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Single Nucleotide Polymorphisms in Reactive Oxygen Species-related Genes in Melanoma Risk

  • Author(s): Liu-Smith, Feng
  • Advisor(s): Anton-Culver, Hoda
  • et al.
Abstract

Melanoma is the deadliest type of skin cancer. The major risk factor is UV radiation, which is tightly linked to UV-mediated generation of reactive oxygen species (ROS). ROS may be produced by mitochondria or by cellular enzyme system which includes NADPH Oxidases (NOX), superoxide dismutases (SODs) and catalase. This study genotyped age- and sex-matched case and control DNA samples and compared the allele frequency and genotype of 19 selected single nucleotide polymorphisms (SNPs) in the above genes. Seven SNPs exhibited significant different genotypes in cases and controls; ten of them (including the above 7) showed significant difference in a dominant model. All SNPs were further compared in case only within different variables (low or high exposure categories, skin features such as skin color, hair color, eye color and freckle numbers, sun exposure variables such as average annual sun hours, erythemal UV doses at birth, age 10, 30, 50 and 70, sun burns at age 10 and for life time, tumor characteristics such as Breslow depth and single/multiple tumors). Variants rs4998557 (SOD1), rs1049255 (CYBA) and rs2146521 (NOX4) repeatedly showed significant difference in these comparisons. Both rs4998557 and rs1049255 are associated with number of sun urns at age 10, which is a known risk factor for melanoma, hence these two variants may be important sun-burn related melanoma risk. These results may serve as a first step to provide information for precision prevention of melanoma.

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