Evidence for a Causal Relationship Between Psoriasis and Cutaneous Melanoma: a Bidirectional Two-sample Mendelian Randomized Study

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2023 Jul 28

PMID 37503344

Authors

Nana Zhao

Pengsen Guo

Mei Tang

Fan Yang

Tongtong Zhang

Rui Mao

Affiliations

Soon will be listed here.

Abstract

Background And Objective: Existing cross-sectional and retrospective studies were unable to establish a causal relationship between psoriasis and cutaneous melanoma (CM). We sought to evaluate the causal role between psoriasis and CM.

Methods: We performed a bidirectional two-sample Mendelian randomization analysis using summary statistics from genome-wide association studies of psoriasis and CM among individuals of predominantly European ancestry. Mendelian randomization-Egger regression, inverse variance weighting, Mendelian Randomization Pleiotropy RESidual Sum and Outlier, weighted mode, and weighted median were used to examine the causal effect between psoriasis and CM.

Results: Genetically predicted psoriasis was a significant risk factor for CM (odds ratio, 1.69; 95% confidence interval, 1.15-2.48; P = 0.025). In contrast, no association was observed between genetically predicted CM and psoriasis.

Conclusion: Our findings corroborated the existence of genetically predicted psoriasis increases risk of CM. Enhanced early screening of cutaneous melanoma in patients with psoriasis may improve clinical burden. However, we did not find evidence for a causal link from CM to psoriasis, so further studies are required to elucidate the effect of CM activity on psoriasis.

Citing Articles

Basophils may as a risk factor for upper gastrointestinal cancer: a Mendelian randomization (MR) study.

Nov P, Li W, Wang D, Touch S, Kouy S, Ni P Ecancermedicalscience. 2025; 18():1799.

PMID: 39816393 PMC: 11735140. DOI: 10.3332/ecancer.2024.1799.

The causal relationship between immune cells and hepatocellular carcinoma: a Mendelian randomization (MR).

Nov P, Zhang Y, Wang D, Sou S, Touch S, Kouy S Ecancermedicalscience. 2025; 18():1794.

PMID: 39816386 PMC: 11735144. DOI: 10.3332/ecancer.2024.1794.

Genetically Predicted Peripheral Immune Cells Mediate the Effect of Gut Microbiota on Influenza Susceptibility.

Wang S, Ou G, Wu J, Chen Y, Xu L, Xu H Int J Mol Sci. 2024; 25(14).

PMID: 39062949 PMC: 11276963. DOI: 10.3390/ijms25147706.

Dietary Factors and Risk of Gout: A Two-Sample Mendelian Randomization Study.

Ou G, Wu J, Wang S, Jiang Y, Chen Y, Kong J Foods. 2024; 13(8).

PMID: 38672942 PMC: 11049247. DOI: 10.3390/foods13081269.

Causal relationships between CD25 on immune cells and hip osteoarthritis.

Luo H, Zhu Y, Guo B, Ruan Z, Liu Z, Fan Z Front Immunol. 2023; 14:1247710.

PMID: 37731506 PMC: 10507251. DOI: 10.3389/fimmu.2023.1247710.

References

Hinz M, Krappmann D, Eichten A, Heder A, Scheidereit C, Strauss M . NF-kappaB function in growth control: regulation of cyclin D1 expression and G0/G1-to-S-phase transition. Mol Cell Biol. 1999; 19(4):2690-8. PMC: 84062. DOI: 10.1128/MCB.19.4.2690. View

Chan I, Kwok M, Schooling C . Blood pressure and risk of cancer: a Mendelian randomization study. BMC Cancer. 2021; 21(1):1338. PMC: 8675492. DOI: 10.1186/s12885-021-09067-x. View

Margolis D, Bilker W, Hennessy S, VITTORIO C, SANTANNA J, Strom B . The risk of malignancy associated with psoriasis. Arch Dermatol. 2001; 137(6):778-83. View

Dusingize J, Olsen C, An J, Pandeya N, Law M, Thompson B . Body mass index and height and risk of cutaneous melanoma: Mendelian randomization analyses. Int J Epidemiol. 2020; 49(4):1236-1245. PMC: 7778056. DOI: 10.1093/ije/dyaa009. View

Moore R, Owens D, Stamp G, Arnott C, Burke F, East N . Mice deficient in tumor necrosis factor-alpha are resistant to skin carcinogenesis. Nat Med. 1999; 5(7):828-31. DOI: 10.1038/10552. View

Senftleben U, Cao Y, Xiao G, Greten F, Krahn G, Bonizzi G . Activation by IKKalpha of a second, evolutionary conserved, NF-kappa B signaling pathway. Science. 2001; 293(5534):1495-9. DOI: 10.1126/science.1062677. View

Elwood J, Gallagher R, Stapleton P . No association between malignant melanoma and acne or psoriasis: results from the Western Canada Melanoma Study. Br J Dermatol. 1986; 115(5):573-6. DOI: 10.1111/j.1365-2133.1986.tb05767.x. View

Stern R . The risk of melanoma in association with long-term exposure to PUVA. J Am Acad Dermatol. 2001; 44(5):755-61. DOI: 10.1067/mjd.2001.114576. View

Egeberg A, Thyssen J, Gislason G, Skov L . Skin cancer in patients with psoriasis. J Eur Acad Dermatol Venereol. 2016; 30(8):1349-53. DOI: 10.1111/jdv.13619. View

10.

Guttridge D, Albanese C, Reuther J, Pestell R, Baldwin Jr A . NF-kappaB controls cell growth and differentiation through transcriptional regulation of cyclin D1. Mol Cell Biol. 1999; 19(8):5785-99. PMC: 84428. DOI: 10.1128/MCB.19.8.5785. View

11.

Burgess S . Sample size and power calculations in Mendelian randomization with a single instrumental variable and a binary outcome. Int J Epidemiol. 2014; 43(3):922-9. PMC: 4052137. DOI: 10.1093/ije/dyu005. View

12.

Chan K, Sano S, Kiguchi K, Anders J, Komazawa N, Takeda J . Disruption of Stat3 reveals a critical role in both the initiation and the promotion stages of epithelial carcinogenesis. J Clin Invest. 2004; 114(5):720-8. PMC: 514583. DOI: 10.1172/JCI21032. View

13.

Devergne O, Hatzivassiliou E, Izumi K, Kaye K, Kleijnen M, Kieff E . Association of TRAF1, TRAF2, and TRAF3 with an Epstein-Barr virus LMP1 domain important for B-lymphocyte transformation: role in NF-kappaB activation. Mol Cell Biol. 1996; 16(12):7098-108. PMC: 231713. DOI: 10.1128/MCB.16.12.7098. View

14.

Koo J . Systemic sequential therapy of psoriasis: a new paradigm for improved therapeutic results. J Am Acad Dermatol. 1999; 41(3 Pt 2):S25-8. DOI: 10.1016/s0190-9622(99)70363-4. View

15.

Patel R, Clark L, Lebwohl M, Weinberg J . Treatments for psoriasis and the risk of malignancy. J Am Acad Dermatol. 2009; 60(6):1001-17. DOI: 10.1016/j.jaad.2008.12.031. View

16.

Polesie S, Gillstedt M . Psoriasis and risk of cutaneous melanoma: A retrospective, comparative, registry-based cohort study. J Am Acad Dermatol. 2021; 86(1):215-217. DOI: 10.1016/j.jaad.2021.01.084. View

17.

Huang S, Deguzman A, Bucana C, Fidler I . Nuclear factor-kappaB activity correlates with growth, angiogenesis, and metastasis of human melanoma cells in nude mice. Clin Cancer Res. 2000; 6(6):2573-81. View

18.

Budu-Aggrey A, Brumpton B, Tyrrell J, Watkins S, Modalsli E, Celis-Morales C . Evidence of a causal relationship between body mass index and psoriasis: A mendelian randomization study. PLoS Med. 2019; 16(1):e1002739. PMC: 6354959. DOI: 10.1371/journal.pmed.1002739. View

19.

Reddy S, Martires K, Wu J . The risk of melanoma and hematologic cancers in patients with psoriasis. J Am Acad Dermatol. 2016; 76(4):639-647.e2. DOI: 10.1016/j.jaad.2016.09.047. View

20.

Stern R, Nichols K, Vakeva L . Malignant melanoma in patients treated for psoriasis with methoxsalen (psoralen) and ultraviolet A radiation (PUVA). The PUVA Follow-Up Study. N Engl J Med. 1997; 336(15):1041-5. DOI: 10.1056/NEJM199704103361501. View