The lack of E318K MITF germline mutation in Latvian melanoma patients

Cancer risks associated with the germline MITF(E318K) variant

“…Studies were conducted on a mixture of hereditary and sporadic melanoma populations. A few studies identified a relationship of this variant with renal cell carcinoma (RCC), pancreatic cancer, and pheochromocytoma/paraganglioma 2,4,10 . Bertolotto et al identified over a fivefold increased risk for carriers to develop RCC, melanoma, or both cancers in 829 patients (OR 5.55; 95% CI 2.59-12.91; p = 1.2E−6) and identified a fivefold risk of developing RCC only in 164 "genetically-enriched" patients who were wild-type for RCC-predisposing genes (OR 5.19; 95% CI 1.37-16.87; p = 0.008) 2 .…”

“…Meta-analysis of the data compiled from nine published studies (n = 331) 1 – 10 demonstrated that the variant was significantly correlated with melanoma (Fig. 1 ; odds ratio (OR) 2.37; 95% confidence interval (CI) 1.89–2.97; p < 1E−5; I 2= 19%).…”

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Figure 1 Meta-analysis Odds Ratio of the Association Between MITF(E318K) and Personal History of Melanoma. 1 Ozola et al also studied relationship of MITF(E318K) with melanoma, but found no variants in cases or controls and thus was not included in calculations 10 .

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“…A rare functional variant of MITF(E318K) has been shown to disrupt a conserved SUMOylation site and to confer a two-to fourfold risk for cutaneous melanoma 1,2 . Moreover, there have been small studies suggesting that this variant is also associated with other cancers such as renal cell carcinoma (RCC) [1][2][3][4][5][6][7][8][9][10][11][12][13] . However, since epidemiologic observations have documented an association between cutaneous melanoma and many other malignancies, including RCC, it is possible that MITF(E318K) represents a germline "passenger" mutation in these other cancers without directly impacting the risk of these other cancers such as RCC.…”