p53 codon 72 Pro homozygosity increases the risk of cutaneous melanoma in individuals with dark skin complexion and among noncarriers of melanocortin 1 receptor red hair variants

Stefanaki, Irene; Stratigos, Alexander J.; Dimisianos, Gerasimos; Nikolaou, Vasiliki; Papadopoulos, Othon; Polydorou, Dorothea; Gogas, Helen; Tsoutsos, Dimosthenis; Panagiotou, P.; Kanavakis, Emmanuel; Antoniou, Christina; Katsambas, Andreas

doi:10.1111/j.1365-2133.2006.07645.x

Cited by 26 publications

(31 citation statements)

References 37 publications

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“…[12][13][14] In our study, we found no association with risk of CM when the genotypes of the two SNPs were combined. The effect of p53 Arg72Pro on melanoma remains controversial, with some studies reporting associations between melanoma and the PP genotype 17,19 and others reporting associations between melanoma and the RR genotype. 18,20 Moreover, here we report that the distribution of p53 Arg72Pro genotypes do not vary by age, gender or Breslow thickness.…”

Section: Discussionmentioning

confidence: 99%

“…The results have shown positive associations between the proline/proline (PP) genotype and disease risk for some tumor types (for example esophageal squamous cell carcinoma, lung cancer, renal cell carcinoma [12][13][14] but no association for other tumor types (for example colorectal cancer, breast cancer 15,16 ). The association between the p53 Arg72Pro polymorphism itself and melanoma risk is controversial, [17][18][19][20] with some studies showing associations between melanoma risk and the PP genotype, 17,19 but others showing increased melanoma risk with the arginine/arginine (RR) genotype. 18,20 In light of these findings, we examined the MDM2 SNP309 and p53 Arg72Pro genotypes to determine whether they could be linked to an increased CM susceptibility, age of cancer diagnosis and clinical pathological variables in an Italian population composed of women and men.…”

Section: Introductionmentioning

confidence: 99%

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MDM2 SNP309 and p53 Arg72Pro in cutaneous melanoma: association between SNP309 GG genotype and tumor Breslow thickness

et al. 2010

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A functional single nucleotide polymorphism (SNP) 309 T/G within mouse double minute 2 (MDM2) gene has been linked to onset and outcome of disease in tumors. Two published studies have shown discordant results regarding the effect of this SNP on age at diagnosis of cutaneous melanoma (CM) in Caucasian female populations. Here, we examined the age at diagnosis and clinical associations of CM with SNP309 and the related polymorphism, p53 Arg72Pro, in an Italian population (249 CM patients and 291 cancer-free controls) composed of women and men. MDM2 intronic region of 294 bp was directly sequenced, whereas Arg72Pro SNP was analyzed by polymerase chain reaction-restriction fragment length polymorphism. No associations were found among the SNP309, Arg72Pro, risk of CM, age at diagnosis and presence of metastasis in total subjects and when stratified according to the gender. The SNP309 was significantly associated with tumor Breslow thickness. The P-value in the minor allele recessive mode was 0.02, and the odds ratio (OR) adjusted for gender and age was 3.11 (95% confidential interval (CI)¼1.21-8.00). The SNP309 is not associated with the risk and age of onset of CM, and the presence of metastasis in an Italian population but the SNP309 GG may be a risk genotype for increasing in tumor Breslow thickness.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

MDM2 SNP309 and p53 Arg72Pro in cutaneous melanoma: association between SNP309 GG genotype and tumor Breslow thickness

et al. 2010

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“…The allelic variants exhibit distinct structural features and biological properties, with the codon 72 Pro being credited with a more efficient transcriptional activation and suppression of cell growth, and the arginine with a less efficient induction of apoptosis (Thomas et al, 1999). With regard to melanoma, two epidemiological studies reported an increased risk associated with the genotype Arg/Arg (Shen et al, 2003;Li et al, 2008), two studies found an association with the genotype Pro/Pro (Gwosdz et al, 2006;Stefanaki et al, 2007), and other studies found no effect with the development or progression of melanoma (Povey et al, 2007;Firoz et al, 2009). Some of the inconsistencies found across the different studies may be due to differences in sample size, study design, or characteristics of the study subjects.…”

Section: Introductionmentioning

confidence: 98%

Investigation of the Effect of MDM2 SNP309 and TP53 Arg72Pro Polymorphisms on the Age of Onset of Cutaneous Melanoma

Cotignola

Chou

Roy

et al. 2012

Journal of Investigative Dermatology

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Melanoma accounts for the majority of deaths from skin cancer. Women tend to be diagnosed at a younger age and have better survival than men. A tumor-host interaction might be responsible for these gender-specific differences. Recently, a functional single-nucleotide polymorphism in the promoter of the human homolog of mouse double minute 2 (MDM2) gene was characterized: single-nucleotide polymorphism (SNP)309 increases the MDM2 transcription. In melanoma, the effects for SNP309 and the related tumor protein p53 (TP53) Arg72Pro are inconsistent among published reports. This study investigated the association between SNP309 (RefSNP accession ID (rs)2279744) and TP53 codon 72 (rs1042522) polymorphisms, with outcome in a hospital-based cohort of 990 patients with melanoma. We assessed whether these polymorphisms were associated with clinicopathological and phenotypic characteristics and whether these SNPs affect the age of onset of the disease, recurrence, and survival. No significant associations were found between the SNPs and survival. However, women carrying the SNP309 GG genotype were less likely to be diagnosed at a younger age: odds ratio(adjusted<50) 0.52 (0.29-0.92). Our results suggest that women carrying the SNP309 GG genotype might be at lower risk of developing melanoma at a younger age compared with those carrying TG or TT. Further studies are needed to determine whether a nearby functional polymorphism is responsible for this effect in premenopausal women.

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“…In this regard, [44] showed that UV induction of the melanogenic ␣ -melanocyte-stimulating hormone ( ␣ -MSH) in skin is directly controlled by TP53 . Other studies have pointed to a relationship between the TP53 Arg72Pro polymorphism and susceptibility to different cancer types, including melanoma [6] , although this association however, has not gone unchallenged. Thus, a large association study found no association of Arg72Pro to six subtypes of cancer, including melanoma and non-melanoma skin cancer [12,45] .…”

Section: Exploring For Association To Melanoma Susceptibilitymentioning

confidence: 99%

“…Thus, an Arg72Pro non-synonymous polymorphism in TP53 (rs1042522) has been associated to susceptibility to human papillomavirus [4] , to skin cancer [5][6][7] or to breast cancer [8] among others, although these results have been challenged as inconsistent [9][10][11][12] . However, one of the largest association studies provides strong evidence for a dosedependent association of the 72Pro allele to increased longevity after diagnosis of any life-threatening disease [12] .…”

mentioning

confidence: 96%

The Diversity Profile of <i>TP53</i> Is Influenced by Positive Selection on the Immediately Upstream Locus<i> WDR79</i>

Alonso

Izagirre²,

López³

et al. 2009

Hum Hered

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Background/Aim:TP53 is an efficient central node in a signal transduction network that responds to minimize cancer. However, over 50% of tumors show some mutation in TP53. Thus, one might argue that this single central node network lacks robustness. Therefore, we wanted to investigate if natural selection has played a role in shaping the genomic region containing TP53. Methods: We have analyzed the HapMap data for evidence of selection using F_ST pairwise comparisons and the extended haplotype homozygosity test on a 200-kb region encompassing TP53. We have also resequenced 4 kb upstream TP53 in Europeans (including melanoma patients), Asians, Australian Aborigines and Africans. Results: Genetic hitchhiking by a linked, positively selected allele at the nearby gene WDR79 may be partly responsible for the sequence diversity profile of TP53. It can help explain why the TP53 Arg72 allele is the major allele in Europeans even when the alternative allele, 72Pro, has been reported to offer an increased longevity after disease. Conclusions: Despite the important role of TP53, a complex interplay with other evolutionary forces, which are extrinsic to TP53 function, may have driven the genetic diversity pattern of this locus, and, as a consequence, its structure and function.

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p53 codon 72 Pro homozygosity increases the risk of cutaneous melanoma in individuals with dark skin complexion and among noncarriers of melanocortin 1 receptor red hair variants

Abstract: p53 codon 72 Pro/Pro genotype could be a risk factor for the development of melanoma in the Greek population, especially in subgroups with darker skin pigmentation, as well as among noncarriers of the MC1R red hair polymorphic variants.

Cited by 26 publications

References 37 publications

MDM2 SNP309 and p53 Arg72Pro in cutaneous melanoma: association between SNP309 GG genotype and tumor Breslow thickness

MDM2 SNP309 and p53 Arg72Pro in cutaneous melanoma: association between SNP309 GG genotype and tumor Breslow thickness

Investigation of the Effect of MDM2 SNP309 and TP53 Arg72Pro Polymorphisms on the Age of Onset of Cutaneous Melanoma

The Diversity Profile of <i>TP53</i> Is Influenced by Positive Selection on the Immediately Upstream Locus<i> WDR79</i>

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