Current research on UV-induced DNA damage and its role in promoting the development of skin malignancies

doi:10.3969/j.issn.1674-8115.2025.02.012

Abstract

Abstract:

Skin malignancies include non-melanoma skin cancers and melanoma, with high incidence rates that pose a significant burden on public health and healthcare systems. Research in this area is crucial. Ultraviolet radiation (UV) is recognized as the primary risk factor for skin malignancies, with its main carcinogenic mechanism involving UV-induced DNA damage, which leads to the accumulation of mutations in key oncogenes and tumor suppressor genes. This accumulation promotes malignant transformation of related cells, ultimately resulting in the formation of malignant tumors. Understanding the specific processes through which UV-induced DNA damage contributes to the development of skin malignancies is crucial for advancing related research. Therefore, this paper focuses on the mechanisms of UV-induced DNA damage, the repair mechanisms for UV-induced DNA damage, and the relationship between UV-induced DNA damage and the occurrence of the three major types of skin malignancies.

Key words: skin malignant tumor, ultraviolet rays, DNA damage

CLC Number:

R739.5

ZHANG Boyuan, YAO Zhirong. Current research on UV-induced DNA damage and its role in promoting the development of skin malignancies[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2025, 45(2): 228-232.

TrendMD

References 60

1	NEHAL K S, BICHAKJIAN C K. Update on keratinocyte carcinomas[J]. N Engl J Med, 2018, 379(4): 363-374.
2	KARIA P S, HAN J L, SCHMULTS C D. Cutaneous squamous cell carcinoma: estimated incidence of disease, nodal metastasis, and deaths from disease in the United States, 2012[J]. J Am Acad Dermatol, 2013, 68(6): 957-966.
3	LOMAS A, LEONARDI-BEE J, BATH-HEXTALL F. A systematic review of worldwide incidence of nonmelanoma skin cancer[J]. Br J Dermatol, 2012, 166(5): 1069-1080.
4	WU W, WEINSTOCK M A. Trends of keratinocyte carcinoma mortality rates in the United States as reported on death certificates, 1999 through 2010[J]. Dermatol Surg, 2014, 40(12): 1395-1401.
5	SCHADENDORF D, FISHER D E, GARBE C, et al. Melanoma[J]. Nat Rev Dis Primers, 2015, 1: 15003.
6	URBAN K, MEHRMAL S, UPPAL P, et al. The global burden of skin cancer: a longitudinal analysis from the Global Burden of Disease Study, 1990-2017[J]. JAAD Int, 2021, 2: 98-108.
7	徐莉莉, 张丽成, 田雪, 等. 中国皮肤癌住院患者流行病学的研究[J]. 中国循证医学杂志, 2020, 20(11): 1280-1283.
	XU L L, ZHANG L C, TIAN X, et al. Epidemiological research on inpatients with skin cancer in China[J]. Chinese Journal of Evidence-based Medicine, 2020, 20(11):1280-1283
8	XIANG F, LUCAS R, HALES S, et al. Incidence of nonmelanoma skin cancer in relation to ambient UV radiation in white populations, 1978-2012: empirical relationships[J]. JAMA Dermatol, 2014, 150(10): 1063-1071.
9	DE VRIES E, TRAKATELLI M, KALABALIKIS D, et al. Known and potential new risk factors for skin cancer in European populations: a multicentre case-control study[J]. Br J Dermatol, 2012, 167(Suppl 2): 1-13.
10	GARRETT G L, BLANC P D, BOSCARDIN J, et al. Incidence of and risk factors for skin cancer in organ transplant recipients in the United States[J]. JAMA Dermatol, 2017, 153(3): 296-303.
11	WANG J, ALDABAGH B, YU J, et al. Role of human papillomavirus in cutaneous squamous cell carcinoma: a meta-analysis[J]. J Am Acad Dermatol, 2014, 70(4): 621-629.
12	EUVRARD S, MORELON E, ROSTAING L, et al. Sirolimus and secondary skin-cancer prevention in kidney transplantation[J]. N Engl J Med, 2012, 367(4): 329-339.
13	WU X W, NGUYEN B C, DZIUNYCZ P, et al. Opposing roles for calcineurin and ATF3 in squamous skin cancer[J]. Nature, 2010, 465(7296): 368-372.
14	O'DONOVAN P, PERRETT C M, ZHANG X H, et al. Azathioprine and UVA light generate mutagenic oxidative DNA damage[J]. Science, 2005, 309(5742): 1871-1874.
15	SHIMIZU Y, NAKATSURU Y, ICHINOSE M, et al. Benzo [a] Pyrene carcinogenicity is lost in mice lacking the aryl hydrocarbon receptor[J]. Proc Natl Acad Sci U S A, 2000, 97(2): 779-782.
16	EL GHISSASSI F, BAAN R, STRAIF K, et al. A review of human carcinogens: part D: radiation[J]. Lancet Oncol, 2009, 10(8): 751-752.
17	NADHAN K S, CHUNG C L, BUCHANAN E M, et al. Risk factors for keratinocyte carcinoma skin cancer in nonwhite individuals: a retrospective analysis[J]. J Am Acad Dermatol, 2019, 81(2): 373-378.
18	ANDERSON R R, PARRISH J A. The optics of human skin[J]. J Invest Dermatol, 1981, 77(1): 13-19.
19	BRULS W A, SLAPER H, VAN DER LEUN J C, et al. Transmission of human epidermis and stratum corneum as a function of thickness in the ultraviolet and visible wavelengths[J]. Photochem Photobiol, 1984, 40(4): 485-494.
20	SINHA R P, HÄDER D P. UV-induced DNA damage and repair: a review[J]. Photochem Photobiol Sci, 2002, 1(4): 225-236.
21	YOUNG A R, CHADWICK C A, HARRISON G I, et al. The similarity of action spectra for thymine dimers in human epidermis and erythema suggests that DNA is the chromophore for erythema[J]. J Invest Dermatol, 1998, 111(6): 982-988.
22	CADET J, SAGE E, DOUKI T. Ultraviolet radiation-mediated damage to cellular DNA[J]. Mutat Res, 2005, 571(1/2): 3-17.
23	RÜNGER T M, KAPPES U P. Mechanisms of mutation formation with long-wave ultraviolet light (UVA)[J]. Photodermatol Photoimmunol Photomed, 2008, 24(1): 2-10.
24	BACHELOR M A, BOWDEN G T. UVA-mediated activation of signaling pathways involved in skin tumor promotion and progression[J]. Semin Cancer Biol, 2004, 14(2): 131-138.
25	PAOLO DOTTO G, RUSTGI A K. Squamous cell cancers: a unified perspective on biology and genetics[J]. Cancer Cell, 2016, 29(5): 622-637.
26	SONG K, MOHSENI M, TAGHIPOUR F. Mechanisms investigation on bacterial inactivation through combinations of UV wavelengths[J]. Water Res, 2019, 163: 114875.
27	FRIEDBERG E C. A brief history of the DNA repair field[J]. Cell Res, 2008, 18(1): 3-7.
28	SANCAR A. Mechanisms of DNA repair by photolyase and excision nuclease (Nobel lecture)[J]. Angew Chem Int Ed, 2016, 55(30): 8502-8527.
29	SPIVAK G. Nucleotide excision repair in humans[J]. DNA Repair (Amst), 2015, 36: 13-18.
30	DIANOV G L, HÜBSCHER U. Mammalian base excision repair: the forgotten archangel[J]. Nucleic Acids Res, 2013, 41(6): 3483-3490.
31	WIKONKAL N M, BRASH D E. Ultraviolet radiation induced signature mutations in photocarcinogenesis[J]. J Investig Dermatol Symp Proc, 1999, 4(1): 6-10.
32	NARAYANAN D L, SALADI R N, FOX J L. Ultraviolet radiation and skin cancer[J]. Int J Dermatol, 2010, 49(9): 978-986.
33	D'ORAZIO J, JARRETT S, AMARO-ORTIZ A, et al. UV radiation and the skin[J]. Int J Mol Sci, 2013, 14(6): 12222-12248.
34	VERKOUTEREN J C, RAMDAS K R, WAKKEE M, et al. Epidemiology of basal cell carcinoma: scholarly review[J]. Br J Dermatol, 2017, 177(2): 359-372.
35	BRASH D E, RUDOLPH J A, SIMON J A, et al. A role for sunlight in skin cancer: uv-induced p53 mutations in squamous cell carcinoma[J]. Proc Natl Acad Sci USA, 1991, 88(22): 10124-10128.
36	OUHTIT A, NAKAZAWA H, ARMSTRONG B K, et al. UV-radiation-specific p53 mutation frequency in normal skin as a predictor of risk of basal cell carcinoma[J]. J Natl Cancer Inst, 1998, 90(7): 523-531.
37	RASS K, REICHRATH J. UV damage and DNA repair in malignant melanoma and nonmelanoma skin cancer[J]. Adv Exp Med Biol, 2008, 624: 162-178.
38	LANE D P. p53, guardian of the genome[J]. Nature, 1992, 358(6381): 15-16.
39	VALLINI G, CALABRESE L, CANINO C, et al. Signaling pathways and therapeutic strategies in advanced basal cell carcinoma[J]. Cells, 2023, 12(21): 2534.
40	BLANPAIN C, FUCHS E. Epidermal homeostasis: a balancing act of stem cells in the skin[J]. Nat Rev Mol Cell Biol, 2009, 10(3): 207-217.
41	STACEY S N, SULEM P, MASSON G, et al. New common variants affecting susceptibility to basal cell carcinoma[J]. Nat Genet, 2009, 41(8): 909-914.
42	FARTASCH M, DIEPGEN T L, SCHMITT J, et al. The relationship between occupational Sun exposure and non-melanoma skin cancer: clinical basics, epidemiology, occupational disease evaluation, and prevention[J]. Dtsch Arztebl Int, 2012, 109(43): 715-720.
43	JOHN S M, TRAKATELLI M, ULRICH C. Non-melanoma skin cancer by solar UV: the neglected occupational threat[J]. J Eur Acad Dermatol Venereol, 2016, 30(Suppl 3): 3-4.
44	ZIEGLER A, JONASON A S, LEFFELL D J, et al. Sunburn and p53 in the onset of skin cancer[J]. Nature, 1994, 372(6508): 773-776.
45	REICHRATH J, RASS K. Ultraviolet damage, DNA repair and vitamin D in nonmelanoma skin cancer and in malignant melanoma: an update[J]. Adv Exp Med Biol, 2014, 810: 208-233.
46	SÁNCHEZ-DANÉS A, BLANPAIN C. Deciphering the cells of origin of squamous cell carcinomas[J]. Nat Rev Cancer, 2018, 18(9): 549-561.
47	JONASON A S, KUNALA S, PRICE G J, et al. Frequent clones of p53-mutated keratinocytes in normal human skin[J]. Proc Natl Acad Sci USA, 1996, 93(24): 14025-14029.
48	SOUTH A P, PURDIE K J, WATT S A, et al. NOTCH1 mutations occur early during cutaneous squamous cell carcinogenesis[J]. J Invest Dermatol, 2014, 134(10): 2630-2638.
49	WANG N J, SANBORN Z, ARNETT K L, et al. Loss-of-function mutations in Notch receptors in cutaneous and lung squamous cell carcinoma[J]. Proc Natl Acad Sci USA, 2011, 108(43): 17761-17766.
50	LEE C S, BHADURI A, MAH A, et al. Recurrent point mutations in the kinetochore gene KNSTRN in cutaneous squamous cell carcinoma[J]. Nat Genet, 2014, 46(10): 1060-1062.
51	SCHADENDORF D, VAN AKKOOI A C J, BERKING C, et al. Melanoma[J]. Lancet, 2018, 392(10151): 971-984.
52	GANDINI S, SERA F, CATTARUZZA M S, et al. Meta-analysis of risk factors for cutaneous melanoma: ii. Sun exposure[J]. Eur J Cancer, 2005, 41(1): 45-60.
53	SHUSTER S. Is sun exposure a major cause of melanoma? No[J]. BMJ, 2008, 337: a764.
54	MENZIES S W. Is Sun exposure a major cause of melanoma? Yes[J]. BMJ, 2008, 337: a763.
55	HODIS E, WATSON I R, KRYUKOV G V, et al. A landscape of driver mutations in melanoma[J]. Cell, 2012, 150(2): 251-263.
56	ALEXANDROV L B, NIK-ZAINAL S, WEDGE D C, et al. Signatures of mutational processes in human cancer[J]. Nature, 2013, 500(7463): 415-421.
57	VIROS A, SANCHEZ-LAORDEN B, PEDERSEN M, et al. Ultraviolet radiation accelerates BRAF-driven melanomagenesis by targeting TP53[J]. Nature, 2014, 511(7510): 478-482.
58	GUIDA S, GUIDA G, GODING C R. MC1R functions, expression, and implications for targeted therapy[J]. J Invest Dermatol, 2022, 142(2): 293-302.e1.
59	KRAUTHAMMER M, KONG Y, HA B H, et al. Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma[J]. Nat Genet, 2012, 44(9): 1006-1014.
60	BERGER M F, HODIS E, HEFFERNAN T P, et al. Melanoma genome sequencing reveals frequent PREX2 mutations[J]. Nature, 2012, 485(7399): 502-506.

[1]	SHI Zelun, WANG Qing, HE Wen, FU Weijia, WANG Yingwen, HAN Xiao, ZHANG Xiaobo. Nanoplastics aggravate severe asthma by inducing DNA damage of alveolar type Ⅱ epithelial cells [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2024, 44(11): 1391-1405.
[2]	WANG Renjie, HUA Hui, ZHU ChaoYu, WEI Li. Advances of GADD45b in hepatic glucose and lipid metabolism [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2024, 44(10): 1316-1322.
[3]	Wei LIU, Min-wen ZHU, Lan WU. Array detection and expression verification of DNA damage repair related genes in oral leukoplakia cancerization [J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2021, 41(3): 302-307.
[4]	MU Hua-qiao, LUO Xin, QI Hong-bo, LIU Xi-ru. Effects of Gadd45α-knockdown on human extravillous trophoblast cell migration and invasion functions under hypoxia/re-oxygenation [J]. , 2017, 37(3): 293-.
[5]	WU Hong-juan, CHEN Yu, ZHAO Qi, et al. Effect of melatonin on acrylamide-induced DNA damage in rat testicular cells [J]. , 2012, 32(8): 1038-.
[6]	WANG Hong-xiang, CHEN Bin, HU Kai, et al. Correlation analysis between epididymal sperm DNA damage and outcome of intracytoplasmic sperm injection in patients with obstructive azoospermia [J]. , 2012, 32(8): 983-.
[7]	LIU Xiu-ling, WANG Li, JIANG Chun-hua, et al. Effects of thiamine and riboflavin on H₂O₂-induced DNA oxidative damage [J]. , 2009, 29(9): 1049-.