Differences in Risk Factors for Melanoma in Young and Middle-aged Higher-risk Patients

Discussion

Several findings emerged from this study of 330 young and middle-aged cutaneous melanoma patients. A higher number of patients (41% of middle-aged and 47% of young) were defined as higher risk owing to FH, OM, HNC or DN compared to an earlier study (3), in which 11% of <40 and 33% of 40-59-year-old patients were defined as high-risk patients. This difference may, however, be explained by the different definition of risk factors between studies, as in our study DN was also counted in. The problem in comparing findings from the literature, is that, according to our knowledge, there are only a few studies which compare risk factors for melanoma in young and middle-aged adults.

The ratio of patients with FH is in agreement with other studies, but findings differ with regards to age distribution (8, 13, 14). In our study, young adults were more likely to have FH compared to middle-aged, while in other studies patients older than 40 years were more likely to have FH. Whether this difference can be explained by country-specific variations in the population remains unclear. Different results have also been observed between studies concerning the Breslow thickness of melanomas in patients with FH. Li et al. (8), have found that individuals with FH might be more likely to develop thicker melanomas, while Chiarugi with cowriters (14) did not find differences in thickness between familiar and sporadic melanomas. We found that a majority of patients with FH had thin melanoma, which is in agreement with the study by Aguilera and cowriters (13). This finding suggests that melanoma patients with FH may have an increased risk awareness and could benefit from an early detection of melanoma.

A high number of nevi is the most significant phenotypic risk factor for melanoma and is in part genetically determined (15). Having HNC was the most common host risk factor for melanoma in both young and middle-aged adults. In these patients, melanomas were more likely thin and located in the trunk area, confirming data from previous melanoma studies (4, 15). It has been suggested that individuals with HNC may be more likely to practice skin self-examination, which may lead to an earlier detection of melanoma (4). There is also a possibility that the genetic determinants of nevi number may be associated with biological differences in melanoma tumors (15). Most patients with melanoma, however, did not have HNC. The total nevus count should not be the only reason for performing a skin examination or determining a patient's risk-status.

Melanomas in patients with DN were more likely to be thinner and presented more commonly in middle-aged patients; observations adding support to prior studies (4, 5). The subtype of melanomas, however, differed between studies. In our study, melanomas in patients with DN were less likely to be SSM and more likely NM compared to patients without DN or other host risk factors. In other studies, SSM was a more common subtype and NM less frequent one in patients with DN compared to patients without DN (4, 5). SSM is considered to be less aggressive and is more often detected as a thinner tumor with a slower growth compared to NM (16).

The proportion of patients with biopsy-proven OM was higher here (11%) compared to previous studies with regards to all age groups (1.2-8.2%) (17-19). The reason for this difference between studies is not clear, however, one reason may be the different age groups studied. In our study, only patients 60 years or younger were included. In prior studies, OM were diagnosed in patients with different predominance on gender and age. Observations supporting both males of an older age (17) and females of an early age (19) have been published. In our study, OM were more likely diagnosed in the middle-aged group with female predominance. Even one tenth of ≤60-year-old melanoma patients developed a second primary melanoma. Careful education of melanoma patients could facilitate an earlier diagnosis of a subsequent second primary melanoma.

When comparing behavioral risk factors, we observed that young adults had less excessive sun exposure during adulthood and a history of sunburn during childhood compared to middle-aged patients. It has been suggested in earlier studies that public health campaigns promote awareness of the risk of sun exposure in Australia and Europe and may have contributed to stabilizing or declining the melanoma incidence rates in young adults (1). Whether this is true also in our population remains to be studied. In this study, over one third of the patients with high-risk host characteristics had a history of excessive intermittent sun exposure or a history of sunburns during childhood. Similar results have been previously reported by Chiarugi et al. (14) in patients with FH. This finding suggests that patients with host risk characteristics are not careful enough to prevent melanoma. Continued close monitoring and information about sun protection of high-risk population is necessary.

We acknowledge several limitations in our study. First, certain subgroups are limited by the small numbers of patients. The disproportion between the two age groups of the study, can be explained by the different distribution of melanoma depending on age but can still limit the interpretation of the results. Second, this study is limited to studying patients at an academic center rather than from a cohort of a wider population. Despite this limitation, our patients were referred from surrounding regions as well. Third, the familial status was based on patients' self-reported family history. To minimize the risk of recall we applied the criteria with no more distance than the first-degree relatives. Fourth, skin cancer patients may overreport or underreport their sunburn or sun exposure experience, producing biased estimates of the true association. On the other hand, the majority of studies use verbal reports or self-reports to measure habitual sun exposure. Despite well-known limitations of verbal reports, these measures were suggested to be the most practical for both population surveillance and intervention research (20).

We think that these results lead to some scientific and health educational suggestions. Our findings support prior studies, while also offering distinct new information about melanomas in a different country-specific population. The findings from this study may help identify strategies to further stratify patients for more targeted patient education and potential screening.

In conclusion, young and middle-aged adults have differences in risk factors for melanoma. Our data support more intensive skin cancer screening for patients of 60 years of age or younger with DN. The characteristics of melanomas in higher-risk patients in our study population have some differences compared to the characteristics described in earlier studies, supporting the existence of country-specific variations in melanomas. Characterization of these features may assist in understanding of heterogeneity of melanoma and targeting country-specific cancer treatment and control activities.