A nevus-prone phenotype and higher genetic predisposition for melanoma are more important risk factors for the development of a second primary melanoma than higher levels of sun exposure in Queenslanders, research shows.

Data from almost 40,000 adults 40-69 years from the general population enrolled into the QSkin Sun and Health Study in 2010 and 2011 showed 3.1% had a single primary melanoma during the 7.4 years follow-up and 0.6% had two or more primary melanomas.

The study, published in JAMA Dermatology [link here], found the median time to first melanoma was 48.0 months and the median time between first and second melanoma was 18.4 months.

People who developed second primaries were slightly older at baseline than those who only ever developed a single primary (59.3 v 58.2 years; P < .001), and were more likely to have a sun-sensitive phenotype, a self-reported history of excisions for non-melanoma skin cancer, and have a high polygenic risk score (PRS) for melanoma.

Age at diagnosis of first melanoma were similar in those who developed a single melanoma and those who developed two or more primary melanomas (62.3 v 62.7 years). The mean age at second melanoma diagnosis was 64.6 years.

“We found no statistically significant differences between the median thickness of invasive melanomas for those with single primaries, vs first or second melanomas for patients with multiple melanomas,” the study said.

“However, on categorical analysis, we found that a greater proportion of second melanomas were thin (≤1.0 mm) (46 of 49 [93.9%]) compared with first melanomas in both single primary melanoma (335 of 403 [83.1%]) and multiple primary melanoma (52 of 74 [70.3%]) groups.”

The investigators, including Associate Professor Catherine Olsen and Professor David Whitman from QIMR Berghofer, found second melanomas were more likely to be lentigo maligna sub-type and less likely to be superficial spreading subtype compared with first melanomas.

The study found nevus phenotype (nevus density at age 21 years) was more strongly associated with second primary melanomas (HR 6.36; 95% CI, 3.77-10.75) than first primary melanoma (HR 3.46; 95% CI, 2.72-4.40) (P = .01).

“We also found that second primary melanomas had significantly stronger associations with high melanoma PRS than first primary melanoma (HR, 3.28; 95% CI, 2.06-5.23; vs HR, 2.06; 95% CI, 1.71-2.49; P = .03); the estimates were unchanged when the nevus variable was included in the model in an exploratory post hoc analysis.”

The study found similarly elevated HRs for first and second primary melanoma associated with baseline measures of personal sun exposure (sunburns, cumulative sun exposure) and with 1 proxy measure of high cumulative sun exposure (actinic skin lesions treated destructively)

“However, number of past skin cancer excisions (another proxy measure of high cumulative sun exposure) was more strongly associated with second than first melanoma (P = .05).”

“In this large, prospective cohort analysis, findings showed that many of the classic phenotypic risk factors for melanoma were similarly associated with risk of first and second melanomas; however, high numbers of nevi and high genetic predisposition were more strongly associated with second than first primary melanomas,” the investigators concluded.

“The role of diagnostic scrutiny in detecting second and subsequent melanomas has not been investigated fully here and should be the focus of future analyses.”