51
this kind of analysis may be useful in discerning the stages of tumor progression
based on H2AX activation levels.
Another key component of the DDR that has been evaluated in the context of skin
cancer is the protein ATM, which becomes activated (pATM) upon contact with UV
radiation. The pATM expression patterns were evaluated in cultured keratinocytes,
skin explants, and a spectrum of premalignant to malignant keratinocyte skin lesions.
pATM was observed in the nucleus of a normal skin cell, 30 min after UV radiation,
and it returned to its basal localization after 2 h. On the other hand, pATM expression in precancerous keratinocyte lesions was greater when compared to the invasive
lesions where pATM was weaker (Ismail et al. 2011). These results showed a more
active DDR in the first stages of this type of cancer, which are consistent with the
hypothesis that the DDR acts as a barrier to cutaneous tumor formation. In fact, early
precursor lesions expressed markers of an activated DDR in several types of tumor,
with a diminishing response in more advanced cancers. This highlights the importance of detecting and quantifying DNA damage (Figueroa-González and PérezPlasencia 2017). Although these experiments are very promising, there remain many
unanswered questions to be addressed in future studies. Beyond the DDR proteins
mentioned above, other markers involved in several cell metabolic pathways have
been characterized as biomarkers for skin cancer. The utility of all these proteins as
biomarkers needs to be validated in future clinical trials, and more research is needed
in order to introduce them in intervention programs of secondary prevention.
4.3 Impact Sustainability: Final Remarks
Skin cancer incidence is increasing. The WHO reports between 2 and 3 million nonmelanoma skin cancers and 132,000 melanoma skin cancers globally each year;
1 in every 3 cancers diagnosed is a skin cancer. According to Skin Cancer Foundation
Statistics, one in every five US citizens will develop skin cancer in their lifetime,
and more people are diagnosed with skin cancer each year in the United States than
all other cancers combined.
Several factors are responsible for skin cancer incidence, and some of them are
more easily treated than others. Primary prevention is not always sufficiently effective. Without adequate widespread, comprehensive implementation and primary
prevention strategies may have little effect on attitudes toward sun protection and
sunburn prevention at the community level. Social and contextual factors within
communities can also create barriers to reducing UV exposure. Moreover, better
politics to reduce the risk of skin cancer among outdoor workers is needed.
Fortunately, after WHO’s designation of indoor tanning devices as Class 1 human
carcinogens (the highest-risk level), several countries have banned indoor tanning,
specifically, Brazil and Australia. In addition, France, Spain, Portugal, Germany,
Austria, Belgium, the United Kingdom, Australia, Iceland, Italy, Finland, and
Norway prohibit indoor tanning for youth younger than 18 years old (Mitchell 2018;
“From Australia to Brazil: sun worshippers beware” 2009; Stark 2009). Although
4 SDG 3 Good Health and Well-Being
this kind of analysis may be useful in discerning the stages of tumor progression
based on H2AX activation levels.
Another key component of the DDR that has been evaluated in the context of skin
cancer is the protein ATM, which becomes activated (pATM) upon contact with UV
radiation. The pATM expression patterns were evaluated in cultured keratinocytes,
skin explants, and a spectrum of premalignant to malignant keratinocyte skin lesions.
pATM was observed in the nucleus of a normal skin cell, 30 min after UV radiation,
and it returned to its basal localization after 2 h. On the other hand, pATM expression in precancerous keratinocyte lesions was greater when compared to the invasive
lesions where pATM was weaker (Ismail et al. 2011). These results showed a more
active DDR in the first stages of this type of cancer, which are consistent with the
hypothesis that the DDR acts as a barrier to cutaneous tumor formation. In fact, early
precursor lesions expressed markers of an activated DDR in several types of tumor,
with a diminishing response in more advanced cancers. This highlights the importance of detecting and quantifying DNA damage (Figueroa-González and PérezPlasencia 2017). Although these experiments are very promising, there remain many
unanswered questions to be addressed in future studies. Beyond the DDR proteins
mentioned above, other markers involved in several cell metabolic pathways have
been characterized as biomarkers for skin cancer. The utility of all these proteins as
biomarkers needs to be validated in future clinical trials, and more research is needed
in order to introduce them in intervention programs of secondary prevention.
4.3 Impact Sustainability: Final Remarks
Skin cancer incidence is increasing. The WHO reports between 2 and 3 million nonmelanoma skin cancers and 132,000 melanoma skin cancers globally each year;
1 in every 3 cancers diagnosed is a skin cancer. According to Skin Cancer Foundation
Statistics, one in every five US citizens will develop skin cancer in their lifetime,
and more people are diagnosed with skin cancer each year in the United States than
all other cancers combined.
Several factors are responsible for skin cancer incidence, and some of them are
more easily treated than others. Primary prevention is not always sufficiently effective. Without adequate widespread, comprehensive implementation and primary
prevention strategies may have little effect on attitudes toward sun protection and
sunburn prevention at the community level. Social and contextual factors within
communities can also create barriers to reducing UV exposure. Moreover, better
politics to reduce the risk of skin cancer among outdoor workers is needed.
Fortunately, after WHO’s designation of indoor tanning devices as Class 1 human
carcinogens (the highest-risk level), several countries have banned indoor tanning,
specifically, Brazil and Australia. In addition, France, Spain, Portugal, Germany,
Austria, Belgium, the United Kingdom, Australia, Iceland, Italy, Finland, and
Norway prohibit indoor tanning for youth younger than 18 years old (Mitchell 2018;
“From Australia to Brazil: sun worshippers beware” 2009; Stark 2009). Although
4 SDG 3 Good Health and Well-Being