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


METHODS
Prospectively enrolled melanoma patients (N = 227) were evaluated for MDM2 SNP309 and the related polymorphism, p53 Arg72Pro. DNA was 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 >or=50 years, but not when the comparison was made between women <60 and >or=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.
Firoz
Elnaz F
EF
Department of Dermatology, New York University School of Medicine, New York, New York, USA.
Warycha
Melanie
M
Zakrzewski
Jan
J
Pollens
Danuta
D
Wang
Guimin
G
Shapiro
Richard
R
Berman
Russell
R
Pavlick
Anna
A
Manga
Prashiela
P
Ostrer
Harry
H
Celebi
Julide Tok
JT
Kamino
Hideko
H
Darvishian
Farbod
F
Rolnitzky
Linda
L
Goldberg
Judith D
JD
Osman
Iman
I
Polsky
David
D