Prediction of Melanoma Risk in a Southern European Population Based on a Weighted Genetic Risk Score

Kypreou, Katerina P.; Stefanaki, Irene; Antonopoulou, Kyriaki; Karagianni, Fani; Ntritsos, Georgios; Zaras, Alexios; Nikolaou, Vasiliki; Kalfa, Iro; Chasapi, Vasiliki; Polydorou, Dorothea; Gogas, Helen; Spyrou, George M.; Bertram, Lars; Lill, Christina M.; Ioannidis, John P. A.; Antoniou, Christina; Εvangelou, Εvangelos; Stratigos, Alexander

doi:10.1016/j.jid.2015.12.007

Cited by 26 publications

(27 citation statements)

References 45 publications

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“…A second population‐based study from Greece found a PRS of 26 GWAS‐identified SNVs was associated with a modest increase in discriminative ability between models containing only phenotypic risk factors (age, sex, eye/hair/skin colour, phototype and tanning ability) and phenotypic factors plus PRS (phenotypic model: AUC 0·764, 95% CI 0·741–0·787; phenotypic model + PRS: AUC 0·775, 95% CI 0·752–0·797) . This study was limited by a relatively small sample size as well as lack of family history and other known melanoma risk factors.…”

Section: Resultsmentioning

confidence: 92%

Genome‐wide association studies and polygenic risk scores for skin cancer: clinically useful yet?

Roberts

Asgari

Toland³

2019

Br J Dermatol

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Summary Background Genome‐wide association studies (GWAS) have identified thousands of susceptibility variants, although most have been associated with small individual risk estimates that offer little predictive value. However, combining multiple variants into polygenic risk scores (PRS) may be more informative. Multiple studies have developed PRS composed of GWAS‐identified variants for cutaneous cancers. This review highlights data from these studies. Objectives To review published GWAS and PRS studies for melanoma, cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC), and discuss their potential clinical utility. Methods We searched PubMed and the National Human Genome Research Institute–European Bioinformatics Institute GWAS catalogue to identify relevant studies. Results Results from 21 GWAS (11 melanoma, 3 cSCC, 7 BCC) and 11 PRS studies are summarized. Six loci in pigmentation genes overlap between these three cancers (ASIP/RALY, IRF4, MC1R, OCA2, SLC45A2 and TYR). Additional loci overlap for cSCC/BCC and BCC/melanoma, but no other loci are shared between cSCC and melanoma. PRS for melanoma show roughly two‐to‐threefold increases in risk and modest improvements in risk prediction (2–7% increases). PRS are associated with twofold and threefold increases in risk of cSCC and BCC, respectively, with small improvements (2% increase) in predictive ability. Conclusions Existing data indicate that PRS may offer small, but potentially meaningful, improvements to risk prediction. Additional research is needed to clarify the potential utility of PRS in cutaneous carcinomas. Clinical translation will require well‐powered validation studies incorporating known risk factors to evaluate PRS as tools for screening. What's already known about this topic? Over 50 susceptibility loci for melanoma, basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) have been identified in genome‐wide association studies (GWAS). Polygenic risk scores (PRS) using variants identified from GWAS have also been developed for melanoma, BCC and cSCC, and investigated with respect to clinical risk prediction. What does this study add? This review provides an overview of GWAS findings and the potential clinical utility of PRS for melanoma, BCC and cSCC.

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Section: Resultsmentioning

confidence: 92%

Genome‐wide association studies and polygenic risk scores for skin cancer: clinically useful yet?

Roberts

Asgari

Toland³

2019

Br J Dermatol

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“…The progress of molecular studies has shown that solar ultraviolet (UV) radiation is an important environmental risk factor for the development of melanoma 3,13,15,18 . It has been shown that the risk varies depending on geographical location, type of skin, hair color, number of nevi and family history of melanoma 3,18,19 .…”

Section: Introductionmentioning

confidence: 99%

Melanoma: clinical-pathological and molecular analysis in patients of Ibague city, Colombia

Puentes

Estrada

Bohórquez

et al. 2020

Duazary

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This study aimed to establish the clinicopathological characteristics of patients with melanoma and its association with BRAF gene mutations. The pathology reports and paraffin-embedded tumor samples from 47 women and 30 men with melanoma, with an average age of diagnosis of 60 years, were reviewed at the Hospital Federico Lleras Acosta of Ibague, between 2010 and 2016. The presence of V600E mutation at the exon 15 of BRAF gene, was analyzed in these tumoral samples by Sanger sequencing and visual inspection of the electropherograms. We also studied the clinicopathological variables with X2, t-Student and the Kaplan Meier index. Most of the lesions were located in the lower limbs (46.6%). The most frequent subtype was Acral Lentiginous Melanoma (41.8%). Most lesions were of poor prognosis: Breslow depth greater than 4.1 mm (52.7%), ulceration (61.4%) and medium or high mitotic rate (> 30 %). The V600E mutation was identified in five patients with large, deep and ulcerated tumors, four of them had less than four years of survival. In conclusion, there was a higher frequency of melanoma in women, V600E BRAF mutation was present in patients with advanced disease (high Breslow index) and, the probability of five-year survival was less than 40%.

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“…The discovery of susceptibility variants for human complex traits through genome-wide association studies (GWASs) has facilitated the potential application of genetic risk models, which could guide clinical professionals in their decision making by estimating an individual’s probability of having a special disease [ 10 – 13 ]. For leprosy, it has become increasingly apparent that, besides exposure to M .…”

Section: Introductionmentioning

confidence: 99%

Prediction of leprosy in the Chinese population based on a weighted genetic risk score

Wang

et al. 2018

PLoS Negl Trop Dis

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Genome wide association studies (GWASs) have revealed multiple genetic variants associated with leprosy in the Chinese population. The aim of our study was to utilize the genetic variants to construct a risk prediction model through a weighted genetic risk score (GRS) in a Chinese set and to further assess the performance of the model in identifying higher-risk contact individuals in an independent set. The highest prediction accuracy, with an area under the curve (AUC) of 0.743 (95% confidence interval (CI): 0.729–0.757), was achieved with a GRS encompassing 25 GWAS variants in a discovery set that included 2,144 people affected by leprosy and 2,671 controls. Individuals in the high-risk group, based on genetic factors (GRS > 28.06), have a 24.65 higher odds ratio (OR) for developing leprosy relative to those in the low-risk group (GRS≤18.17). The model was then applied to a validation set consisting of 1,385 people affected by leprosy and 7,541 individuals in contact with leprosy, which yielded a discriminatory ability with an AUC of 0.707 (95% CI: 0.691–0.723). When a GRS cut-off value of 22.38 was selected with the optimal sensitivity and specificity, it was found that 39.31% of high risk contact individuals should be screened in order to detect leprosy in 64.9% of those people affected by leprosy. In summary, we developed and validated a risk model for the prediction of leprosy that showed good discrimination capabilities, which may help physicians in the identification of patients coming into contact with leprosy and are at a higher-risk of developing this condition.

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Prediction of Melanoma Risk in a Southern European Population Based on a Weighted Genetic Risk Score

Cited by 26 publications

References 45 publications

Genome‐wide association studies and polygenic risk scores for skin cancer: clinically useful yet?

Genome‐wide association studies and polygenic risk scores for skin cancer: clinically useful yet?

Melanoma: clinical-pathological and molecular analysis in patients of Ibague city, Colombia

Prediction of leprosy in the Chinese population based on a weighted genetic risk score

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