Glyphosate epidemiology expert panel review: a weight of evidence systematic review of the relationship between glyphosate exposure and non-Hodgkin’s lymphoma or multiple myeloma

Figures & data

Table 1. Relevant studies for glyphosate review: non-Hodgkin’s lymphoma (NHL) and multiple myeloma (MM).

Author, year	Study location(s)	Study design	More recent analysis	Outcome
Cantor et al. 1992	Iowa + Minnesota	Case-control	De Roos et al. 2003	NHL
Nordstrom et al. 1998	Sweden	Case-control	Hardell et al. 2002	HCL
Hardell & Eriksson 1999	Sweden	Case-Control	Hardell et al. 2002	NHL excluding HCL
McDuffie et al. 2001	Canada	Case-control	n/a	NHL
Hardell et al. 2002	Sweden	Case-control (pooled)	n/a	NHL + HCL
De Roos et al. 2003	Nebraska	Case-control (pooled)	n/a	NHL
	Iowa/Minnesota
	Kansas
De Roos et al. 2005	Iowa, North Carolina	Cohort	n/a	NHL, MM
Eriksson et al. 2008	Sweden	Case-control	n/a	NHL
Orsi et al. 2009	France	Case-control	n/a	NHL, MM
Hohenadel et al. 2011	Canada	Case-control	Extension of McDuffie et al. 2001	NHL
Cocco et al. 2013	Czech Republic, France, Germany, Ireland, Italy, Spain	Case-control	n/a	B-cell lymphoma
Brown et al. 1993	Iowa	Case-control	n/a	MM
Landgren et al. 2009	Iowa	Prevalence	n/a	MGUS
	North Carolina	Case-control
	Minnesota
Pahwa et al. 2012	Canada	Case-control	Kachuri et al. 2013	MM
Kachuri et al. 2013	Canada	Case-control	n/a	MM
Sorahan 2015	Iowa, North Carolina	Cohort	Reanalysis of De Roos et al. 2005	MM

HCL: hairy cell leukemia; MGUS: monoclonal gammopathy of undetermined significance.

Table 2. Results for glyphosate: Non-Hodgkin’s lymphoma (NHL).

Author, year (study design)	# cases, controls total or exposed	OR/RR (95% CI)	Multivariate adjustments	Outcome
McDuffie et al. 2001	517, 1506 [total]			NHL
(case-control)	51, 133	Any use OR = 1.2 (95% CI 0.8, 1.7)	Age, province, medical conditions
	28, 97	≤2 days/year OR = 1.0 (95% CI 0.6, 1.6)	Age, province
	23, 36	>2 days/year OR = 2.1 (95% CI 1.3, 2.7)
Hardell et al. 2002	515, 1141 [total]			NHL + HCL
(case-control)	8, 8	Any use OR = 3.0 (95% CI 1.1, 8.5)	None
	8, 8	Any use OR = 1.9 (95% CI 0.6, 6.2)	Multivariate (unspecified)
De Roos et al. 2003	650, 1933 [total]			NHL
(case-control)	36, 61	Any use OR = 2.1 (95% CI 1.1, 4.0)	Age, other pesticides, study site
	36, 61	Any use OR = 1.6 (95% CI 0.9, 2.8)	Age, other pesticides, study site, priors for chemical class and probability of being carcinogenic [hierarchical model]
De Roos et al. 2005	71 exposed cases	Any use RR = 1.1 (95% CI 0.7, 1.9)	Age, education, smoking, alcohol, family history, state, 10 pesticides	NHL
(cohort, n = 57 311)	21 unexposed cases
	29 cases	1–20 days RR = 1.0 (referent)	same
	15 cases	21–56 days RR = 0.7 (95% CI 0.4, 1.4)
	17 cases	57–2678 days RR = 0.9 (95% CI 0.5, 1.6)
Eriksson et al. 2008	910, 1016 [total]			NHL
(case-control)	29, 18	Any use OR = 2.0 (95% CI 1.1, 3.7)	Age, sex, year of diagnosis or enrollment
	17, 9	>10 days OR = 2.4 (95% CI 1.0, 5.4)	Same
Orsi et al. 2009	244, 436 total			NHL
(case-control)	12, 24	Any use OR = 1.0 (95% CI 0.5, 2.2)	Age, center, socioeconomic category
Cocco et al. 2013	2348, 2462 [total]			B-cell lymphoma
(case-control)	4, 2	Any use OR = 3.1 (95% CI 0.6, 17.1)	Age, sex, education, study center

CI: confidence interval; HCL: hairy cell leukemia; OR: odds ratio; RR: relative risk.

Table 3. Results for glyphosate: multiple myeloma (MM).

Author, year	# cases, controls	OR/RR	Multivariate adjustments	Outcome
(study design)	Total or exposed	(95% CI)
Brown et al. 1993	173, 650 [total]
(case-control)	11, 40	Any use OR = 1.7 (95% CI 0.8, 3.6)	Age, vital status	MM
De Roos et al. 2005	24 exposed cases	Any use RR = 1.1 (95% CI 0.5, 2.4)	Age	MM
(cohort, n = 57 311)	Eight unexposed cases
	Not specified	Any use RR = 2.6 (95% CI 0.7, 9.4)	Age, education, smoking, alcohol, family history, state, 10 pesticides
	Eight exposed cases	1–20 days RR = 1.0 (referent)	Age, education, smoking, alcohol, family history, state, 10 pesticides
	Five exposed cases	21–56 days RR = 1.1 (95% CI 0.4, 3.5)
	Six exposed cases	57–2678 days RR = 1.9 (95% CI 0.6, 6.3)
Orsi et al. 2009	56, 313 [total]			MM
(case-control)	5, 18	Any use OR = 2.4 (95% CI 0.8, 7.3)	Age, center, socioeconomic category
Kachuri et al. 2013	342, 1357 [total]			MM
(case-control)	23, 108	Any use OR = 1.1 (95% CI 0.7, 1.9)	Age, province, smoking, selected medical conditions, family history of cancer
			Same
	11, 78	≤2 days/year OR = 0.7 (95% CI 0.4, 1.4)
	10, 26	>2 days/year OR = 2.1 (95% CI 0.95, 4.7)
Sorahan 2015	24 exposed cases	Any use RR = 1.1 (95% CI 0.5, 2.5)	Age	MM
	Eight unexposed cases
Reanalysis of  De Roos et al. 2005
	24 exposed cases	Any use RR = 1.2 (95% CI 0.5, 2.9)	Age, sex, education, smoking, alcohol, family history of cancer, education, 10 pesticides
	Eight unexposed cases
	Eight cases	Never used RR = 1.0 (referent)	Age, sex, education, smoking, alcohol, family history of cancer, education, 10 pesticides
	10 exposed cases	1–20 days RR = 1.1 (95% CI 0.4, 3.0)
	Eight exposed cases	21–57 days RR = 1.5 (95% CI 0.5, 4.3)
	Six exposed cases	57–2678 days RR = 1.4 (95% CI 0.4, 4.5)

CI: confidence interval; HCL: hairy cell leukemia; OR: odds ratio; RR: relative risk.

1. Reanalysis of De Roos et al. to assess the exclusion of 14 000 with some missing covariate data as the explanation for the difference in RRs adjusted for age (RR = 1.1) versus adjusted for age, education, smoking alcohol, family history, state and 10 pesticides (OR = 2.6).

Table 4. Validity considerations for glyphosate studies.

First author, year	Recall bias	Exposure misclassification	Exposure–response and trend test	Selection bias	Adjusted for confounding from other pesticides yes/no	Adjusted for confounding from other variables yes/no	Pathology review of cases	Proxies %cases/%controls	Bias from sparse data	Blinding of interviews	Consideration of latency
Brown et al. 1993	Likely	Moderate ever/never	No	Unlikely	No	Yes	Yes	42% for cases; 30% for controls	No	Unclear	No
McDuffie et al. 2001	Likely	Moderate ever/never; appreciable days of use	Yes, no trend test	Likely	No	Yes and no	Yes	21% cases; 15% controls	No	Unclear	No
Hardell et al. 2002	Likely	Moderate ever/never; appreciable in days of use analysis	No	Unlikely	Yes, but variables not specified	Unclear	Yes for NHL, unclear for HCL	43% NHL cases and controls, 0% for HCL	Possible	Yes	No
De Roos et al. 2003	Likely in original publications	Moderate ever/never	No	Likely, in original publications	Yes	Yes	Yes	31% for cases; 40% for controls	No	Yes	No
De Roos et al. 2005	No	Moderate ever/never; appreciable in days of use analysis	Yes, yes	Unlikely	Yes	Yes	Yes	No	Possible in some analyses	N/A	No
Eriksson et al. 2008	Likely	Moderate ever/never	Yes, no trend test	Unlikely	Yes	Age, sex, year of diagnosis	Yes	No	Possible in some analyses	Yes	Yes
Orsi et al. 2009	Likely	Moderate ever/never	No	Likely	No	Yes	Yes	No	Possible	Yes	No
Cocco et al. 2013	Likely	Likely	No	Likely	No	No	20%	No	Possible	Unclear	No
Kachuri et al. 2013	Likely	Moderate ever/never; appreciable in days of use analysis	Yes, no trend test	Likely	No	Yes	Yes	Excluded	No	Unclear	No

NHL: non-Hodgkin’s lymphoma.

Table 5. Results as presented by Brown et al. (1993) forglyphosate exposure.

	Case	Control	Total
Exposed	11	40	51
Unexposed	62	272	334
Total	73	312	385

OR_unadjusted = 1.2, 95% CI 0.5, 2.6.

Table 6. Results for glyphosate exposure using all the cases and controls from Brown et al. (1993).

	Case	Control	Total
Exposed	11	40	51
Unexposed	162	610	772
Total	173	650	823

OR_unadjusted = 1.0, 95% CI 0.5, 2.1.

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