Table 2.
Summary of epidemiological case-control and cohort studies on skin cancer in humans in relation to ingested arsenic exposure, with emphasis on non-melanoma skin cancers
| Reference | Study Population | Endpoint (Diagnosis Years) | Arsenical Exposure Assessment (Range) | Cohort size (No. of Cases) or No. of cases, No. of controls | Study Results | Comments | ||
|---|---|---|---|---|---|---|---|---|
| Case-control studies | ||||||||
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| ||||||||
| Gilbert-Diamond et al, 2013 | United States (New Hampshire) | Histologically confirmed incident SCC (2003–2009) | Urine (iAs, MMA, DMA) Median ΣAs=4.76 (2.94–8.10) μg/L |
470 invasive SCC, 447 control | OR (95% CI) | Logistic regression analyses; Matched on sex and age; Adjusted for urinary creatinine, sex, age, BMI, education, smoking, skin reaction to chronic sun exposure (excluded participants who consumed seafood 2 days prior to urine collection); Association strongest for MMA; |
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| ln(ΣAs) | 1.37 (1.04, 1.80) | |||||||
| ln(iAs) | 1.20 (0.97, 1.49) | |||||||
| ln(MMA) | 1.34 (1.04, 1.71) | |||||||
| ln(DMA) | 1.34 (1.03, 1.74) | |||||||
|
| ||||||||
| Leonardi et al, 2012 | Hungary, Romania, and Slovakia (ASHRAM study) | Histologically confirmed, consecutively diagnosed BCC (2003–2004) | Water Median iAs=1.2 (0.7–13.8) μg/L |
529 BCC, 540 controls | OR (95% CI) | Matched on sex, age, and area of residence; Adjusted for sex, age, education, area of residence, skin response to 1 hour of midday sun, skin complexion; For each 10 μg/L increase in iAs concentration; |
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| peak daily iAs dose rate | 1.13 (1.07, 1.20) | |||||||
| cumulative iAs dose | 1.10 (1.01, 1.19) | |||||||
| lifetime average water iAs concentration | 1.18 (1.08, 1.28) | |||||||
|
| ||||||||
| Rosales-Castillo et al, 2004 | Mexico (region Lagunera) | Prevalent, clinically diagnosed NMSC | Urine Mean As=34.7 (range=3.2–124.5) μg/L Cumulative As geometric mean=769 (256–11,698) ppm-years |
42 NMSC, 48 controls | OR (P value) | Adjusted for sex, age, sun exposure; Association modified by HPV infection; Arsenic exposure measured as cumulative exposure determined by extrapolating a measurement of current arsenic in urine and participant’s residential history; |
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| Urinary As | 1.01 (0.180) | |||||||
| Cumulative As (HPV-) | 4.53 (0.11) | |||||||
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| Chen et al, 2003 | Southwest Taiwan | Pathologically diagnosed, incident skin cancer (1996–1999) | Urine Mean total As=43.71 (standard deviation=29.34) μg/L Cumulative As mean=8.14 (standard deviation=15.48) mg/L-year |
76 NMSC - 29.2% BD, 33.3% BCC, 47.2% SCC; 224 controls | mg/L-year | OR (95% CI) | Adjusted for sex, age, BMI, education, smoking, hair dye use; Association modified by primary and secondary arsenic methylation index; Cumulative arsenic exposure determined using artesian well water As concentration and duration of drinking artesian well water; |
|
| 0–2 | 1.00 (reference) | |||||||
| >2–15 | 1.87 (0.79–4.45) | |||||||
| >15 | 2.99 (1.30–6.87) | |||||||
| P for trend=0.007 | ||||||||
|
| ||||||||
| Ranft et al, 2003 | Slovakia (Prievidza district) | Histologically confirmed, first NMSC diagnosis (1996–1999) | Urine (iAs, MMA, DMA) Median ΣAs=6.04 (range=1–4) μg/L |
264 NMSC - 91% BCC, Pesch et al, 2002; 286 controls | Ratio of means (P value) | Step-wise regressions; Matched on sex and age; Adjusted for As in house dust samples, As in soil samples, urinary creatinine, sex, age, area of residence, self-supply with homegrown food, smoking, renal disorder; Arsenic exposure primarily from residential proximity to a coal-burning power plant; |
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| ΣAs | 1.12 (0.03) | |||||||
| iAs | 1.13 (0.001) | |||||||
| DMA | 1.21 (0.045) | |||||||
|
| ||||||||
| Karagas et al, 2001 Karagas et al, 2002 |
United States (New Hampshire) | Histologically confirmed incident BCC and SCC (1993–1995) | Toenails Geometric mean=0.094 (range=0.01–0.81) μg/g |
587 BCC, 284 invasive SCC - BD excluded, 524 controls | OR (95% CI) | Matched on sex and age; Point at which dose-response increased for SCC as calculated with a two-segment linear model for BCC and SCC (maximum likelihood change point)=0.105 μg/g (95% CI=0.093, 0.219); |
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| μg/g | BCC | SCC | ||||||
| 0.009–0.089 | 1.00 (reference) | 1.00 (reference) | ||||||
| 0.090–0.133 | 1.01 (0.76, 1.35) | 0.93 (0.64, 1.34) | ||||||
| 0.134–0.211 | 1.06 (0.74, 1.51) | 0.98 (0.61, 1.58) | ||||||
| 0.212–0.280 | 0.72 (0.40, 1.31) | 1.10 (0.55, 2.21) | ||||||
| 0.281–0.344 | 0.75 (0.31, 1.81) | 1.00 (0.33, 3.01) | ||||||
| 0.345–0.81 | 1.44 (0.74, 2.81) | 2.07 (0.92, 4.66) | ||||||
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| Hsueh et al, 1995 | Southwest Taiwan (Homei, Fuhsin, and Hsinming villages in Putai township) | Prevalent skin cancer (90% BD, and 91% BCC and SCC histologically confirmed) (1988–1989) | Water median range=0.70–0.93 ppm (Kuo, 1994) |
1,081 persons (66 skin cancer cases, including BD) | Adjusted for sex and age; Some missing data regarding arsenic exposure; |
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| Average arsenic exposure (ppm): | Cases: | OR (95% CI): | ||||||
| 0 | 2 | 1.00 (reference) | ||||||
| 0.0–0.70 | 20 | 3.45 (0.70–17.0) | ||||||
| >0.71 | 30 | 5.04 (1.07–23.8) | ||||||
| P for trend | <0.05 | |||||||
| Cumulative arsenic exposure (ppm-years) | ||||||||
| <4 | 1 | 1.00 (reference) | ||||||
| 5–24 | 22 | 8.90 (1.07–73.75) | ||||||
| >25 | 28 | 13.74 (1.69–111.64) | ||||||
| P for trend | <0.05 | |||||||
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| Cohort Studies | ||||||||
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| Baastrup et al, 2008 | Denmark (EPIC cohort) | First NMSC diagnosis (1993–2003) | Water mean=1.2 (0.05–25.3) μg/L |
56,378 persons (1,010 NMSC cases) | Time weighted average arsenic levels IRR=0.99 (95% CI=0.94–1.06) | Adjusted for education, occupation, area of enrollment, skin reaction to sun, suntanned during summer; Exposure assigned based on place of residence, and included average concentrations across utilities for some individuals; Few subjects had exposure levels above 2 μg/L; No designation of histologic type (most could be BCC, but BCC and SCC grouped as single outcome), and complete coverage of NMSCs is questionable; |
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| Hsueh et al, 1997 | Southwest Taiwan (Homei, Fuhsin, and Hsinming villages in Putai township) | Incident skin cancer (1989–1992) | Water | 654 persons (33 skin cancer cases, including BD) | Cox proportional hazards analysis; Matched on sex and age; Adjusted for educational; |
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| Average arsenic concentration in drinking water (μg/L): | Cases: | Relative Risk (95% CI): | ||||||
| 0 | 1 | 1.00 (reference) | ||||||
| 10–700 | 12 | 3.30 (0.42, 35.76) | ||||||
| 710–1100 | 13 | 8.69 (1.08, 65.50) | ||||||
| Unknown | 7 | 4.75 (0.55, 40.35) | ||||||
| Cumulative arsenic exposure (μg/L-year): | ||||||||
| 0 | 1 | 1.00 (reference) | ||||||
| 100–10,600 | 2 | 2.82 (0.25, 31.87) | ||||||
| 10,700–17,700 | 5 | 2.61 (0.30, 22.90) | ||||||
| >17,700 | 18 | 7.58 (0.95, 60.33) | ||||||
| Unknown | 7 | 5.14 (0.59, 44.41) | ||||||
OR, odds ratio; CI, confidence interval; NMSC, non-melanoma skin cancer; SCC, squamous cell carcinoma; BCC, basal cell carcinoma; BD, Bowen’s disease; As, arsenic; iAs, inorganic arsenic; MMA, monomethylarsonic acid; DMA, dimethylarsinic acid; ΣAs, total arsenic summed from iAs, MMA and DMA.