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

ABSTRACT: 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.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.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.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.

SUBMITTER: Firoz EF

PROVIDER: S-EPMC3881546 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature

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

Firoz Elnaz F EF 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

Clinical cancer research : an official journal of the American Association for Cancer Research 20090324 7

<h4>Purpose</h4>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.<h4>Experimental design</h4>Prospectively enrolled melanoma patients ...[more]

PMID: 19318491

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Project description:BACKGROUND:Murine double minute 2 homolog (MDM2) plays an important role in the downregulation of P53 tumor suppressor gene. MDM2 inhibits P53 transcriptional activity and thereby results in accelerated tumor formation. Overexpression of MDM2 has been found in several cancer types including endometrial cancer. SNP309 is located in the promoter region of MDM2 and contributes to the overexpression of MDM2. The association between MDM2 SNP309 polymorphism and endometrial cancer risk has been investigated in several studies; however, the conclusion remains controversial. OBJECTIVES:We performed the present meta-analysis to give a comprehensive conclusion of the association between MDM2 SNP309 polymorphism and endometrial cancer susceptibility. METHODS:We conducted a literature research on PubMed, Embase, Cochrane Library, OVID, Web of Science, Wan Fang, CNKI, and CQVIP databases up to July 31, 2018. Newcastle-Ottawa scale was used to assess the quality of studies. We evaluated the strength of association by combining odds ratios (ORs) and 95% confidence intervals (CIs) in 5 different genetic models under a fixed-effect model or random-effect model. We further conducted subgroup analysis by ethnicity, source of control, histological type, clinical type, grade, and stage of tumor. Sensitivity analysis and publication bias were also performed. RESULTS:Nine eligible studies were finally included in our meta-analysis. We found MDM2 SNP309 polymorphism increased the risk of endometrial cancer under allele model (OR: 1.23, 95% CI: 1.06-1.41, P?=?.005), homozygote model (OR: 1.43, 95% CI: 1.13-1.81, P?=?.003) and recessive model (OR: 1.55, 95% CI: 1.17-2.04, P?=?.002). Subgroup analysis suggested a similar elevated risk in both Asians and Caucasians. We identified a strong association of enhanced susceptibility to endometrial cancer in endometrioid group (OR: 2.13, 95% CI: 1.28-3.54, P?=?.004) and Type I group (OR: 1.89, 95% CI: 1.25-2.86, P?=?.002) under dominant model. We identified no significant publication bias according to Egger's test. CONCLUSIONS:Our meta-analysis suggested that MDM2 SNP309 polymorphism increased the risk of endometrial cancer significantly, especially in endometrioid and Type I endometrial cancer, indicating MDM2 could serve as a potential diagnostic factor marker for endometrial cancer.

Dataset Information

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

Publications

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

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