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MC1R, ASIP, and DNA repair in sporadic and familial melanoma in a Mediterranean population.
J Natl Cancer Inst 2005; 97(13):998-1007JNCI

Abstract

BACKGROUND

Melanoma risk factors include fair pigmentation, multiple nevi, low DNA repair capacity, and CDKN2A or CDK4 mutations. Variants of the melanocortin-1 receptor (MC1R) gene have been associated with fair pigmentation and melanoma risk, and a polymorphism of the Agouti Signaling Protein (ASIP) gene has been associated with dark pigmentation. We examined MC1R and ASIP genotypes in relation to phenotypic characteristics, sporadic and familial melanoma risk, and melanoma thickness as an indicator of disease progression in a Mediterranean population.

METHODS

We studied 267 melanoma patients and 382 control subjects from a case-control study and a family study in northeastern Italy. Host factors were assessed by physical examination, questionnaire, spectrophotometer, and minimal erythema dose measurement. MC1R was sequenced, ASIP was genotyped, and DNA repair capacity was measured by the host-cell reactivation assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression models. Effect modification of the association between MC1R and melanoma risk by phenotypic characteristics and DNA repair capacity was also assessed. All statistical tests were two-sided.

RESULTS

Carrying MC1R variant alleles was associated with a two- to fourfold increase in risk of both sporadic and familial melanoma compared with carrying wild-type MC1R, particularly in individuals carrying multiple variant alleles (OR = 3.9; 95% CI = 3.3 to 4.6). This association was stronger in individuals with fewer additional risk factors (those with dark skin or few nevi). MC1R variant allele carriers were also three to four times more likely than were non-carriers to have thick melanomas. The ASIP polymorphism was not associated with pigmentation, nevi, or melanoma risk.

CONCLUSIONS

MC1R was associated with melanoma risk and progression in a Mediterranean population, particularly in the absence of other strong risk factors, such as freckling or many nevi.

Authors+Show Affiliations

Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD 20892-7236, USA. landim@mail.nih.govNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15998953

Citation

Landi, Maria Teresa, et al. "MC1R, ASIP, and DNA Repair in Sporadic and Familial Melanoma in a Mediterranean Population." Journal of the National Cancer Institute, vol. 97, no. 13, 2005, pp. 998-1007.
Landi MT, Kanetsky PA, Tsang S, et al. MC1R, ASIP, and DNA repair in sporadic and familial melanoma in a Mediterranean population. J Natl Cancer Inst. 2005;97(13):998-1007.
Landi, M. T., Kanetsky, P. A., Tsang, S., Gold, B., Munroe, D., Rebbeck, T., ... Pfeiffer, R. M. (2005). MC1R, ASIP, and DNA repair in sporadic and familial melanoma in a Mediterranean population. Journal of the National Cancer Institute, 97(13), pp. 998-1007.
Landi MT, et al. MC1R, ASIP, and DNA Repair in Sporadic and Familial Melanoma in a Mediterranean Population. J Natl Cancer Inst. 2005 Jul 6;97(13):998-1007. PubMed PMID: 15998953.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MC1R, ASIP, and DNA repair in sporadic and familial melanoma in a Mediterranean population. AU - Landi,Maria Teresa, AU - Kanetsky,Peter A, AU - Tsang,Shirley, AU - Gold,Bert, AU - Munroe,David, AU - Rebbeck,Timothy, AU - Swoyer,Jennifer, AU - Ter-Minassian,Monica, AU - Hedayati,Mohammad, AU - Grossman,Lawrence, AU - Goldstein,Alisa M, AU - Calista,Donato, AU - Pfeiffer,Ruth M, PY - 2005/7/7/pubmed PY - 2005/7/9/medline PY - 2005/7/7/entrez SP - 998 EP - 1007 JF - Journal of the National Cancer Institute JO - J. Natl. Cancer Inst. VL - 97 IS - 13 N2 - BACKGROUND: Melanoma risk factors include fair pigmentation, multiple nevi, low DNA repair capacity, and CDKN2A or CDK4 mutations. Variants of the melanocortin-1 receptor (MC1R) gene have been associated with fair pigmentation and melanoma risk, and a polymorphism of the Agouti Signaling Protein (ASIP) gene has been associated with dark pigmentation. We examined MC1R and ASIP genotypes in relation to phenotypic characteristics, sporadic and familial melanoma risk, and melanoma thickness as an indicator of disease progression in a Mediterranean population. METHODS: We studied 267 melanoma patients and 382 control subjects from a case-control study and a family study in northeastern Italy. Host factors were assessed by physical examination, questionnaire, spectrophotometer, and minimal erythema dose measurement. MC1R was sequenced, ASIP was genotyped, and DNA repair capacity was measured by the host-cell reactivation assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression models. Effect modification of the association between MC1R and melanoma risk by phenotypic characteristics and DNA repair capacity was also assessed. All statistical tests were two-sided. RESULTS: Carrying MC1R variant alleles was associated with a two- to fourfold increase in risk of both sporadic and familial melanoma compared with carrying wild-type MC1R, particularly in individuals carrying multiple variant alleles (OR = 3.9; 95% CI = 3.3 to 4.6). This association was stronger in individuals with fewer additional risk factors (those with dark skin or few nevi). MC1R variant allele carriers were also three to four times more likely than were non-carriers to have thick melanomas. The ASIP polymorphism was not associated with pigmentation, nevi, or melanoma risk. CONCLUSIONS: MC1R was associated with melanoma risk and progression in a Mediterranean population, particularly in the absence of other strong risk factors, such as freckling or many nevi. SN - 1460-2105 UR - https://www.unboundmedicine.com/medline/citation/15998953/MC1R_ASIP_and_DNA_repair_in_sporadic_and_familial_melanoma_in_a_Mediterranean_population_ L2 - https://academic.oup.com/jnci/article-lookup/doi/10.1093/jnci/dji176 DB - PRIME DP - Unbound Medicine ER -