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Genetically Predicted Serum Vitamin C Levels and Cutaneous Squamous Cell Carcinoma Risk

Published:November 04, 2022DOI:https://doi.org/10.1016/j.jid.2022.10.006
      Reactive oxygen species (ROS) are generated during oxidative metabolism and cellular response to external stressors and can potentiate keratinocyte carcinogenesis (
      • Ray P.D.
      • Huang B.
      • Tsuji Y.
      Reactive oxygen species (ROS) homeostatis and redox regulation in cellular signaling.
      ). ROS can be scavenged by antioxidants, including vitamin C. In vitro and in vivo studies have shown that vitamin C prevents oxidative damage to keratinocytes, which could help prevent the formation of cutaneous squamous cell carcinoma (cSCC) (
      • Kawashima S.
      • Funakoshi T.
      • Sato Y.
      • Saito N.
      • Ohsawa H.
      • Kurita K.
      • et al.
      Protective effect of pre- and post-vitamin C treatments on UVB-irradiation-induced skin damage.
      ,
      • Pauling L.
      • Willoughby R.
      • Reynolds R.
      • Blaisdell B.E.
      • Lawson S.
      Incidence of squamous cell carcinoma in hairless mice irradiated with ultraviolet light in relation to intake of ascorbic acid (vitamin C) and of D, L-alpha-tocopheryl acetate (vitamin E).
      ). However, epidemiologic studies have shown conflicting effects of vitamin C exposure on cSCC risk (
      • Asgari M.M.
      • Chren M.M.
      • Warton E.M.
      • Friedman G.D.
      • White E.
      Supplement use and risk of cutaneous squamous cell carcinoma.
      ,
      • Fung T.T.
      • Spiegelman D.
      • Egan K.M.
      • Giovannucci E.
      • Hunter D.J.
      • Willett W.C.
      Vitamin and carotenoid intake and risk of squamous cell carcinoma of the skin.
      ,
      • Hercberg S.
      • Ezzedine K.
      • Guinot C.
      • Preziosi P.
      • Galan P.
      • Bertrais S.
      • et al.
      Antioxidant supplementation increases the risk of skin cancers in women but not in men.
      ). Observational studies may have revealed conflicting results due to residual confounding. Thus, the association between serum vitamin C and cSCC risk needs further study with a method that minimizes the impact of residual confounding.

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