From the Guidelines
UV radiation causes cancer primarily by damaging DNA in skin cells through the formation of cyclobutane pyrimidine dimers and 6-4 photoproducts, leading to mutations in genes that regulate cell growth and division. When UV rays, especially UVB and UVC wavelengths, penetrate the skin, they are absorbed by DNA molecules, creating abnormal chemical bonds between adjacent thymine bases, forming these structures 1. These DNA lesions distort the DNA helix, potentially leading to mutations during cell replication if not properly repaired. While cells have natural repair mechanisms like nucleotide excision repair to fix this damage, repeated UV exposure can overwhelm these systems, allowing mutations to accumulate in genes that regulate cell growth and division, particularly tumor suppressor genes like p53. Some key points to consider include:
- UV radiation exposure during childhood and youth is linked to a moderately increased risk for skin cancer later in life, as found by the USPSTF 1
- UV radiation exposure in adults is linked to a small increase in risk for skin cancer, with epidemiologic evidence supporting this association 1
- Certain populations, such as those with fair skin, light hair and eye color, or freckles, are at increased risk for skin cancer and should take extra precautions to minimize UV exposure 1 Additionally, UV radiation generates reactive oxygen species that cause oxidative damage to DNA, proteins, and lipids, further contributing to genetic instability. UVA rays penetrate deeper into the skin and primarily cause indirect DNA damage through these oxidative processes. Over time, these accumulated mutations can transform normal skin cells into cancerous ones, leading to various forms of skin cancer including basal cell carcinoma, squamous cell carcinoma, and the more dangerous melanoma. Key strategies for prevention include:
- Using broad-spectrum sunscreen with a sun-protection factor of 15 or greater
- Wearing hats or other shade-protective clothing
- Avoiding the outdoors during midday hours (10 a.m. to 3 p.m.)
- Avoiding indoor tanning By prioritizing sun protection and minimizing UV exposure, individuals can significantly reduce their risk of developing skin cancer.
From the Research
Chemical Mechanism of UV-Induced Cancer
The chemical mechanism of UV-induced cancer involves the formation of DNA lesions, which can lead to mutations and the development of skin cancer. The main types of DNA lesions formed by UV radiation are:
- Cyclobutane pyrimidine dimers (CPDs) 2, 3, 4
- Pyrimidine (6-4) pyrimidone photoproducts (64PPs) 3, 4
- 8-oxo-7,8-dihydroguanine (8-oxoGua) 3, 4
Formation of DNA Lesions
The formation of these DNA lesions depends on the wavelength of the incident photons. UVB radiation (280-320 nm) is more effective at forming CPDs and 64PPs, while UVA radiation (320-400 nm) is more effective at forming 8-oxoGua 4. The chemical nature of the DNA lesions also depends on the presence of oxygen and other molecules that can react with the excited states of the DNA bases 3.
Role of DNA Repair Mechanisms
The nucleotide excision repair pathway is the main mechanism for removing UV-induced DNA lesions 2. However, if the DNA lesions are not repaired, they can lead to mutations and the development of skin cancer. The p53 tumor suppressor gene is a common target of UV-induced mutations, and its inactivation can lead to the development of skin cancer 5.
Prevention of UV-Induced Cancer
The use of sunscreens can help prevent UV-induced cancer by reducing the amount of UV radiation that reaches the skin 6. However, not all sunscreens are equally effective, and some may not provide adequate protection against UVA radiation 6. The most effective way to prevent UV-induced cancer is to avoid exposure to UV radiation, especially during peak hours, and to use protective measures such as clothing and sunscreens.
Key Findings
Key findings from the studies include:
- UV radiation can cause DNA damage, including the formation of CPDs, 64PPs, and 8-oxoGua 2, 3, 4
- The formation of these DNA lesions depends on the wavelength of the incident photons 4
- The nucleotide excision repair pathway is the main mechanism for removing UV-induced DNA lesions 2
- The use of sunscreens can help prevent UV-induced cancer, but not all sunscreens are equally effective 6