Association of MDM2 SNP309, age of onset, and gender in cutaneous melanoma

Elnaz F. Firoz, Melanie Warycha, Jan Zakrzewski, Danuta Pollens, Guimin Wang, Richard Shapiro, Russell Berman, Anna Pavlick, Prashiela Manga, Harry Ostrer, Julide Tok Celebi, Hideko Kamino, Farbod Darvishian, Linda Rolnitzky, Judith D. Goldberg, Iman Osman, David Polsky

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Purpose: In certain cancers, MDM2 SNP309 has been associated with early tumor onset in women. In melanoma, incidence rates are higher in women than in men among individuals less than 40 years of age, but among those older than 50 years of age, melanoma is more frequent in men than in women. To investigate this difference, we examined the association among MDM2 SNP309, age at diagnosis, and gender among melanoma patients. Experimental Design: Prospectively enrolled melanoma patients (N = 227) were evaluated for MDM2 SNP309 and the related polymorphism, p53 Arg72Pro. DNAwas isolated from patient blood samples, and genotypes were analyzed by PCR-restriction fragment length polymorphism. Associations among MDM2 SNP309, p53 Arg72Pro, age at diagnosis, and clinicopathologic features of melanoma were analyzed. Results: The median age at diagnosis was 13 years earlier among women with a SNP309 GG genotype (46 years) compared with women with TG+TT genotypes (59 years; P = 0.19). Analyses using age dichotomized at each decade indicated that women with a GG genotype had significantly higher risks of being diagnosed with melanoma at ages <50 years compared with women ≥50 years, but not when the comparison was made between women <60 and ≥60 years. At ages <50 years, women with a GG genotype had a 3.89 times greater chance of being diagnosed compared with women with TG+TT genotypes (P = 0.01). Similar observations were not seen among men. Conclusions: Our data suggest that MDM2 may play an important role in the development of melanoma in women. The MDM2 SNP309 genotype may help identify women at risk of developing melanoma at a young age.

Original languageEnglish (US)
Pages (from-to)2573-2580
Number of pages8
JournalClinical Cancer Research
Volume15
Issue number7
DOIs
StatePublished - Apr 1 2009
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Firoz, E. F., Warycha, M., Zakrzewski, J., Pollens, D., Wang, G., Shapiro, R., Berman, R., Pavlick, A., Manga, P., Ostrer, H., Celebi, J. T., Kamino, H., Darvishian, F., Rolnitzky, L., Goldberg, J. D., Osman, I., & Polsky, D. (2009). Association of MDM2 SNP309, age of onset, and gender in cutaneous melanoma. Clinical Cancer Research, 15(7), 2573-2580. https://doi.org/10.1158/1078-0432.CCR-08-2678