Arsenic exposure and risk of skin cancer (melanoma and non-melanoma): a systematic review and meta-analysis

He, Lijiao; Wei, Meiying; Yang, Qikui; Huang, Yun; Wei, Zuyuan

doi:10.1016/j.abd.2025.501161

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Original Article • An. Bras. Dermatol. 100 (05) • 2025 • https://doi.org/10.1016/j.abd.2025.501161 linkcopy

Arsenic exposure and risk of skin cancer (melanoma and non-melanoma): a systematic review and meta-analysis

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Background Arsenic, recognized as a potentially lethal substance and a carcinogen, has been associated with an increased risk of skin cancer; however, the findings have been inconsistent. The aim of this study was to assess the impact of arsenic exposure on skin cancer risk (including melanoma and non-melanoma) through a meta-analysis of the available data.

Objectives To assess the risk of skin cancer from arsenic exposure.

Methods Searches were performed in databases such as PubMed, Web of Science, Embase, and CNKI (as of June 10, 2024). The pooled odds ratio (OR) and its 95% Confidence Interval (95% CI) were calculated using a random effects model. Subgroup analyses were performed considering sample size, study centers, U.S. regions, arsenic exposure routes, and measurement methods.

Results A total of 12 papers were included, comprising 48,003 participants. The findings indicated an association between arsenic exposure and the risk of skin cancer ([OR = 1.51], 95% CI 1.26-1.80). Specifically, the OR was 1.52 (95% CI 1.06-2.17) for melanoma, 1.64 (95% CI 1.16-2.32) for squamous cell carcinoma, and 1.36 (95% CI 1.04-1.77) for basal cell carcinoma. Subgroup analyses also revealed an association between arsenic exposure and skin cancer in the United States (OR = 1.52, 95% CI 1.25-1.87). Both ingestion and inhalation pathways of arsenic exposure showed a trend toward an increased risk of skin cancer.

Study limitations An important limitation of this study is a degree of heterogeneity, and another is due to the limited number of research papers available.

Conclusion This meta-analysis indicates that arsenic exposure may be associated with an elevated risk of skin cancer. Additional prospective research is necessary to verify the association between arsenic exposure and the incidence of skin cancer, encompassing both cutaneous malignant melanoma and non-melanoma skin cancer.

Keywords
Arsenic; Basal cell carcinoma; Melanoma; Meta-analysis; Squamous cell carcinoma; Systematic review

First author	Year	Research type	Author states	Sample (n)		Age (year)		Sex (Male/ Female)		Definitions of arsenic exposure	Follow-up (years)	Skin cancer type
First author	Year	Research type	Author states	Skin cancer	Non-skin cancer	Skin cancer	Non-skin cancer	Skin cancer	Non-skin cancer	Definitions of arsenic exposure	Follow-up (years)	Skin cancer type
Bedaiwi ³³	2022	Case-control study	USA	Melanoma (87)	Non-skin cancer (12615)	64.6	45.4	M: 51.7% / F: 44.7%	M: 50.0% / F: 50.0%	Urine As concentration (>50ug/L)	NA	Melanoma
Langston ³⁴	2022	Case-control study	USA	Melanoma (1096)	Non-skin cancer (1033)	20‒39: 13% 40‒49: 14% 50‒59: 21% 60‒69: 23% 70‒79: 18% 80+: 11%	20‒39: 17% 40‒49: 15% 50‒59: 25% 60‒69: 26% 70‒79: 13% 80+: 4%	M: 52% / F: 48%	M: 45% / F: 55%	Drinking water As (>10ug/L)	NA	Melanoma
Beane Freeman ³⁵	2004	Case-control study	USA	Melanoma (326)	Non-skin cancer (329)	40‒49: 26% 50‒59: 22.8% 60‒69: 23.1% 70‒79: 19.6% 80‒89: 8.4%	40‒49: 15.8% 50‒59: 29.8% 60‒69: 28.4% 70‒79: 18.2% 80‒89: 7.8%	M: 55.7% / F: 44.3%	M: 64.3% / F: 35.7%	Toenails As concentration (>0.084 ug/g)	NA	Melanoma
Collatuzzo ³⁶	2023	Case-control study	Italy	Melanoma (295)	Non-skin cancer (293)	<35: 14.8% 35‒49: 27.6% 50‒64: 3.2% ≥65: 24.3%	<35: 20% 35‒49:25.2% 50‒64: 31.2% ≥65: 23.6%	M: 47% / F: 53%	M: 47.2% / F: 52.8%	Occupational exposure to As (undefined)	NA	Melanoma
Dennis ³⁷	2010	Cohort study	USA	Melanoma (150)	Non-skin cancer (24554)	57	48	NA	NA	Arsenical pesticide exposure	10.3 years	Melanoma
Kennedy-1 ²²	2005	Case-control study	Netherlands	Melanoma (47)	Non-skin cancer (164)	NA	NA	NA	NA	Occupational exposure to As(undefined)	NA	Melanoma
Kennedy-2 ²²	2005	Case-control study	Netherlands	Basal cell carcinoma (249)	Non-skin cancer (164)	NA	NA	NA	NA	Occupational exposure to As (undefined)	NA	Basal cell carcinoma
Kennedy-3 ²²	2005	Case-control study	Netherlands	Squamous cell carcinoma (103)	Non-skin cancer (164)	NA	NA	NA	NA	Occupational exposure to As (undefined)	NA	Squamous cell carcinoma
Surdu-1 ²³	2013	Case-control study	USA	Basal cell carcinoma (500)	Non-skin cancer (515)	67	61	M: 44.8% / F: 55.2%	M: 51.6% / F: 48.4%	Occupational exposure to As (dust fumes)	NA	Basal cell carcinoma
Surdu-2 ²³	2013	Case-control study	USA	Squamous cell carcinoma (70)	Non-skin cancer (515)	71.5	61	M: 54.3% / F: 45.7%	M: 51.6% / F: 48.4%	Occupational exposure to As (dust fumes)	NA	Squamous cell carcinoma
Mitropoulos ²⁴	2004	Case-control study	USA	Squamous cell carcinoma (404)	Non-skin cancer (395)	NA	NA	NA	NA	Occupational exposure to As (undefined)	NA	Squamous cell carcinoma
Sánchez ²⁵	2013	Case-control study	Colombia	Squamous cell carcinoma (166)	Non-skin cancer (166)	70.8	71.8	M: 31% / F: 69%	M:31% / F: 69%	Occupational exposure to As (carpentry trade wood, gunpowder, metal industries)	NA	Squamous cell carcinoma
Suárez-1 ²⁶	2007	Case-control study	France	Basal cell carcinoma (1333)	Non-skin cancer (1507)	60.5	58.2	M: 63% / F: 37%	M: 62% / F: 38%	Occupational exposure to As (Agricultural works)	NA	Basal cell carcinoma
Suárez-2 ²⁶	2007	Case-control study	France	Squamous cell carcinoma (183)	Non-skin cancer (1507)	60.5	58.2	M: 63% / F: 37%	M: 62% / F: 38%	Occupational exposure to As (Agricultural works)	NA	Squamous cell carcinoma
Karagas-1 ²⁷	2001	Case-control study	USA	Basal cell carcinoma (587)	Non-skin cancer (524)	<40: 7.2% 40‒49:17% 50‒59:21% 60‒69:34.9% ≥70:19.9%	<40: 5.3% 40‒49:12.6% 50‒59:19.7% 60-69:39.3% ≥70:23.1%	M: 57.6% / F: 42.2%	M: 60.1% / F: 39.9%	Toenails As concentration (0.345-0.81 ug/g)	NA	Basal cell carcinoma
Karagas-2 ²⁷	2001	Case-control study	USA	Squamous cell carcinoma (284)	Non-skin cancer (524)	<40: 1.1% 40‒49:6 % 50‒59: 16.6% 60‒69: 40.9% ≥70: 35.6%	<40:5.3% 40‒49: 12.6% 50‒59: 19.7% 60‒69: 39.3% ≥70: 23.1%	M: 64.1% / F: 35.9%	M: 60.1% / F: 39.9%	Toenails As concentration (0.345-0.81 ug/g)	NA	Squamous cell carcinoma
Gilbert-Diamond ²⁸	2013	Case-control study	USA	Squamous cell carcinoma (470)	Non-skin cancer (447)	<50:4% 50‒59: 19.4% 60‒69: 45.3% ≥70: 31.3%	<50: 7.6% 50‒59: 18.6% 60‒69: 45.4% ≥70: 28.4%	M: 60.4% / F: 39.6%	M: 57.7% / F: 42.3%	Urine As concentration >5.31 ug/L)	NA	Squamous cell carcinoma

Study	Selection				Comparability	Outcomes			Total
Study	1	2	3	4	Comparability	1	2	3	Total
Ahmed Bedaiwi	★	★	★		★	★	★	★	7
Marvin E. Langston	★	★	★		★	★	★	★	7
Laura E. Beane Freeman	★	★	★		★	★	★	★	7
Giulia Collatuzzo	★	★	★		★		★	★	6
Leslie K. Dennis	★	★	★		★		★		5
Cornelis Kennedy	★	★	★		★		★	★	6
Simona Surdu	★	★	★		★		★	★	6
Panagiotis Mitropoulos	★	★	★		★		★	★	6
Guillermo Sánchez	★	★	★		★		★		5
Berta Suárez	★	★	★		★		★	★	6
Margaret R. Karagas	★	★	★		★	★	★	★	7
Diane Gilbert-Diamond	★	★	★		★	★	★	★	7

Subgroup	Study	OR (95% CI)	p-value	I²
USA
Melanoma	3	1.35 (1.10, 1.65)	0.004	65.1
Basal cell carcinoma	2	1.58 (1.19, 2.11)	0.002	0
Squamous cell carcinoma	4	1.54 (1.18, 2.01)	p=0.001	47.8
Sample size
< 100	3	1.64 (1.15, 2.23)	0.006	64.6
> 100	9	1.46 (1.23, 1.72)	p<0.001	35.8
Exposure route
Cconsume	5	1.33 (1.07, 1.64)	0.233	26.9
Inhalation	7	1.72 (1.30, 2.27)	0.034	48.7
Research centre
Single centre	8	1.41 (1.09, 1.82)	0.009	26.3
Multicentre	4	1.61 (1.24, 2.11)	p<0.001	42.6
Measurement method
biomarker	5	1.33 (1.07, 1.64)	0.233	26.9
Occupational assessment semi-definable scale	5	1.80 (1.34, 2.42)	0.061	46.3

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