prone Families." Journal of the National Cancer Institute, vol. 96, no. 10, 2004, pp. 785-95.
Chaudru V, Chompret A, Bressac-de Paillerets B, et al. Influence of genes, nevi, and sun sensitivity on melanoma risk in a family sample unselected by family history and in melanoma-prone families. J Natl Cancer Inst. 2004;96(10):785-95.
Chaudru, V., Chompret, A., Bressac-de Paillerets, B., Spatz, A., Avril, M. F., & Demenais, F. (2004). Influence of genes, nevi, and sun sensitivity on melanoma risk in a family sample unselected by family history and in melanoma-prone families. Journal of the National Cancer Institute, 96(10), pp. 785-95.
Chaudru V, et al. Influence of Genes, Nevi, and Sun Sensitivity On Melanoma Risk in a Family Sample Unselected By Family History and in Melanoma-prone Families. J Natl Cancer Inst. 2004 May 19;96(10):785-95. PubMed PMID: 15150307.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Influence of genes, nevi, and sun sensitivity on melanoma risk in a family sample unselected by family history and in melanoma-prone families. AU - Chaudru,Valérie, AU - Chompret,Agnès, AU - Bressac-de Paillerets,Brigitte, AU - Spatz,Alain, AU - Avril,Marie-Françoise, AU - Demenais,Florence, PY - 2004/5/20/pubmed PY - 2004/6/4/medline PY - 2004/5/20/entrez SP - 785 EP - 95 JF - Journal of the National Cancer Institute JO - J. Natl. Cancer Inst. VL - 96 IS - 10 N2 - BACKGROUND: Few family studies have investigated the effects of genetic, environmental, and host factors on melanoma risk, and most have been restricted to high-risk families. We assessed the role of these factors on melanoma risk in two types of families: families ascertained through melanoma probands but unselected by family history and melanoma-prone families. METHODS: Data on pigmentary traits, nevus phenotypes, exposure to sun, and reactions to sunlight were collected from 295 families unselected by family history and 53 melanoma-prone families. We modeled melanoma risk using a logistic regressive model incorporating the effect of a melanoma-predisposing gene, familial dependence, and potential risk factors (e.g., pigmentary traits, nevus phenotypes, history of sun exposure, skin reactions to sunlight). Maximum-likelihood estimates of the parameters of the regressive model were used to compute odds ratios associated with each risk factor and age-specific melanoma risk depending on the genotype at the melanoma-predisposing gene and the effects of risk factors. All statistical tests were two-sided. RESULTS: In the families unselected by family history, there was statistically significant evidence (P<.001) for a dominant gene, with melanoma risk reaching 0.49 and 0.67 by age 80 years in male and female gene carriers, respectively. Melanoma risk was statistically significantly influenced by total nevi (odds ratio of hazard function [OR] = 5.81, 95% confidence interval [CI] = 3.47 to 8.99), sun exposure (OR = 5.37, 95% CI = 4.44 to 6.36), and sunburn interacting with the gene (OR = 26.31, 95% CI = 7.56 to 99.22 in gene carriers and OR = 1.67, 95% CI = 1.36 to 2.03 in noncarriers). Twenty of the 53 melanoma-prone families had cosegregating mutations in CDKN2A, a gene known to be associated with melanoma. In these 53 families, three risk factors in addition to CDKN2A mutations increased melanoma risk: dysplastic nevi (OR = 2.32, 95% CI = 2.08 to 2.58), total nevi (OR = 1.99, 95% CI = 1.61 to 2.20) and sunburn (OR = 5.16, 95% CI = 4.82 to 5.52). CONCLUSIONS: Together, a melanoma-predisposing gene (identified as being CDKN2A in melanoma-prone families), number of nevi and/or dysplastic nevi, and sun-related covariates influence melanoma risk in both families unselected by family history and melanoma-prone families. SN - 1460-2105 UR - https://www.unboundmedicine.com/medline/citation/15150307/Influence_of_genes_nevi_and_sun_sensitivity_on_melanoma_risk_in_a_family_sample_unselected_by_family_history_and_in_melanoma_prone_families_ L2 - https://academic.oup.com/jnci/article-lookup/doi/10.1093/jnci/djh136 DB - PRIME DP - Unbound Medicine ER -