Risk calculator for health professionals

Melanoma incidence rates increase with age in both sexes, with a sharper rise in incidence rates observed in males over 60. The overall increase in incidence of melanoma is almost entirely attributable to rising incidence in people over 60 years. Melanoma is rare under 15 years of age.

In Australia, melanoma is the most common cancer among those aged 15-59.

Australia and New Zealand have the highest rates of melanoma in the world. In Australia, 1 in 14 males and 1 in 22 females will develop invasive melanoma in their lifetime (to age 85).

Melanoma is now the third most common malignancy in Australia for both sexes, behind colorectal, breast and prostate cancer. Incidence is rising steadily at 3-4% per year 1. The rise in incidence is much steeper in men than women.

Melanoma is most commonly found on the trunk in males and limbs in females. Prognosis is a little better in women.

Mortality is rising in men over 60 years but stable in women1.

In Australia, incidence of melanoma increases with proximity to the equator.

Latitude of residence correlates well with UV exposure even though it does not account for individual behaviours or migration from areas of different UV indices. The effect of latitude is greatest on skin areas intermittently exposed to the sun.

For the purposes of this risk model, Australia has been divided into 3 zones based on latitudes of the eastern states.

Data taken from Victorian, NSW and Queensland Cancer Registries.

Multiple freckles on the arm and forearm.

Multiple freckles on the back.

Freckles are areas of increased melanin pigmentation. They are more common in children and those with red hair, and fair skin. This model uses freckles in adulthood as a risk factor (RR=2.05) 6. Childhood studies report higher relative risks.

Freckles reflect melanocyte overactivity as a result of UV exposure. They fade in the winter months. They must be distinguished from solar lentigines which persist indefinitely and result from a severe sunburn or chronic solar damage. Freckle density is greater with proximity to the equator, hence there is a correlation with latitude6.

Melanoma risk increases with freckle density, usually assessed on the shoulders and upper back. This risk is independent of the risk associated with naevi, phenotype and phototype.

Hair colour was selected for this risk model as an easily assessed phenotypic characteristic. Red hair has also been shown to be the phenotypic trait best representing the presence of MC1R variants, a known genetic marker of melanoma risk 5.

This is most accurately assessed by considering hair colour at age 20. Redheads are at greatest risk with almost three times the risk of darker haired people. Blond or fair haired people have 1.5 times the risk 6.

The risk of developing a second melanoma is in the order of 0.5% per year (or 4.5% risk over 10 years)12. Risk for a further melanoma increases progressively with increasing numbers of primary melanomas. Following 2 primary melanomas the risk for a third is of the order of 3% per year.

The risk of a second melanoma is higher in males over 70. Incidence of second primaries also peaks around the ages of 25-34, which may reflect the association with cases of familial melanoma. Those diagnosed with their first melanoma before age 45 have about twice the risk of a second primary as the older group. It has been reported that 10.5% people with multiple melanoma have a positive family history.

From the few studies available, it is difficult to assess the extent to which past history acts as an independent risk factor. There is evidence that it is a strong risk factor and we felt it was important to include it in this model. In the context of the other six predictors, however, its effect may be over-stated. While this impacts on absolute risk prediction it has little or no bearing on the model's ability to discriminate between individuals of high and low risk.

A large Basal cell carcinoma (BCC) on the back with a smaller BCC below it

A Squamous cell carcinoma (SCC) on the ear

Basal cell carcinomas are the most common malignancy in white populations. Both basal cell and squamous cell carcinomas are important risk factors for melanoma. They share common risk factors with melanoma, specifically sun exposure and phenotype. A shared pathway of induction is likely. UV radiation causes DNA damage and mutations in tumour suppressor and proto-oncogenes responsible for unrestricted cell turnover.

Family history is a complex risk factor for melanoma. It is difficult to tease out the proportion of risk that can be attributed to susceptibility genes versus pigmentary characteristics (also genetically determined) and environmental factors. Despite this, studies consistently show that melanoma in a first degree relative (parent, sibling, child) increases risk of melanoma approximately 2 fold 6.

Melanoma risk increases with increasing numbers of affected family members. Individuals with known mutations that predispose to melanoma make up a small proportion (around 2%) of individuals with a positive family history.

There are two main tumour suppressor genes linked with susceptibility to melanoma. Mutations in CDKN2A may be found in 25 to 40% of members of melanoma-prone families, with CDK4 mutations much less common. An Australian study found mutations in CDKN2A in 10.3% of a high risk population, and estimated that only 0.2% of melanomas in Australia were due to CDKN2A mutations8. The likelihood of finding a mutation in CDKN2A rises from about 5% in families with 2 affected members, to 20-40% if 3 or more family members are affected 9. Furthermore, residence in areas with high rates of melanoma significantly increases the penetrance (ie. probability of developing melanoma amongst mutation carriers).