Monday, 16 June 2008

Briffa on skin cancer

John Briffa's latest post attempts to cast doubt on the association between skin cancer and sun exposure:

"I was therefore interested to read over the weekend an editorial in the British Medical Journal which highlights the importance of sunlight and vitamin D in health...

There are three main forms of skin cancer: what are known as ’squamus cell carcinoma’ and ‘basal cell carcinoma’, and ‘malignant melanoma’. The first two tend to develop on the most sun-exposed parts of the body (e.g. the top of the ear) and are generally very treatable. Malignant melanoma, on the other hand, is generally much less treatable, is quite often deadly, and is usually the major reason cited regarding why we should protect ourselves from the sun...

However, is the relationship between sunlight exposure and risk of malignant melanoma as clear-cut as we are generally led to believe it to be? Michael Holick’s editorial contains information that might cause us to question traditional wisdom on this. He writes: “Notably, non-melanoma skin cancers occur on the most sun exposed areas, such as the face and hands, whereas most melanomas occur on the areas least exposed to the sun [2]. Intermittent and occupational sun exposure has been found to reduce the risk of malignant melanoma [2–5].”

In short, Professor Holick appears to be asking: “If sunlight exposure causes malignant melanoma, how come it tends to develop on parts of the body that are not typically very sun-exposed, and how come there is evidence linking sun-exposure with reduced risk of this condition?” Professor Holick appears to cast considerable doubt on the notion that excessive exposure to sunlight is a major risk factor for malignant melanoma."

Apart from being a little concerned about his attitude to skin cancer (basal cell carcinoma is fairly benign but squamous cell carcinoma has a risk of around 4% of spreading, both need surgical excision, and this isn't always easy or complete) I wondered where he got this view from. The medical consensus is that sun burn (especially in early life) is associated with malignant melanoma (with chronic sun exposure, such as from outdoor jobs, associated with basal cell and squamous carcinoma). Here's what the NHS says:

"There is a definite link between sunbathing (including using a sunbed) and malignant melanoma. Probably the most dangerous type of sunbathing is a short, sharp period of intense exposure, either in a single day or over a short period such as a holiday. The larger the area of skin exposed, the greater the risk. Getting sunburnt increases the risk further. It is the ultraviolet (UV) part of sunlight that does the most damage.
Severe sunburn in childhood can significantly increase your chances of developing malignant melanoma in later life.
It is also possible that you have more chance of developing malignant melanoma if someone in your family has also had one. Family history is most likely to be the cause if you haven't had excessive exposure to the sun. About one in 10 people with a melanoma have family members who have also had at least one.
You may also be at a greater risk if you have a large number of non-cancerous(benign) birthmarks."

The BMJ does indeed contain an editorial by Michael Holick, which mentions in passing that melanomas occur on areas least exposed to the sun:

"Excessive exposure to sunlight causes an estimated annual loss of 1.6 million disability adjusted life years (DALYs)—0.1% of the total global disease burden in the year 2000. This compares with the loss of about 3.3 billion DALYs from bone disease caused by vitamin D deficiency as a result of too little exposure to sunlight.11 These figures do not take into account the other potential health benefits of sun exposure and vitamin D sufficiency in reducing other chronic diseases, which account for 9.4% of total global disease burden. Notably, non-melanoma skin cancers occur on the most sun exposed areas, such as the face and hands, whereas most melanomas occur on the areas least exposed to the sun.12 Intermittent and occupational sun exposure has been found to reduce the risk of malignant melanoma.1 4 5 12"
So does this observation support Briffa's rejection of the melanoma-sun exposure link? Well let's look at the papers Holick links to in his editorial.

Number 1:
"Children and young adults who are exposed to the most sunlight have a 40% reduced risk of non-Hodgkin's lymphoma65 and a reduced risk of death from malignant melanoma once it develops, as compared with those who have the least exposure to sunlight.66"
So, this tells us that once you have developed melanoma sunlight exposure improves prognosis, but has nothing to say on the question of sunlight and malignant melanoma incidence.

Number 4:
"An ecologic study was performed using age-adjusted annual mortality rates for Caucasian Americans for 1950-69 and 1970-94, along with state-averaged values for selected years for alcohol consumption, Hispanic heritage, lung cancer (as a proxy for smoking), poverty, degree of urbanization and UVB in multiple regression analyses. Results: Models were developed that explained much of the variance in cancer mortality rates, with stronger correlations for the earlier period. Fifteen types of cancer were inversely-associated with UVB. In the earlier period, most of the associations of cancer death rates with alcohol consumption (nine), Hispanic heritage (six), the proxy for smoking (ten), urban residence (seven) and poverty (inverse for eight) agreed well with the literature. Conclusion: These results provide additional support for the hypothesis that solar UVB, through photosynthesis of vitamin D, is inversely-associated with cancer mortality rates, and that various other cancer risk-modifying factors do not detract from this link. It is thought that sun avoidance practices after 1980, along with improved cancer treatment, led to reduced associations in the latter period."

Can't get the full text of this - I note it is evil epidemiology, Briffa's not keen on that as we have learned from his views on MMR - there are multiple potential confounds, but assuming that it found a robust correlation between sun exposure and reduced melanoma (can't tell from the abstract), this doesn't really add anything to what we already know, it doesn't separate chronic sun exposure and acute sun burn, and there have been more detailed studies going beyond epidemiology looking at this (see below).

Number 5:

"Because the mortality rates of CMM [cutaneous melanocytic melanoma] are much higher than those of nonmelanoma skin cancer (in some populations, more than a factor of 10 higher), this problem is the most important one to solve regarding the negative consequences of sun exposure. The solution is by no means certain yet. A number of investigators disagree, as we reviewed earlier (12, 13).
The main arguments against the concept that sun exposure causes CMM are that: (i) CMM is more common among persons with indoor work than among those people with outdoor work (14, 15); (ii) in younger generations, more CMMs arise per unit skin area on partly shielded areas (trunk and legs) than on face and neck (16); and(iii) CMMs sometimes arise on totally shielded areas (acral CMM and uveal melanomas). Although the connection between these melanoma types and sun exposure is controversial (1719), their inclusion in the present discussion is justified because of the possible involvement of vitamin D.
However, in our opinion, a significant fraction of CMMs is related to sun exposure (16, 20). The main arguments for this relationship are: (i) the north–south gradients in CMM incidence between Scandinavia and Australia (16), (ii) before the advent of the "top-less" fashion, few women developed CMM on the breast area (13, 16), and (iii) in some animals (Sinclair swine, Monodelphis domestica, the fish Xiphophorus, white horses, angora goats, transgenic mice, etc.) UV exposure leads to CMM (16). The reason that CMM incidence rates decrease with decreasing latitude in Europe is likely because of differences in skin color from region to region."
So we have competing epidemiological observations, none of which is definitive (and I'd argue that their points ii and iii are irrelevant, including the idea that because melanoma more commonly arises on trunk or leg it can't be associated with sun exposure - since these are areas where acute sun burn is common - which could explain the male preponderance for melanoma on the back, and females on the legs).

Number 12:
"Acute and chronic sun exposure may exert different effects in the sequel from common melanocytic nevi, clinically atypical nevi to malignant melanoma (Elwood and Jopson, 1997;Gilchrest et al, 1999). Acute painful sunburns may promote the development of common melanocytic nevi, clinically atypical nevi, and thus, or possibly independently, the development of malignant melanoma. Although there are some contradictory findings regarding the association between chronic lifetime sun exposure and malignant melanoma, most studies found that chronic lifetime sun exposure was associated with a protective effect on the development of malignant melanoma.
This could be explained by the protective mechanisms, which are associated with heavy chronic sun exposure, such as tanning and skin thickening, but this may not be the total explanation (Elwood and Jopson, 1997;Gilchrest et al, 1999). Although it cannot be excluded that sun exposure during adult life promotes the disappearance of nevi, which could be an additional explanation of a decreased risk of malignant melanoma, in our study the disappearance of nevi was completely explained by increasing age of the individuals, and chronic sun exposure had no additional effect."
This case-control study confirmed the consensus that acute sun burn can increase the risk of malignant melanoma. It also supported the view that chronic sun exposure reduces the incidence.

So overall I'd say that this editorial in the BMJ, which really only tangentially mentions a couple of observations about melanoma incidence, far from "[casting] considerable doubt on the notion that excessive exposure to sunlight is a major risk factor for malignant melanoma" adds precisely nothing to what we already know about malignant melanoma and sun exposure, or at least, adds nothing to what well informed clinicians know about the link between malignant melanoma and sun exposure.


Jon said...

Briffa's lack of useful contribution to people's knowledge on this topic is troubling when it is presented as an item that should be meaningful for the intended audience of his readers.

Thanks for this detailed assessment of the issue and highlighting that there isn't a major shift in thinking.

Robert said...

I didn't know that anyone thought that the North South gradient of melanoma in europe is evidence against the hypothesis that sun burn causes melanoma. Now I think such people are silly. Vulnerability to UV varies by latitude of where your ancestors survived. If you never tan, burn easily and have many irregular freckles, you must be very careful about UV. I once knew a graduate student with those features. She died of a melanoma in her early thirties.

If people from the extreme North or the always cloudy parts of Europe go on vacation to the Mediterranean and roast themselves in the Sun for a few weeks, they are playing with Melanoma.

Besides if you want more vitamin D you can just take vitamin pills (watch out too much is toxic)