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At present, the role of germline genetic factors in determining cutaneous melanoma (CM) survival is not well understood
.
A study published in J Transl Med conducted a meta-analysis of melanoma-specific survival (MSS) from a genome-wide association study (GWAS) and examined whether CM susceptibility polygenic risk scores (PRS) are associated
with MSS.
The researchers conducted two Cox-proportional hazard analyses on MSS using data from the Melanoma Institute of Australia, an environment with high ultraviolet (UV) radiation (MIA; 5762 melanoma patients; 800 melanoma deaths) and UK Biobank (UKB: 5220 melanoma patients; 241 melanoma deaths) and combined
in a fixed-effect meta-analysis.
In the Leeds melanoma cohort (LMC; 1,947 melanoma patients; Significant outcomes were investigated in 370 melanoma deaths (P < 5 × 10-8).
In addition, the researchers developed a CM susceptibility PRS
using a large independent GWAS meta-analysis (23,913 cases, 342,870 controls).
The relationship
between PRS and MSS was tested in MIA and UKB cohorts.
The results showed that in the meta-analysis of MIA and UKB, two loci were significantly associated with MSS, namely rs41309643 (G allele frequency 1.
6%, HR=2.
09, 95% CI=1.
61-2.
71, P=2.
08×10-8) on chromosome 7 and rs75682113 (C allele frequency 1.
8%, HR=2.
38, 95%CI=1.
77-3.
21, P=1.
07× on chromosome 7 10-8）
。 Although neither SNP was replicated in LMC, rs75682113 was significantly associated
in the merged discovery and replication group.
After adjusting for age, sex, and top ten principal components at diagnosis, an increase of one standard deviation in CM susceptibility PRS was associated with improvement in MSS (HR = 0.
88, 95% CI = 0.
83 to 0.
94, P = 6.
93 × 10-5; I2 = 88%)
.
However, this is only driven by cohorts in high-UV environments (MIA HR = 0.
84, 95% CI = 0.
78-0.
90).
Taken together, the study identified two loci
that may be associated with MSS.
In a high-ultraviolet environment, an increased genetic susceptibility to CM is associated
with improved MSS.
Original source:
Mathias Seviiri, et al.
,Higher polygenic risk for melanoma is associated with improved survival in a high ultraviolet radiation setting .
J Transl Med.
2022 Sep 5; 20(1):403.
doi: 10.
1186/s12967-022-03613-2.
