Sunscreen/ultraviolet protection and non-Hodgkin lymphoma: a Mendelian randomization study_West China Medical Journal

Authors：

ZHAO Xiaoting ,  GAO Xing , LIU Wenling

School of International Nuring, Hainan Medical University, Haikou, Hainan 571199, P. R. China;

Corresponding author：

GAO Xing, Email: 479297163@qq.com

Keywords：

Sunscreen; ultraviolet protection; non-Hodgkin lymphoma; Mendelian randomization study; causal relationship

DOI：

10.7507/1002-0179.202406236

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To analyze the potential causal relationship between sunscreen/ultraviolet protection and the risk of non-Hodgkin lymphoma using a two sample Mendelian randomization (MR) study method. Methods The summary data of genome-wide association study was used to select three types of non-Hodgkin lymphoma, namely diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, T/NK cell lymphoma, and sunscreen/ultraviolet protection highly correlated genetic loci, namely single nucleotide polymorphism (SNP), as instrumental variables. The reverse variance weighting method was used as the main method for MR analysis, MR Egger and MR-PRESO were used to detect level pleiotropy, and leave-one-out method was used for sensitivity analysis to ensure the robustness of the results. Results A total of 132 SNPs were included in the analysis. The results of the inverse variance weighted analysis showed that sunscreen/ultraviolet protection increased the incidence of DLBCL [odds ratio=2.439, 95% confidence interval (1.109, 5.362), P=0.027]. The heterogeneity test results showed that there was no heterogeneity in the causal relationship between sunscreen/ultraviolet protection and DLBCL (P>0.05). The results of the horizontal pleiotropy test showed that SNP did not exhibit horizontal pleiotropy (P>0.05). The leave-one-out method showed that no SNP with a significant impact on the results was found. There was no causal relationship between sunscreen/ultraviolet protection and follicular lymphoma and T/NK cell lymphoma. Conclusion There is a positive causal relationship between sunscreen/ultraviolet protection and the incidence of DLBCL.

1.	Thandra KC, Barsouk A, Saginala K, et al. Epidemiology of non-Hodgkin’s lymphoma. Med Sci (Basel), 2021, 9(1): 5.
2.	Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2024, 74(3): 229-263.
3.	Pudasaini S, Dreyling M. Non-Hodgkin’s lymphomas: a short overview. Inn Med (Heidelb), 2025, 6(3): 290-298.
4.	Mafra A, Laversanne M, Gospodarowicz M, et al. Global patterns of non-Hodgkin lymphoma in 2020. Int J Cancer, 2022, 151(9): 1474-1481.
5.	Miret M, Anderson A, Hindocha P, et al. Incidence of second primary malignancies in relapsed/refractory B-cell non-Hodgkin’s lymphoma patients in England. Leuk Res, 2023, 127: 107042.
6.	Cerhan JR, Slager SL. Familial predisposition and genetic risk factors for lymphoma. Blood, 2015, 126(20): 2265-2273.
7.	Carbone A, Vaccher E, Gloghini A. Hematologic cancers in individuals infected by HIV. Blood, 2022, 139(7): 995-1012.
8.	Gentile G, Arcaini L, Antonelli G, et al. Editorial: HBV and lymphoma. Front Oncol, 2023, 13: 1236816.
9.	Zhang W, Du F, Wang L, et al. Hepatitis virus-associated non-hodgkin lymphoma: pathogenesis and treatment strategies. J Clin Transl Hepatol, 2023, 11(5): 1256-1266.
10.	Bednarska K, Chowdhury R, Tobin JWD, et al. Epstein-Barr virus-associated lymphomas decoded. Br J Haematol, 2024, 204(2): 415-433.
11.	Li H, Zhou J, Zhou L, et al. Identification of the shared gene signatures and molecular pathways in systemic lupus erythematosus and diffuse large B-cell lymphoma. J Gene Med, 2023, 25(12): e3558.
12.	Li H, Yu L, Zhang X, et al. Exploring the molecular mechanisms and shared gene signatures between rheumatoid arthritis and diffuse large B cell lymphoma. Front Immunol, 2022, 13: 1036239.
13.	Zhou Y, Zhang X, Li X, et al. Anthropometric indicators may explain the high incidence of follicular lymphoma in Europeans: results from a bidirectional two-sample two-step Mendelian randomisation. Gene, 2024, 911: 148320.
14.	Cahoon EK, Pfeiffer RM, Wheeler DC, et al. Relationship between ambient ultraviolet radiation and non-Hodgkin lymphoma subtypes: a U. S. population-based study of racial and ethnic groups. Int J Cancer, 2015, 136(5): E432-E441.
15.	Bertrand KA, Chang ET, Abel GA, et al. Sunlight exposure, vitamin D, and risk of non-Hodgkin lymphoma in the Nurses’ Health Study. Cancer Causes Control, 2011, 22(12): 1731-1741.
16.	Petridou ET, Dikalioti SK, Skalkidou A, et al. Sun exposure, birth weight, and childhood lymphomas: a case control study in Greece. Cancer Causes Control, 2007, 18(9): 1031-1037.
17.	Odutola MK, van Leeuwen MT, Bruinsma F, et al. A population-based family case-control study of sun exposure and follicular lymphoma risk. Cancer Epidemiol Biomarkers Prev, 2024, 33(1): 106-116.
18.	Sun C, Liu C, Liu X, et al. Causal relationship between circulating cytokines and follicular lymphoma: a two-sample Mendelian randomization study. Am J Cancer Res, 2024, 14(4): 1577-1593.
19.	Skrivankova VW, Richmond RC, Woolf BAR, et al. Strengthening the reporting of observational studies in epidemiology using mendelian randomization: the STROBE-MR statement. JAMA, 2021, 326(16): 1614-1621.
20.	Chen L, Fan Z, Sun X, et al. Examination on the risk factors of cholangiocarcinoma: a Mendelian randomization study. Front Pharmacol, 2022, 13: 900424.
21.	Zhang Y, Wang M, Li Z, et al. An overview of detecting gene-trait associations by integrating GWAS summary statistics and eQTLs. Sci China Life Sci, 2024, 67(6): 1133-1154.
22.	Haycock PC, Borges MC, Burrows K, et al. Design and quality control of large-scale two-sample Mendelian randomization studies. Int J Epidemiol, 2023, 52(5): 1498-1521.
23.	Papadimitriou N, Dimou N, Tsilidis KK, et al. Physical activity and risks of breast and colorectal cancer: a Mendelian randomisation analysis. Nat Commun, 2020, 11(1): 597.
24.	Mounier N, Kutalik Z. Bias correction for inverse variance weighting Mendelian randomization. Genet Epidemiol, 2023, 47(4): 314-331.
25.	Burgess S, Woolf B, Mason AM, et al. Addressing the credibility crisis in Mendelian randomization. BMC Med, 2024, 22(1): 374.
26.	Abuduxukuer R, Niu PP, Guo ZN, et al. Circulating insulin-like growth factor 1 levels and migraine risk: a Mendelian randomization study. Neurol Ther, 2022, 11(4): 1677-1689.
27.	Yuan S, Kim JH, Xu P, et al. Causal association between celiac disease and inflammatory bowel disease: a two-sample bidirectional Mendelian randomization study. Front Immunol, 2023, 13: 1057253.
28.	Yeung SLA, Luo S, Iwagami M, et al. Introduction to Mendelian randomization. Ann Clin Epidemiol, 2025, 7(1): 27-37.
29.	Wang P, Lin Z, Pan W. Unbiased causal inference with Mendelian randomization and covariate-adjusted GWAS data. HGG Adv, 2025, 6(2): 100412.
30.	Wang SS, Bertrand KA, Deubler EL, et al. Prospective pooled analyses of ambient ultraviolet radiation levels and risk of non-Hodgkin lymphoma and multiple myeloma. Am J Epidemiol, 2024, 24: kwae449.
31.	Little MP, Mai JZ, Fang M, et al. Solar ultraviolet radiation exposure, and incidence of childhood acute lymphocytic leukaemia and non-Hodgkin lymphoma in a US population-based dataset. Br J Cancer, 2024, 130(9): 1441-1452.
32.	Merryman R, Mehtap Ö, LaCasce A. Advancements in the management of follicular lymphoma: a comprehensive review. Turk J Haematol, 2024, 41(2): 69-82.
33.	Han JX, Koh MJ, Boussi L, et al. Global outcomes and prognosis for relapsed/refractory mature T-cell and NK-cell lymphomas: results from the PETAL consortium. Blood Adv, 2025, 9(3): 583-602.
34.	O’Sullivan DE, Hillier TWR, Brenner DR, et al. Time spent in the sun and the risk of developing non-Hodgkin lymphoma: a Canadian cohort study. Cancer Causes Control, 2023, 34(9): 791-799.
35.	Barraclough A, Hawkes E, Sehn LH, et al. Diffuse large B-cell lymphoma. Hematol Oncol, 2024, 42(6): e3202.
36.	Kim HB, Kim JH. Sunlight exposure in association with risk of lymphoid malignancy: a meta-analysis of observational studies. Cancer Causes Control, 2021, 32(5): 441-457.
37.	Nath K, Tomas AA, Flynn J, et al. Vitamin D insufficiency and clinical outcomes with chimeric antigen receptor T-cell therapy in large B-cell lymphoma. Transplant Cell Ther, 2022, 28(11): 751.e1-751.e7.
38.	Adami J, Gridley G, Nyrén O, et al. Sunlight and non-Hodgkin’s lymphoma: a population-based cohort study in Sweden. Int J Cancer, 1999, 80(5): 641-645.
39.	Gao F, Zhang T, Liu H, et al. Risk factors for POD24 in patients with previously untreated follicular lymphoma: a systematic review and meta-analysis. Ann Hematol, 2022, 101(11): 2383-2392.
40.	Garcin LM, Gelot A, Gomez RR, et al. Pigmentary traits, sun exposure, and risk of non-Hodgkin’s lymphoma/chronic lymphocytic leukemia: a study within the French E3N prospective cohort. Cancer Med, 2021, 10(1): 297-304.
41.	Lindqvist PG, Epstein E, Landin-Olsson M. Sun exposure - hazards and benefits. Anticancer Res, 2022, 42(4): 1671-1677.
42.	Tran V, Janda M, Lucas RM, et al. Vitamin D and sun exposure: a community survey in Australia. Curr Oncol, 2023, 30(2): 2465-2481.
43.	Karampinis E, Aloizou AM, Zafiriou E, et al. Non-melanoma skin cancer and vitamin D: The “lost sunlight” paradox and the oxidative stress explanation. Antioxidants (Basel), 2023, 12(5): 1107.
44.	Giovannucci E. The epidemiology of vitamin D and cancer incidence and mortality: a review (United States). Cancer Causes Control, 2005, 16(2): 83-95.
45.	Kricker A, Weber MF, Pawlita M, et al. Cutaneous β HPVs, sun exposure, and risk of squamous and basal cell skin cancers in Australia. Cancer Epidemiol Biomarkers Prev, 2022, 31(3): 614-624.
46.	Neale RE, Lucas RM, Byrne SN, et al. The effects of exposure to solar radiation on human health. Photochem Photobiol Sci, 2023, 22(5): 1011-1047.
47.	祝纤纤, 朱至锴, 姚圣泓, 等. 紫外线照射在疾病发生发展中的作用研究进展. 环境与职业医学, 2023, 40(7): 848-853.

1. Thandra KC, Barsouk A, Saginala K, et al. Epidemiology of non-Hodgkin’s lymphoma. Med Sci (Basel), 2021, 9(1): 5.
2. Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2024, 74(3): 229-263.
3. Pudasaini S, Dreyling M. Non-Hodgkin’s lymphomas: a short overview. Inn Med (Heidelb), 2025, 6(3): 290-298.
4. Mafra A, Laversanne M, Gospodarowicz M, et al. Global patterns of non-Hodgkin lymphoma in 2020. Int J Cancer, 2022, 151(9): 1474-1481.
5. Miret M, Anderson A, Hindocha P, et al. Incidence of second primary malignancies in relapsed/refractory B-cell non-Hodgkin’s lymphoma patients in England. Leuk Res, 2023, 127: 107042.
6. Cerhan JR, Slager SL. Familial predisposition and genetic risk factors for lymphoma. Blood, 2015, 126(20): 2265-2273.
7. Carbone A, Vaccher E, Gloghini A. Hematologic cancers in individuals infected by HIV. Blood, 2022, 139(7): 995-1012.
8. Gentile G, Arcaini L, Antonelli G, et al. Editorial: HBV and lymphoma. Front Oncol, 2023, 13: 1236816.
9. Zhang W, Du F, Wang L, et al. Hepatitis virus-associated non-hodgkin lymphoma: pathogenesis and treatment strategies. J Clin Transl Hepatol, 2023, 11(5): 1256-1266.
10. Bednarska K, Chowdhury R, Tobin JWD, et al. Epstein-Barr virus-associated lymphomas decoded. Br J Haematol, 2024, 204(2): 415-433.
11. Li H, Zhou J, Zhou L, et al. Identification of the shared gene signatures and molecular pathways in systemic lupus erythematosus and diffuse large B-cell lymphoma. J Gene Med, 2023, 25(12): e3558.
12. Li H, Yu L, Zhang X, et al. Exploring the molecular mechanisms and shared gene signatures between rheumatoid arthritis and diffuse large B cell lymphoma. Front Immunol, 2022, 13: 1036239.
13. Zhou Y, Zhang X, Li X, et al. Anthropometric indicators may explain the high incidence of follicular lymphoma in Europeans: results from a bidirectional two-sample two-step Mendelian randomisation. Gene, 2024, 911: 148320.
14. Cahoon EK, Pfeiffer RM, Wheeler DC, et al. Relationship between ambient ultraviolet radiation and non-Hodgkin lymphoma subtypes: a U. S. population-based study of racial and ethnic groups. Int J Cancer, 2015, 136(5): E432-E441.
15. Bertrand KA, Chang ET, Abel GA, et al. Sunlight exposure, vitamin D, and risk of non-Hodgkin lymphoma in the Nurses’ Health Study. Cancer Causes Control, 2011, 22(12): 1731-1741.
16. Petridou ET, Dikalioti SK, Skalkidou A, et al. Sun exposure, birth weight, and childhood lymphomas: a case control study in Greece. Cancer Causes Control, 2007, 18(9): 1031-1037.
17. Odutola MK, van Leeuwen MT, Bruinsma F, et al. A population-based family case-control study of sun exposure and follicular lymphoma risk. Cancer Epidemiol Biomarkers Prev, 2024, 33(1): 106-116.
18. Sun C, Liu C, Liu X, et al. Causal relationship between circulating cytokines and follicular lymphoma: a two-sample Mendelian randomization study. Am J Cancer Res, 2024, 14(4): 1577-1593.
19. Skrivankova VW, Richmond RC, Woolf BAR, et al. Strengthening the reporting of observational studies in epidemiology using mendelian randomization: the STROBE-MR statement. JAMA, 2021, 326(16): 1614-1621.
20. Chen L, Fan Z, Sun X, et al. Examination on the risk factors of cholangiocarcinoma: a Mendelian randomization study. Front Pharmacol, 2022, 13: 900424.
21. Zhang Y, Wang M, Li Z, et al. An overview of detecting gene-trait associations by integrating GWAS summary statistics and eQTLs. Sci China Life Sci, 2024, 67(6): 1133-1154.
22. Haycock PC, Borges MC, Burrows K, et al. Design and quality control of large-scale two-sample Mendelian randomization studies. Int J Epidemiol, 2023, 52(5): 1498-1521.
23. Papadimitriou N, Dimou N, Tsilidis KK, et al. Physical activity and risks of breast and colorectal cancer: a Mendelian randomisation analysis. Nat Commun, 2020, 11(1): 597.
24. Mounier N, Kutalik Z. Bias correction for inverse variance weighting Mendelian randomization. Genet Epidemiol, 2023, 47(4): 314-331.
25. Burgess S, Woolf B, Mason AM, et al. Addressing the credibility crisis in Mendelian randomization. BMC Med, 2024, 22(1): 374.
26. Abuduxukuer R, Niu PP, Guo ZN, et al. Circulating insulin-like growth factor 1 levels and migraine risk: a Mendelian randomization study. Neurol Ther, 2022, 11(4): 1677-1689.
27. Yuan S, Kim JH, Xu P, et al. Causal association between celiac disease and inflammatory bowel disease: a two-sample bidirectional Mendelian randomization study. Front Immunol, 2023, 13: 1057253.
28. Yeung SLA, Luo S, Iwagami M, et al. Introduction to Mendelian randomization. Ann Clin Epidemiol, 2025, 7(1): 27-37.
29. Wang P, Lin Z, Pan W. Unbiased causal inference with Mendelian randomization and covariate-adjusted GWAS data. HGG Adv, 2025, 6(2): 100412.
30. Wang SS, Bertrand KA, Deubler EL, et al. Prospective pooled analyses of ambient ultraviolet radiation levels and risk of non-Hodgkin lymphoma and multiple myeloma. Am J Epidemiol, 2024, 24: kwae449.
31. Little MP, Mai JZ, Fang M, et al. Solar ultraviolet radiation exposure, and incidence of childhood acute lymphocytic leukaemia and non-Hodgkin lymphoma in a US population-based dataset. Br J Cancer, 2024, 130(9): 1441-1452.
32. Merryman R, Mehtap Ö, LaCasce A. Advancements in the management of follicular lymphoma: a comprehensive review. Turk J Haematol, 2024, 41(2): 69-82.
33. Han JX, Koh MJ, Boussi L, et al. Global outcomes and prognosis for relapsed/refractory mature T-cell and NK-cell lymphomas: results from the PETAL consortium. Blood Adv, 2025, 9(3): 583-602.
34. O’Sullivan DE, Hillier TWR, Brenner DR, et al. Time spent in the sun and the risk of developing non-Hodgkin lymphoma: a Canadian cohort study. Cancer Causes Control, 2023, 34(9): 791-799.
35. Barraclough A, Hawkes E, Sehn LH, et al. Diffuse large B-cell lymphoma. Hematol Oncol, 2024, 42(6): e3202.
36. Kim HB, Kim JH. Sunlight exposure in association with risk of lymphoid malignancy: a meta-analysis of observational studies. Cancer Causes Control, 2021, 32(5): 441-457.
37. Nath K, Tomas AA, Flynn J, et al. Vitamin D insufficiency and clinical outcomes with chimeric antigen receptor T-cell therapy in large B-cell lymphoma. Transplant Cell Ther, 2022, 28(11): 751.e1-751.e7.
38. Adami J, Gridley G, Nyrén O, et al. Sunlight and non-Hodgkin’s lymphoma: a population-based cohort study in Sweden. Int J Cancer, 1999, 80(5): 641-645.
39. Gao F, Zhang T, Liu H, et al. Risk factors for POD24 in patients with previously untreated follicular lymphoma: a systematic review and meta-analysis. Ann Hematol, 2022, 101(11): 2383-2392.
40. Garcin LM, Gelot A, Gomez RR, et al. Pigmentary traits, sun exposure, and risk of non-Hodgkin’s lymphoma/chronic lymphocytic leukemia: a study within the French E3N prospective cohort. Cancer Med, 2021, 10(1): 297-304.
41. Lindqvist PG, Epstein E, Landin-Olsson M. Sun exposure - hazards and benefits. Anticancer Res, 2022, 42(4): 1671-1677.
42. Tran V, Janda M, Lucas RM, et al. Vitamin D and sun exposure: a community survey in Australia. Curr Oncol, 2023, 30(2): 2465-2481.
43. Karampinis E, Aloizou AM, Zafiriou E, et al. Non-melanoma skin cancer and vitamin D: The “lost sunlight” paradox and the oxidative stress explanation. Antioxidants (Basel), 2023, 12(5): 1107.
44. Giovannucci E. The epidemiology of vitamin D and cancer incidence and mortality: a review (United States). Cancer Causes Control, 2005, 16(2): 83-95.
45. Kricker A, Weber MF, Pawlita M, et al. Cutaneous β HPVs, sun exposure, and risk of squamous and basal cell skin cancers in Australia. Cancer Epidemiol Biomarkers Prev, 2022, 31(3): 614-624.
46. Neale RE, Lucas RM, Byrne SN, et al. The effects of exposure to solar radiation on human health. Photochem Photobiol Sci, 2023, 22(5): 1011-1047.
47. 祝纤纤, 朱至锴, 姚圣泓, 等. 紫外线照射在疾病发生发展中的作用研究进展. 环境与职业医学, 2023, 40(7): 848-853.

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