Pesticides, soft-tissue sarcoma and non-Hodgkin lymphoma – historical aspects on the precautionary principle in cancer prevention

Figures & data

Table I.  Clinical observation of seven male cases with soft-tissue sarcoma and exposure to phenoxyacetic acids [6].

Age	Occupation	Diagnosis	Exposure history	Latency
62 years	Forestry worker	Leiomyosarcoma	1963–1976, 2,4,5-T during 14 weeks	13 years
57 years	Forestry worker	Mesenchymal tumour, probably liposarcoma	1950's–1960's, 2,4,D and 2,4,5-T during 21 weeks	>17 years
49 years	Owner of workshop	Mesenchymal tumour, probably neurofibrosarcoma	1961–1972, stored and handled phenoxy herbicides during 11 months per year	15 years
60 years	Forestry worker	Leiomyosarcoma	1961–1966, phenoxy herbicides during 20 weeks	10 years
44 years	Agriculture, forestry	Rhabdomyosarcoma	1960–1968, phenoxy herbicides during 16 weeks	14 years
76 years	Farmer	Myxofibrosarcoma	1950's, phenoxy herbicides	>13 years
67 years	Forestry worker	Polymorphcellular sarcoma, possibly rhabdomyosarcoma	1956–early 1960's, phenoxy herbicides	14 years

Table II.  Mantel-Haenszel odds ratio (OR) and 95% confidence interval (CI) for soft-tissue sarcoma and exposure to phenoxyacetic acids or chlorophenols. Stratification was made by age, vital status and study. Median number of days for controls was used as cut-off in dose-response calculations. Meta-analysis of four case-control studies on soft-tissue sarcoma including 434 cases and 948 controls [7–10].

Agent	Number of exposed cases/controls	OR	CI
Phenoxyacetic acids	59/59	2.7	1.9–4.7
1–24 days	19/30	1.7	0.9–3.5
> 24 days	40/29	3.7	2.4–7.8
2,4,5-T and combination	46/41	3.5	2.3–6.7
2,4-D only	5/9	1.4	0.4–5.1
MCPA only	8/9	1.6	0.6–5.3
Chlorophenols	34/34	3.3	1.8–6.1
1–77 days	22/15	3.0	1.1–7.3
> 77 days	22/19	3.4	1.7–7.8

Table III.  Mantel-Haenszel odds ratio (OR) and 90% confidence interval (CI) for exposure to dioxins in four case-control studies on soft-tissue sarcoma including 434 cases and 948 controls [7–10], [12]. Stratification was made according to study.

	Exposure <1 year			Exposure ≥1 years
Substance	Number of exposed cases/controls	OR	CI	Number of exposed cases/controls	OR	CI
All dioxins	58/74	2.4	1.7–3.4	24/9	6.4	3.5–12
TCDD	40/39	3.0	2.0–4.5	6/2	7.2	2.6–20
Other dioxins	18/35	1.7	0.98–2.9	18/7	6.2	2.9–13

Table IV.  Odds ratio (OR) and 95% confidence interval (CI) for non-Hodgkin lymphoma and exposure to different agents. Mantel-Haenszel method stratified by age was used in the first study [16], conditional logistic regression analysis in the second study [17], and unconditional logistic regression analysis with adjustment for age, sex and year of diagnosis (cases) or enrolment (controls) in the third study [unpublished data]. The analysis in study I was based on 105 cases and 335 controls [16], in study II on 404 cases and 741 controls [17], and in study III on 910 cases and 1016 controls [unpublished data]. Numbers of exposed cases and controls are given (Ca/Co).

	Study I [16]			Study II [17]			Study III [unpublished]
Agent	Ca/Co	OR	CI	Ca/Co	OR	CI	Ca/Co	OR	CI
Phenoxyacetic acids	25/24	5.5	2.7–11	51/71	1.5	0.9–2.4	47/26	2.0	1.2–3.4
2,4,5-T and combination	18/23	4.1	1.9–8.6	43/62	1.3	0.7–2.3	29/18	1.6	0.9–3.0
MCPA	4/0	–	–	12/11	2.7	1.0–7.0	21/9	2.8	1.3–6.2
Chlorophenols	35/35	4.8	2.7–8.8	57/92	1.1	0.7–1.8	40/36	1.2	0.8–2.0
Organic solvents	45/88	2.4	1.4–3.9	199/349	1.1	0.8–1.4	299/271	1.4	1.1–1.7

Table V.  Odds ratio (OR) and 95% confidence interval (CI) for different organohalogen compounds and NHL in relation to titre to Epstein-Barr virus early antigen (EA) IgG [26]. As cut-off the median concentration of the chemicals and titre to EA in the controls was used. Numbers (expressed in ng/g lipid) are shown for cases and controls. Adjustment was made for age, sex and body mass index. For abbreviations of chemicals, see text.

	EA ≤40			EA >40
Exposure	Cases/controls	OR	CI	Cases/controls	OR	CI
Sum of PCBs
≤ median 646	14/25	(1.0)	–	24/24	2.5	0.97–6.4
> median 646	20/29	2.1	0.7–6.1	39/20	5.2	1.9–14
HCB
≤ median 24	9/24	(1.0)	–	34/26	3.9	1.5–10
> median 24	25/30	2.5	0.9–6.7	31/19	5.3	1.9–15
p,p′-DDE
≤ median 271	20/28	(1.0)	–	26/22	1.8	0.8–4.1
> median 271	14/26	1.0	0.4–2.7	39/23	3.3	1.4–7.7
Sum of chlordanes
≤ median 19	13/23	(1.0)	–	24/27	1.8	0.7–4.7
> median 19	21/31	1.8	0.6–5.1	41/18	6.8	2.3–20
PBDE
≤ median 1.8	17/24	(1.0)	–	43/26	2.7	1.2–6.2
> median 1.8	17/30	0.9	0.4–2.3	22/19	1.8	0.7–4.5

Hardell L. Soft-tissue sarcomas and exposure to phenoxy acids: A clinical observation. Läkartidningen 1977; 74: 2753–4

 PubMedGoogle Scholar

Hardell L, Eriksson M, Axelson O, Fredriksson M. Dioxin and mortality from cancer. N Engl J Med 1991; 324: 1810–1

 Google Scholar

Hardell L, Eriksson M, Degerman A. Exposure to phenoxyacetic acids, chlorophenols, or organic solvents in relation to histopathology, stage, and anatomical localization of non-Hodgkin's lymphoma. Cancer Res 1994; 54: 2386–9

 PubMed Web of Science ®Google Scholar

Hardell L, Eriksson M. A case-control study of non-Hodgkin lymphoma and exposure to pesiticides. Cancer 1999; 85: 1353–60

 PubMed Web of Science ®Google Scholar

Hardell L, Björnfoth H, Hardell K, van Bavel B, Lindström G, Carlberg M, et al. Concentrations of organohalogen compounds and titers of antibodies to Epstein-Barr virus antigens and the risk for non-Hodgkin lymphoma. Organohalogen Compounds 2006; 68: 2535–8

 Google Scholar