How to research the effects of the sun (UVR) and cancer

[progressiveman1]

Since skin cancer generally develops much later on in life, it is tough to run any studies on this other than questionnaires. The questions of course are asking the person to recall things that happened several years prior, which concerns me about its validity. One study asked the people to recall how many sunburns they have had in their life (including childhood): they grouped the answers into 0, 1-2, 3-4, 5+. It did show that the higher groups had more than the lower, but each category differs by only a couple and I can't see how the people would be able to be very accurate with the numbers. I'm young and I don't even know my number; it would just be a guess.

Anyways, the point of the thread is to gather up some ideas on how to go about researching the effects of the sun (UV radiation) and skin cancer. What type of studies would be the most valid? Are there any indications that may suggest skin cancer is developing, or does skin cancer just form suddenly? At least when I was studying the effects of fat on atheroscelorsis I could look at body cholesterol, which gave validity to short-term studies.

[Capitalism Forever]

Anyways, the point of the thread is to gather up some ideas on how to go about researching the effects of the sun (UV radiation) and skin cancer. What type of studies would be the most valid?

Certainly not statistical ones like the one you mentioned. Statistics cannot be used to establish causation; all it can do is draw your attention to an area where you might want to investigate if there is perhaps a causal connection.

Apparently, all that the statistics can purportedly show is a correlation between UV exposure at one point in time and cancer several decades later--so it is clear that there is no direct causal link between sunlight and skin cancer. A researcher seeking to prove a connection would have to find an alteration in your body that is caused by the UV rays, i.e. happens right when you are in the sun, and then establish a chain of events leading from this alteration to the development of cancer decades later. Since your skin will consist of a completely different set of cells 30 years from now that it does now, he would have to show how the condition propagates over time--and answer questions like why there is such a long latency, and so on.

But I don't think such research would find anything, and frankly, I'd consider it a complete waste of money. There are much more important and less far-fetched things for biologists to investigate. The rational thing to do based on the evidence we have at the moment is to conclude that there is presumably NO connection between the sun's UV radiation and skin cancer.

[DavidOdden]

A starting point would be a controlled experiment where subjects were exposed to UV on one arm but not the other, and determine whether the exposed arm developed cancers at a higher rate. It would be very expensive to conduct the study though, having subjects come in for weekly treatments over the course of years (it would be especially challenging to get long-term compliance with unpaid volunteers). It would be possible to accelerate the process by using high-energy short-wavelength UV, but then the conclusions would not carry over to exposure to sunlight. There is a review article here with a number of citations, which you could follow up on.

[progressiveman1]

I'm looking through the abstract of this study that I got from DO's provided review, but I can't figure out how the researchers can conclude that "these findings provide the first objective evidence for the central role of UV radiation in the development of AFX(atypical fibroxanthoma)." Granted, I only have the abstract to work with. However, the only thing I can see them prove is that there were certain types of mutations in certain genes in atypical fibroxanthoma victims. Do you guys see them prove anything otherwise?

[~Sophia~]

but I can't figure out how the researchers can conclude that "these findings provide the first objective evidence for the central role of UV radiation in the development of AFX(atypical fibroxanthoma)."

UV induced DNA damage has a distinctive characteristic of being typically at dipyrimidine sites, with a prevalence of single, and in particular double, CC to TT transitions. These guys observed that same type of mutations.

[progressiveman1]

UV induced DNA damage has a distinctive characteristic of being typically at dipyrimidine sites, with a prevalence of single, and in particular double, CC to TT transitions. These guys observed that same type of mutations.

Thanks for pointing that out. I guess I can trust your judgment since you're a molecular biologist. And that is an influential stat considering they observed that "all but one mutation took place at dipyrimidine sites", and "four cases showed C to T transitions (including two CC-TT double base substitutions)." That's out of a total of 10 cases.

Does a C to G transversion have anything to do with UV induced DNA damage?

[progressiveman1]

There is a belief that UV induced DNA damage can cause types of cancer because some of the DNA isn't successfully repaired after the stressor. I found an interesting study that shows "no statistically significant association between melanoma risk and DRC by itself was found." However, "DRC strongly influenced CMM risk in individuals with a low tanning ability or dysplastic nevi."

[progressiveman1]

I have been very suspicious of the validity of questionnaire-type studies, and they are actually the norm for studies on UV radiation. But I realized that I could still get some value out of those studies if I narrow my criteria, and only take into account questions that are most likely to be answered accurately. With the latest study I posted involving DNA repair capacity (DRC), I focused my efforts on people's sun-sensitivity (how easily you tan or burn), which will usually be accurately reported by the person since it is a variable that is constant and easily noticeable.

Studies 1, 2, 3, and 4, show an increased risk of melanoma-type cancers in sun-sensitive people compared to non-sun-sensitive people.

[~Sophia~]

The most important defense mechanisms that protect human skin against UV radiation (or its effects) are 1) melanin synthesis and then 2) repair mechanisms. Low pigmentation capacity and rare defects in DNA repair are mainly responsible for protection failures.

Several key genes are responsible for skin cancer development: ras oncogenes (when activated (gain of function mutations) - contribute to the malignant phenotype), and p53 and PTCH tumour suppressor genes (loss of function).

Approximately 50% of BCCs show a p53 mutations (with characteristic UV signature) which results in loss of tumor suppres

sor function. Approximately 50% of all tumors have a mutated PTCH gene and 70% display loss of heterozygosity in the PTCH locus. Loss of normal PTCH function due to mutations results in promoting proliferation rather than differentiation.

read: This and This (fig 1 is good cartoon explaining molecular events).

Edited May 23, 2008 by ~Sophia~