More cancer after melanoma

“Having skin cancer doubles the risk of being diagnosed with some other forms of cancer” reports The Daily Telegraph. The newspaper says a study has found that people diagnosed with non-melanoma skin cancer were almost twice as likely to later develop the rarer, more dangerous melanoma form.

In this study, researchers examined the records of over 20,000 skin cancer patients to calculate the risk of developing a second case of cancer. The researchers did find that overall risk of a second cancer more than doubled following melanoma. However, as this study did not collect data on lifestyle factors such as sun exposure or smoking, it is unable to discount these as contributing factors to the incidence of cancer.

It does seem sensible, as Cancer Research UK says, to provide information on the increased risks to survivors of a first cancer in an attempt to reduce their risk of developing a second cancer. Good information on skin cancer, and cancer risks in general, is invaluable whatever the cause.

Where did the story come from?

This research was conducted by Dr Marie Cantwell and Professor Liam Murray, along with colleagues from Queen’s University Belfast and the International Agency for Research on Cancer. Sources of funding are not reported. The study was published in the peer-reviewed, British Journal of Cancer .

What kind of scientific study was this?

This is a cross-sectional study using registry data on patients with new cases of skin cancers recorded between 1993 and 2002 in Northern Ireland.

The researchers were aware of increasing rates of these types of cancers worldwide, including Northern Ireland. But prior to this study there was no convincing data looking at whether individuals with skin cancer are at risk of developing other malignant cancers. Some studies have shown a reduced risk of prostate and bowel (colorectal) cancer for those who previously developed skin cancer.

The data used was from the Northern Ireland Cancer Registry, a population-based registry that routinely receives data on all cancers diagnosed by hospitals, pathology laboratories and X-ray facilities.

The data included both melanoma skin cancers and the more common non-melanoma skin cancers (basal cell cancers or squamous cell cancers). Melanoma skin cancers are rarer and more dangerous, and can occur on any part of the body. Non-melanoma skin cancers usually occur on areas of skin that are exposed to the sun. 

The researchers excluded data on some patients who were diagnosed before 1992. They also excluded data on anyone who was diagnosed outside Northern Ireland (and therefore could not be followed for subsequent cancer risk), and anyone over 100 years old when diagnosed.

The authors of the study used standard statistical methods of analysis, and adjusted their results for the sex of the patients.

What were the results of the study?

Over nine years, the registry saw 14,500 new cases of basal cell skin cancer, 6405 of squamous cell skin cancer and 1839 of melanoma. Overall, the subsequent risk of a second cancer was more than double after melanoma. The risk of a second cancer, compared with the general population, increased 9% after basal cell cancer, and 57% after squamous cell cancer.

The absolute rates were calculated, giving an indication of how commonly these cancers develop for the first time within the community. Each year, new basal cell cancers occurred in 86.6 out of 100,000 people; new squamous cell cancers in 38.4 people out of 100,000 people; and melanoma in 11 people out of 100,000 each year.

Developing a subsequent melanoma was also three times more likely in men, but no more likely in women who had previously had a squamous cell cancer. Subsequent tobacco-related cancers were more likely in both sexes. Women with a squamous cell cancer were less likely to have subsequent breast cancer.

Melanoma was followed by an increased risk of any subsequent cancer, but the results are not given for specific non-skin cancer sites individually. Those who registered with bowel cancer showed an increased risk of basal cell cancer.

What interpretations did the researchers draw from these results?

The researchers say their results show that patients with a basal cell cancer, squamous cell cancer or melanoma have an increased risk of developing a new primary cancer. This is especially true for melanoma in men when compared with the general population. The researchers suggest that this may partly reflect the fact that these tumours share risk factors, such as UV exposure or smoking.

The authors highlight the fact that their results contradict earlier reports of a decreased risk of prostate cancer after skin cancer. This link was previously thought to be caused by an increased production of vitamin D in people exposed to UV light.

What does the NHS Knowledge Service make of this study?

There are strengths to this study, which has carefully collected a large amount of data from an existing population-based registry.

The advantage of a population-based registry (particularly one that includes cancer notifications from community labs and X-ray departments) is that loss of individuals during follow-up may be low. Also, the prognosis for these patients is more likely to represent the overall picture for all patients rather than just the most severe ones, as seen by hospitals.

The researchers also acknowledge there were some limitations to the study:

• The mean period of follow-up was only four years in this 10-year study. This was because the patients at diagnosis were generally older, particularly those with squamous cell cancer. This meant that many of them died of other causes before the end of the study. The authors did not adjust for this competing risk in their analysis.
• Most patients in the study identified themselves as white, therefore the results may not be relevant to other racial groups, which are known to have different risk levels for these types of cancer.
• The authors did not have information about underlying factors that may explain some of the increased risk, meaning that the factors could not be adjusted for in the analysis. These factors include the known risk factor of individual UV exposure, and other potential risk factors such as vitamin D levels, socioeconomic status or smoking.

Though this was a large study, the actual number of second cancers found, particularly melanomas, was quite small. Only 12 cases of melanoma were found among the 549 men who had been registered with a squamous cell cancer. This means that any bias that caused an increase or decrease of just a single person in this group may have had a large effect on the analysis.

Even if some of these associations are significant, the study will need to be replicated. It would also need to take into account other factors such as smoking and socioeconomic status, so that the reasons for this link can be further evaluated.

Sir Muir Gray adds...

I think there will be more to come on this issue...