The main risk for both Malignant Melanoma and Non-Melanoma Skin Cancers is exposure to UV light, whether direct from the sun or from artificial sources such as sun-beds. However there may be other unexplored risk factors which may add to our better understanding of how skin cancer develops. The Metabolic Syndrome and Cancer Project (Me-Can) (a research group looking at how metabolic factors affect a range of cancers) has looked at the associations of metabolic aberrations with Malignant Melanoma and Non-Melanoma Skin Cancers and concluded that mechanisms linked to blood pressure may be involved in causing Malignant Melanoma and that Squamous Cell Carcinoma in women could be related to glucose and lipid metabolism. Their research is due to be published in the British Journal of Dermatology on 25th April 2012
Gabriele Nagel (University of Ulm, Germany and the Agency of Preventive Medicine, Bregenz, Austria) said:
“This data supports the notion that a healthy life-style avoiding high blood pressure and being overweight (which has already been shown to decrease risk of cardiovascular disease and diabetes) may also be associated with a decreased risk of other diseases such as skin cancer. We believe that looking at risk factors other than sunlight exposure for both Malignant Melanoma and Non-Melanoma Skin Cancers will increase our understanding of the pathogenesis of these diseases and may open novel lines of research that could contribute to better treatment, screening and prevention of skin cancers.”
The researchers, based in Sweden, Norway, Germany and Austria had access to a large cohort of men and women through the Me-Can project. This project was set up in 2006 in order to create a large pooled cohort to investigate factors of the metabolic syndrome associated with cancer risk.
The Me-Can cohort of 541,254 subjects had a mean follow up of 12 years and an incidence of 1728 Malignant Melanomas, 230 of which were fatal, and 1145 Non-Melanoma Skin Cancers – most of which (873) were Squamous Cell Carcinoma. The researchers looked at body mass index (BMI), blood pressure, glucose, cholesterol, triglycerides and combined metabolic syndrome (MetS) score4.
The results suggested that:
- Increased blood pressure was associated with increased risk of malignant melanoma in men and women
- Increased blood pressure in women was also associated with fatal malignant melanoma
The researchers hypothesise that the link between blood pressure and malignant melanoma may be shared biological mechanisms: prevention of cell death (anti-apoptotic effects), increased cell division (mitogenic effects) as well as decrease in oxygen supply and an increase in vascular endothelial growth factor receptors production. VGEF is a protein that is secreted by oxygen-deprived cells, such as cancerous cells and which stimulates new blood vessel formation, or angiogenesis, by binding to specific receptors on nearby blood vessels. The lack of oxygen supply has been shown (in other experimental research) to affect cancerous changes in and around melanocytes. Experimental studies have indicated that VEGF may be involved in the initiation of skin cancersiii and hypertension (high blood pressure). Since hypertension is highly prevalent in many western countries, the association between blood pressure and Malignant Melanoma deserves further research.
The strength of this study lies in the design, large size and standardized information of measured exposure factors – this helps to minimize bias due to selection, recall or reverse causation. The limitations of the study are around lack of data on sun exposure, which remains the major risk for skin cancer.
The study also found that in women Squamous Cell Carcinoma (SCC) might be linked to glucose and lipid metabolism. Other studies had already shown that both men and women with Type 1 Diabetes had an increased risk of Non-Melanoma Skin cancer, but those with Type 2 Diabetes did not show the same risk. In the study carried out by Me-Can an increase in triglycerides increased risk of SCC and increased risk was also found for other cancer sites (e.g. cervical). The researchers speculate that the altered lipid (fat) metabolism could be related to infectious components in the development of cancers – such as the association of Human Papilloma Virus (HPV) with Non-Melanoma Skin Cancer. The researchers felt that further work needed to be done to establish more clearly these metabolic risk factors in Non-Melanoma Skin Cancer.
The work was supported by a grant from the World Cancer Research Fund (Grant 2007/09 and 2010/247).
The Metabolic syndrome and Cancer Project (Me-Can)
The Metabolic syndrome is a term used to refer to a cluster of metabolic risk factors which often occur in combination but may also occur individually, they include: obesity, hypertension, insulin resistance/hyperglycaemia and dyslipidaemia. These factors have both separately and jointly been linked to an increased risk for cardio-vascular diseases. The Me-Can project seeks to find out about the risks in relation to cancer. Recent studies by the project have focused on an association between the metabolic syndrome and risk of specific cancers (mainly gynaecological, colorectal and prostate) or between a single factor in the syndrome and cancer risk.
The Me-Can project was set up in 2006 in order to create a large pooled cohort to investigate factors of the metabolic syndrome and cancer risk. Principal Investigator on the project is Par Stattin. Using existing cohorts in Norway, Austria and Sweden, the project was able to call on a large number of subjects. In all the cohorts subjects were measured for height, weight, systolic and diastolic blood pressure, blood/plasma/serum levels of glucose, total cholesterol and triglycerides.
Altogether the cohorts represented just under one million subjects. Following data cleaning and selection of subjects and observations a total of 578,700 subjects were available to be used in Me-Can studies on metabolic syndrome and cancer risk.
The strengths of the Me-Can project are the large data-set from a number of population-based surveys, with almost complete coverage of data for exposure factors in all cohorts, and the access of data on repeated health examinations for a substantial number of subjects. The project also uses hiqh-quality national registers to follow up subjects. The two main limitations on the project are the lack of detailed data on possible confounders and on tumour characteristics and cancer treatment and the different methods of measuring exposure factors in different cohorts.
Skin cancer includes Malignant Melanoma and Non-Melanoma Skin Cancer – the main subtypes of which are Squamous Cell Carcinoma (SCC) and Basal Cell Carcinoma (BCC).
Scandinavian countries have the highest Malignant Melanoma rates in Europe. Exposure to UV-radiation, particularly during childhood, is the major risk factor for skin cancer. However, gender and age related differences in the localization of Malignant Melanoma suggest that hormonal and lifestyle factors could also be involved in the disease pathogenesis.
In the UK Skin cancer incidence continues to rise and over 100,000 people are newly diagnosed with the disease every year. Malignant Melanoma, the most deadly form of the disease, is the fastest rising common cancer and causes over 2,000 deaths in the UK each year. Most cases are curable if detected early, but if diagnosis is delayed and the cancer spreads then chances of surviving are greatly reduced.
Written and supplied by British Association of Dermatologists