Does genetic risk modify the effect of skin screening on melanoma detection rates?

Background: Skin screening is associated with higher melanoma detection rates, a potential indicator of overdiagnosis, but it remains possible that this effect is due to confounding by genetic risk.
Objectives: To compare melanoma incidence among screened vs. unscreened participants within tertiles of genetic risk.
Methods: We investigated melanoma incidence in the QSkin Study, a prospective cohort study which for this analysis comprised 15,283 participants aged 40-69 years with genotype data and no prior history of melanoma. We calculated a polygenic score (PGS) for melanoma. We first calculated age-standardised rate (ASR) of melanoma within PGS tertiles, and then measured the association between skin examination and melanoma detection by calculating the hazard ratio (HR) and 95% confidence interval (95% CI), overall and within PGS tertiles.
Results: Melanoma incidence increased with PGS (ASR/100000/yr) tertile 1: 442; tertile 2: 519; tertile 3: 871). We found that the hazard ratios for all melanomas (i.e. in situ and invasive) associated with skin examination differed slightly across PGS tertiles (age- and sex-adjusted tertile 1 HR 1.88, 95% CI 1.26-2.81; tertile 2 HR 1.70, 95% CI 1.20-2.41; tertile 3 HR 1.96, 95% CI 1.43-2.70; fully adjusted tertile 1 HR 1.14, 95% CI 0.74-1.75; tertile 2 HR 1.21, 95% CI 0.82-1.78; tertile 3 HR 1.41, 95% CI 1.00-1.98) but these differences were not statistically significant. Hazard ratios for in situ melanoma associated with skin examination were similar across PGS tertiles. For invasive melanomas, the point estimates appeared highest in PGS tertile 3 in both minimally adjusted (age, sex) and fully adjusted models, however these apparent differences were also not statistically significant.
Conclusions: Genetic risk predicts subsequent melanoma incidence, and is weakly associated with screening behaviour, but does not explain the higher rate of melanoma detection between screened and unscreened people.
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