Friend or Foe? The Current Epidemiologic Evidence on Selenium and Human Cancer Risk

Figures & data

Figure 1 Number of publications per year yielded a Medline search using the terms “selenium” and “cancer” (solid line) and “selenium,” “cancer,” and “humans” (dotted line).

Table 1 Median Values (μg/l) of Se Chemical Species Identified in Blood (Serum) and Cerebrospinal Fluid (CSF) of 24 Human Subjects, with Their Squared Correlation Coefficients (r²) (Published and Unpublished Data from Solovyev, Berthele, and Michalke [32])

Se Species	Serum	CSF	r^2
Se-cysteine	<LoD^1	<LoD
Selenoprotein P	5.19	0.474	0.037
Glutathione peroxidase	4.27	0.036	0.384
Se-methionine	0.23	<LoD
Thioredoxin reductase	1.64	0.035	0.629
Human serum albumin Se (HSA-Se)	18.03	0.068	0.172
Selenite	12.25	0.046	0.040
Selenate	<LoD	<LoD	0.009
UF^2–1	<LoD	<LoD
UF-2	<LoD	<LoD
UF-3	<LoD	<LoD
UF-4	6.34	<LoD
Total	58.39	0.861	0.0002
^1Limit of detection.
^2Unknown form.

Table 2 Summary of Effect of Se Supplementation on Human Cancer Risk by Cancer Site (Dose of 200 μg/Day as Organic Se When Not Otherwise Specified)

					Selenium
			Placebo		Supplementation
			Group		Group
								95% Confidence
Outcome	Study	Population	Events	Total	Events	Total	RR^a	Interval
Any cancer
NPC	Clark et al., 1996 [102]	Patients with history of basal or squamous cell skin cancer	119	659	77	653	0.63	(0.47–0.85)
NPC	Duffield-Lillico et al., 2002 [93]	Patients with history of basal or squamous cell skin cancer	137	629	105	621	0.75	(0.58–0.97)
NPC	Reid et al., 2008 [123]	Patients with history of basal or squamous cell skin cancer	21	161	15	154	0.73	(0.35–1.48)
NPC	Reid et al., 2008 (400mcg/day Se) [123]	Patients with history of basal or squamous cell skin cancer	19	213	21	210	1.10	(0.57–2.17)
SELECT	Lippman et al., 2009 [99]	>50 yrs. men not at risk for prostate cancer, US, Canada and Puerto Rico	824	8696	837	8752	1.01	(0.89–1.15)^b
SELECT	Klein et al., 2011 [100]	>50 yrs. men not at risk for prostate cancer, U.S., Canada and Puerto Rico	1108	8696	1132	8752	1.02	(0.92–1.14)^b
Prostate cancer
NPC	Clark et al., 1996 [102]	Patients with history of basal or squamous cell skin cancer	35	659	13	653	0.37	(0.18–0.71)
NPC	Duffield-Lillico et al., 2003 [95]	Patients with history of basal or squamous cell skin cancer	42	470	22	457	0.48	(0.28–0.80)
SELECT	Lippman et al., 2009 [99]	>50 yrs. men not at risk for prostate cancer, U.S., Canada and Puerto Rico	416	8696	432	8752	1.04	(0.87–1.24)^b
SELECT	Klein et al., 2011 [100]	>50 yrs. men not at risk for prostate cancer, U.S., Canada and Puerto Rico	529	8696	575	8752	1.09	(0.93–1.27)^b
SELECT	Klein et al., 2011 [100]	>50 yrs. men not at risk for prostate cancer, U.S., Canada and Puerto Rico High-grade disease (Gleason score ≥7)	133	8696	161	8752	1.21	(0.90–1.63)^b
	Marshall et al., 2011 [96]	Men at high risk for prostate cancer, U.S.	49	134	48	135	0.91^c	(0.55–1.52)^c
	Marshall et al., 2011 [96]	Men at high risk for prostate cancer, U.S. (only subjects for which plasma Se levels were available)	47	130	45	125	0.97	(0.68–1.39)
	Algotar et al., 2013 [97]	Men at high risk for prostate cancer, U.S. and New Zealand	26	232	24	234	0.94	(0.52–1.70)
	Algotar et al., 2013 (400 mcg/day Se) [97]	Men at high risk for prostate cancer, U.S. and New Zealand	26	232	23	233	0.90	(0.48–1.66)
Bladder cancer
NPC	Clark et al., 1996 [102]	Patients with history of basal or squamous cell skin cancer	6	659	8	653	1.32	(0.40–4.61)
NPC	Duffield-Lillico et al., 2002 [93]	Patients with history of basal or squamous cell skin cancer	8	629	10	621	1.28	(0.50–3.25)
SELECT	Lotan et al., 2012 [113]	>50 yrs. men not at risk for prostate cancer, U.S., Canada and Puerto Rico	53	8696	60	8752	1.13	(0.78–1.63)^b
Lung cancer
NPC	Clark et al., 1996 [102]	Patients with history of basal or squamous cell skin cancer	31	659	17	653	0.54	(0.30–0.98)
NPC	Duffield-Lillico et al., 2002 [93]	Patients with history of basal or squamous cell skin cancer	35	629	25	621	0.74	(0.44–1.24)
SELECT	Lippman et al., 2009 [99]	>50 yrs. men not at risk for prostate cancer, U.S., Canada and Puerto Rico	67	8696	75	8752	1.12	(0.73–1.72)^b
SELECT	Klein et al., 2011 [100]	>50 yrs. men not at risk for prostate cancer, U.S., Canada and Puerto Rico	92	8696	94	8752	1.02	(0.70–1.50)^b
Colorectal cancer
NPC	Clark et al., 1996 [102]	Patients with history of basal or squamous cell skin cancer	19	659	8	653	0.42	(0.18–0.95)
NPC	Duffield-Lillico et al., 2002 [93]	Patients with history of basal or squamous cell skin cancer	19	629	9	621	0.46	(0.21–1.02)
SELECT	Lippman et al., 2009 [99]	>50 yrs. men not at risk for prostate cancer, U.S., Canada and Puerto Rico	60	8696	63	8752	1.05	(0.66–1.67)^b
SELECT	Klein et al., 2011 [100]	>50 yrs. men not at risk for prostate cancer, U.S., Canada and Puerto Rico	75	8696	74	8752	0.96	(0.63–1.46)^b
Breast cancer
NPC	Clark et al., 1996 [102]	Patients with history of basal or squamous cell skin cancer	3	659	9	653	2.88	(0.72–16.5)
NPC	Duffield-Lillico et al., 2002 [93]	Patients with history of basal or squamous cell skin cancer	6	629	11	621	1.89	(0.69–5.14)
	Lubinski et al., 2011 [101] (250 μg/day inorganic Se)	Women with a BRCA1 mutation	45	-^d	60	-^d	1.4	(0.9–2.0)
Melanoma
NPC	Clark et al., 1996 [102]	Patients with history of basal or squamous cell skin cancer	8	659	8	653	0.97	(0.32–2.96)
NPC	Duffield-Lillico et al., 2002 [93]	Patients with history of basal or squamous cell skin cancer	9	629	11	621	1.18	(0.49–2.85)
Nonmelanoma skin cancer
NPC	Duffield-Lillico et al., 2003 [94]	Patients with history of basal or squamous cell skin cancer	not provided	629	not provided	621	1.17	(1.02–1.34)
	Dreno et al., 2007 [98]	Recent organ transplant patients	2	93	6	91	3.07	(0.5–31.1)
NPC	Reid et al., 2008 [123]	Patients with history of basal or squamous cell skin cancer	80	161	99	154	1.49	(1.10–2.03)
NPC	Reid et al., 2008 (400mcg/day Se) [123]	Patients with history of basal or squamous cell skin cancer	108	213	98	210	0.88	(0.66–1.16)
NM skin cancer—Squamous cell carcinoma
NPC	Clark et al., 1996 [102]	Patients with history of basal or squamous cell skin cancer	190	659	218	653	1.14	(0.93–1.39)
NPC	Duffield-Lillico et al., 2003 [94]	Patients with history of basal or squamous cell skin cancer	not provided	629	not provided	621	1.25	(1.03–1.51)
NPC	Reid et al., 2008 [123]	Patients with history of basal or squamous cell skin cancer	42	161	65	154	1.76	(1.18–2.66)
NPC	Reid et al., 2008 (400mcg/day Se) [123]	Patients with history of basal or squamous cell skin cancer	53	213	56	210	1.05	(0.71–1.56)
NM skin cancer—Basal cell carcinoma
NPC	Clark et al., 1996 [102]	Patients with history of basal or squamous cell skin cancer	350	659	377	653	1.10	(0.95–1.28)
NPC	Duffield-Lillico et al., 2003 [94]	Patients with history of basal or squamous cell skin cancer	not provided	629	not provided	621	1.09	(0.94–1.26)
NPC	Reid et al., 2008 [123]	Patients with history of basal or squamous cell skin cancer	69	161	75	154	1.20	(0.85–1.68)
NPC	Reid et al., 2008 (400mcg/day Se) [123]	Patients with history of basal or squamous cell skin cancer	83	213	76	210	0.90	(0.65–1.24)
^aRelative risk of cancer in in supplemented vs. nonsupplemented individuals.
^b99% confidence interval.
^cUnpublished data (courtesy of Dr. James Marshall).
^d1135 women with a BRCA1 mutation randomized to Se or placebo.

Figure 2 Relative risk (RR) for selected cancers in randomized, placebo-controlled trials (with 200 μg of organic Se when not otherwise specified; see Table 2 for references numbers).

Figure 3 Relative risk (RR) for selected cancers in a natural experiment investigated in Reggio Emilia, northern Italy, where residents consumed drinking water with high inorganic hexavalent Se content (around 8 μg/l) as only distinctive feature (Vinceti et al., 1995, 1998, and 2000 [119, 121, 130]).

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