TCDD and cancer: A critical review of epidemiologic studies

Figures & data

Figure 1.  Measured and estimated blood dioxin level (ppt) in selected studies. * 2,000 ppt. In square brackets, type of population (M, pesticide manufacturers; V, Vietnam Veterans; Sp, pesticide sprayers; S, Seveso) and average years between measured and estimated level.

Table 1.  Comparison of results of the first and the second follow-up of US pesticide manufacturing workers (modified from Cole et al., 2003).

Publication	Follow-up	All cancers		Lung cancer		NHL		STS
		O/E	SMR	O/E	SMR	O/E	SMR	O/E	SMR
Fingerhut et al., 1991	1942–1987	265/229.9	1.15	89/80.1	1.11	10/7.3	1.37	4/1.2	3.38
Steenland et al., 1999	1942–1993	377/333.6	1.13	125/117.9	1.06	12/10.9	1.10	4/1.7	2.32
Difference		112/103.7	1.08	36/37.8	0.95	2/3.6	0.56	0/0.5	0

Note. O = observed deaths; E = expected deaths; SMR = standardized mortality ratio; NHL = non-Hodgkin lymphoma; STS = soft-tissue sarcoma.

Figures in italics were derived from raw data reported in the papers.

Figure 2.  Relative risk of all-cancer mortality in the US cohort, by categories of cumulative dioxin exposure.

Figure 3.  Relative risk of all-cancer mortality in the US cohort, by categories of cumulative dioxin serum level, lagged 15 years.

Table 2.  Comparison of results of the first and the second publication of pesticide manufacturing workers from the Netherlands (factory A).

Publication	Follow-up	N workers	All cancers		Lung cancer		NHL
		E/U	E/U	RR	E/U	RR	E/U	RR
Hooiveld et al., 1998	1955–1991	549/482	51/7	4.1	14/1	6.5	3/1	1.7
Boers et al., 2010	1955–2006	539/482	81/31	1.31	20/7	1.15	4/3	0.92

Note. E = exposed; U = unexposed; N = number of cases; RR = relative risk; NHL = non-Hodgkin lymphoma.

Table 3.  Comparison of results of the first and the second follow-up of pesticide manufacturing workers from New Zealand.

Publication	Follow-up	N workers	All cancers		Lung cancer		NHL
			O/E	SMR	O/E	SMR	O/E	SMR
Kogevinas et al., 1992	1969–1987	782	15/11.99	1.25	2/3.56	0.56	0/0.32	0
‘t Mannetje et al., 2005	1969–2000	813	43/34.6	1.24	12/8.8	1.37	1/1.1	0.87
Difference			28/22.6	1.24	10/5.2	1.92	1/0.8	1.25
McBride et al., 2009	1969–2004	1134	196/196	1.0	61/55.5	1.1	3/1.9	1.6
Difference			184/184	1.0	59/51.9	1.1	3/1.6	1.9

Note. O = observed deaths; E = expected deaths; SMR = standardized mortality ratio; NHL = non-Hodgkin lymphoma.

Figures in italics were derived from raw data reported in the papers.

Table 4.  Comparison of results of the last and next-to-last follow-up of residents in Seveso—Cancer mortality.

Publication	Follow-up	All cancers		Lung cancer		NHL
		O/E	SMR	O/E	SMR	O/E	SMR
Zone A
Bertazzi et al., 1996	1976–1991	16/23.3	0.69	4/4.5	0.89	0/0.2	0
Consonni et al., 2008	1976–2001	42/40.8	1.03	11/8.7	1.26	3/0.9	3.35
Difference		26/17.4	1.49	7/4.2	1.65	3/0.7	4.44
Zone B
Bertazzi et al., 1996	1976–1991	152/147.9	1.03	36/31.7	1.14	2/2.5	0.79
Consonni et al., 2008	1976–2001	244/265.2	0.92	62/55.9	1.11	7/5.7	1.23
Difference		92/117.3	0.78	26/24.2	1.07	5/3.2	1.58
Zone R
Bertazzi et al., 1996	1976–1991	1008/1120.0	0.90	205/224.6	0.91	18/18.0	1.00
Consonni et al., 2008	1976–2001	1848/1905.2	0.97	383/390.8	0.98	40/40.4	0.99
Difference		840/785.2	1.07	178/166.3	1.07	22/22.4	0.98

Note. O = observed deaths; E = expected deaths; SMR = standardized mortality ratio; NHL = non-Hodgkin lymphoma.

Figures in italics were derived from raw data reported in the papers.

Table 5.  Comparison of results of the last and next-to-last follow-up of residents in Seveso—Cancer incidence.

Publication	Follow-up	All cancers		Lung cancer		NHL
		O/E	SIR	O/E	SIR	O/E	SIR
Zone A
Bertazzi et al., 1993	1977–1986	14/17.0	0.82	2/2.7	0.74	0/0.4	0
Pesatori et al., 2009	1977–1996	44/42.7	1.03	7/6.3	1.12	1/1.3	0.80
Difference		30/25.7	1.17	5/3.5	1.41	1/0.9	1.18
Zone B
Bertazzi et al., 1993	1977–1986	112/114.1	0.98	18/17.8	1.01	4/2.4	1.65
Pesatori et al., 2009	1977–1996	270/270.0	1.00	37/38.5	0.96	12/7.9	1.51
Difference		158/155.9	1.01	19/20.8	0.91	8/5.5	1.47
Zone R
Bertazzi et al., 1993	1977–1986	765/850.0	0.90	112/130.7	0.86	22/17.6	1.25
Pesatori et al., 2009	1977–1996	1808/1883.3	0.96	280/269.2	1.04	49/54.4	0.90
Difference		1043/1033.3	1.01	168/138.6	1.21	27/36.9	0.73

Note. O = observed cases; E = expected cases; SIR = standardized incidence ratio; NHL = non-Hodgkin lymphoma.

Figures in italics were derived from raw data reported in the paper.

Table 6.  Comparison of results of last and next-to-last follow-up of Ranch Hand veterans—Cancer mortality.

	N	Follow-up	All cancers		Lung cancer		NHL
			O/E	SMR	O/E	SMR	O/E	SMR
Ketchum et al., 1996	1261	1966–1993	30/33.3	0.90	12/13.0	0.92	1/0.7	1.43
Akhtar et al., 2004	1061*	1966–2000	45/61.7	0.73	21/24.1**	0.87	6/6.3***	0.95

Note. O = observed deaths; E = expected deaths; SMR = standardized mortality ratio; NHL = non-Hodgkin lymphoma.

*Whites only; **respiratory cancer; ***lymphohematopoietic neoplasms.

Table 7.  Relative risk of multiple myeloma mortality in selected studies of populations exposed to dioxin—Results reported before and after the 1997 IARC Monograph (IARC, 1997).

Population	Publication before the 1997 IARC Monograph				Publication after the 1997 IARC Monograph
	Reference	O	SMR	95% CI	Reference	O	SMR	95% CI
US pesticide mft	Fingerhut et al., 1991	5	1.6	0.5, 3.9	Steenland et al., 1999	10	2.07	0.99, 3.80
NZ pesticide mft	Kogevinas et al., 1992	1	6.25	0.16, 34.8	‘t Mannetje et al., 2005	3	5.51	1.14, 16.1
					McBride et al., 2009**	2	2.2	0.2, 8.1
Seveso, Zone A	Bertazzi et al., 1996*	0	0	0, 18.4	Consonni et al., 2008***	2	4.34	1.07, 17.5
Seveso, Zone B	Bertazzi et al., 1996*	5	3.3	1.1, 7.7	Consonni et al., 2008***	5	1.68	0.69, 4.10

Note. O = observed deaths; mft = manufacturers; SMR = standardized mortality ratio; CI = confidence interval.

*Similar results in the cancer incidence analysis (Bertazzi et al., 1993).

**Unclear why the expanded and updated cohort (McBride et al., 2009) has one less case of the earlier cohort (‘t Mannetje et al., 2005).

***Similar results in the cancer incidence analysis (Pesatori et al., 2009).

Figures in italics were derived from raw data reported in the paper.

Table 8.  Risk of female breast cancer among residents in Seveso.

	Incidence*			Mortality**
	O	SIR	95% CI	O	SMR	95% CI
Zone A	8	1.43	0.71, 2.87	2	0.60	0.15, 2.41
Zone B	30	0.85	0.59, 1.22	13	0.65	0.37, 1.12
Zone R	249	1.00	0.88, 1.15	133	0.87	0.73, 1.05

Note. O = observed cases/deaths; SIR, standardized incidence ratio; SMR = standardized mortality ratio; CI = confidence interval.

*Follow-up 1977–1996 (Pesatori et al., 2009).

**Follow-up 1976–2001 (Consonni et al., 2008).

Cole P, et al. (2003). Dioxin and cancer: A critical review. Regul Toxicol Pharmacol 38:378–388.

 PubMed Web of Science ®Google Scholar

Fingerhut MA, et al. (1991). Cancer mortality in workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin [see comments]. N Engl J Med 324:212–218.

 PubMed Web of Science ®Google Scholar

Steenland K, et al. (1999). Cancer, heart disease, and diabetes in workers exposed to 2,3,7,8- tetrachlorodibenzo-p-dioxin [see comments]. J Natl Cancer Inst 91:779–786.

 PubMed Web of Science ®Google Scholar

Hooiveld M, et al. (1998). Second follow-up of a Dutch cohort occupationally exposed to phenoxy herbicides, chlorophenols, and contaminants. Am J Epidemiol 147:891–901.

 PubMed Web of Science ®Google Scholar

Boers D, et al. (2010). Cause-specific mortality of Dutch chlorophenoxy herbicide manufacturing workers. Occup Environ Med 67:24–31.

 PubMed Web of Science ®Google Scholar

Kogevinas M, et al. (1992). Cancer Mortality in an International Cohort of Workers Exposed to Chlorophenoxy Herbicides, Chlorophenols and Contaminants. IARC Internal Report 92/002. Lyon, International Agency for Research on Cancer, 1992.

 Google Scholar

‘t Mannetje A, et al. (2005). Mortality in New Zealand workers exposed to phenoxy herbicides and dioxins. Occup Environ Med 62:34–40.

 PubMed Web of Science ®Google Scholar

McBride DI, et al. (2009). Mortality in workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin at a trichlorophenol plant in New Zealand. J Occup Environ Med 51:1049–1056.

 PubMedGoogle Scholar

Bertazzi P, Pesatori AC, Landi MT. (1996). Cancer mortality, 1976–1991, in the population exposed to 2,3,7,8-tetrachlrodibenzo-p-dioxin. Organohalogen Compounds 30:294–295.

 Google Scholar

Consonni D, et al. (2008). Mortality in a population exposed to dioxin after the Seveso, Italy, accident in 1976: 25 years of follow-up. Am J Epidemiol 167:847–858.

 PubMed Web of Science ®Google Scholar

Bertazzi A, et al. (1993). Cancer incidence in a population accidentally exposed to 2,3,7,8- tetrachlorodibenzo-para-dioxin [see comments]. Epidemiology 4:398–406.

 PubMed Web of Science ®Google Scholar

Pesatori AC, et al. (2009). Cancer incidence in the population exposed to dioxin after the “Seveso accident”: Twenty years of follow-up. Environ Health 8:39.

 PubMed Web of Science ®Google Scholar

Ketchum NS. (1996). The Air Force Health Study: An Epidemiologic Investigation of Health Effects in Air Force Personnel Following Exposure to Herbicides, Mortality Update to 1996. Interim Tech Report AL/AO-TR-1996-0068. Armstrong Laboratory, Brooks Air Force Base, TX.

 Google Scholar

Akhtar FZ, et al. (2004). Cancer in US Air Force veterans of the Vietnam War. J Occup Environ Med 46:123–136.

 PubMed Web of Science ®Google Scholar

International Agency for Research on Cancer (IARC). (1997). Polychlorinated dibenzo-para-dioxins IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Vol. 69. Polychlorinated Dibenzo-para-dioxins and Polychlorinated Dibenzofurans. Lyon: IARC, 33–343.

 Google Scholar