Table 1.
Design characteristics of studies of glyphosate exposure and risk of lymphohematopoietic cancer (LHC), including non-Hodgkin lymphoma (NHL), NHL subtypes, Hodgkin lymphoma (HL), multiple myeloma (MM), and leukemia.
| Authors | Year | Outcomes studied | Study location | Study design | Study years | Source population | Subject identification | Subject participation | Subjects (n) | Proxy respondents | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Brown et al.[35] | 1990 | Leukemia (including myelodysplasias) | United States (Iowa and Minnesota) | Population-based case-control | 1980–1983 | White men aged ≥ 30 years in Iowa and Minnesota, excluding Minneapolis, St. Paul, Duluth, and Rochester | Cases: Iowa Tumor Registry and special surveillance of Minnesota hospital and pathology laboratory records Controls: random-digit dialing if aged < 65 years, Medicare files if aged ≥ 65 years, state death certificate files if deceased | Cases: 86% Controls: 77% random digit dialing, 79% Medicare, 77% proxies for deceased Supplemental interview: 93% cases, 96% controls | Cases: 578 Controls: 1,245 Supplemental interview: 86 cases, 203 controls | Cases: 238 (41%) Controls: 425 (34%) Supplemental interview, 63 (73%) cases, 57 (28%) controls | ||||||||||
| Brown et al.[32] | 1993 | MM | United States (Iowa) | Population-based case-control | 1981–1984 | White men aged ≥ 30 years in Iowa | Cases: Iowa Health Registry Controls: random-digit dialing if aged < 65 years, Medicare files if aged ≥ 65 years, state death certificates if deceased | Cases: 84% Controls: 78% overall | Cases: 173 Controls: 650 | Cases: 72 (42%) Controls: 198 (30%) | ||||||||||
| Cantor et al.[24] | 1992 | NHL | United States (Iowa and Minnesota) | Population-based case-control | 1980–1983 | White men aged ≥ 30 years in Iowa and Minnesota, excluding Minneapolis, St. Paul, Duluth, and Rochester | Cases: Iowa State Health Registry and special surveillance of Minnesota hospital and pathology laboratory records Controls: random-digit dialing if aged < 65 years, Medicare files if aged ≥ 65 years, state death certificate files if deceased | Cases: 89% Controls: 77% random-digit dialing, 79% Medicare, 77% proxies for deceased | Cases: 622 Controls: 1245 | Cases: 184 (30%) Controls: 425 (34%) | ||||||||||
| Cocco et al.[18] | 2013 | B-cell NHL | Europe (Czech Republic, France, Germany, Ireland, Italy, and Spain) | Population- and hospital-based case-control | 1998–2004 | Persons aged ≥ 17 years in Germany and Italy general populations, and in referral areas of participating hospitals in Czech Republic, France, Ireland, and Spain | Cases: NR Controls: random sampling of population registers in Germany and Italy; recruitment from hospital departments for infectious and parasitic (17.6%), mental and nervous (14.6%), circulatory (8.7%), digestive (7.1%), endocrine and metabolic (4.1%), respiratory (3.9%), and several other conditions (33.2%), excluding cancer, in Czech Republic, France, Ireland, and Spain | Cases: 88% overall; 90% Czech Republic, 91% France, 87% Germany, 90% Ireland, 93% Italy, 82% Spain Controls: 69% overall, 81% hospital-based, 52% population-based; 60% Czech Republic, 74% France, 44% Germany, 75% Ireland, 66% Italy, 96% Spain | Cases: 2348 Controls: 2462 | None | ||||||||||
| De Roos et al.[13] | 2003 | NHL | United States (Nebraska, Iowa, Minnesota, and Kansas) | Population-based case-control (pooled analysis of 3 studies) | 1979–1986 | White men aged ≥ 21 years in one of the 66 counties of eastern Nebraska; white men aged ≥ 30 years in Iowa and Minnesota, excluding Minneapolis, St. Paul, Duluth, and Rochester; white men aged ≥ 21 years in Kansas | Cases: Nebraska Lymphoma Study Group and area hospitals; Iowa State Health Registry; special surveillance of Minnesota hospital and pathology laboratory records; University of Kansas Cancer Data Service registry Controls: random-digit dialing if aged < 65 years, Medicare files if aged ≥ 65 years, state death certificate files if deceased | Cases: 91% Nebraska (93% living, 89% deceased); 89% Iowa and Minnesota; 96% Kansas Controls: 85% Nebraska; 77% random-digit dialing, 79% Medicare, 77% deceased (proxies) Iowa and Minnesota; 93% Kansas Analysis restricted to subjects who lived or worked on a farm before 18 years of age (% NR); analysis of multiple pesticides restricted to subjects with non-missing data (75% cases, 75% controls) | Cases: 650 (in analyses of multiple pesticides) Controls: 1933 (in analyses of multiple pesticides) | Cases: 201 (30.9%) (in analyses of multiple pesticides) Controls: 767 (39.7%) (in analyses of multiple pesticides) | ||||||||||
| De Roos et al.[12] | 2005 | LHC, NHL, MM, leukemia | United States (Iowa and North Carolina) | Prospective cohort | 1993–1997 through 2001 Median = 6.7 years | Private and commercial pesticide applicators in Iowa and North Carolina who were licensed to apply restricted-use pesticides | Pesticide applicators identified when seeking a state-issued restricted-use pesticide license; invited to complete the enrollment questionnaire at the licensing facility | 298 subjects (0.5%) lost to follow-up or with no person-time contributed > 80% of eligible pesticide applicators enrolled in study by completing on-site questionnaire 44% of applicators completed take-home questionnaire | Eligible cohort: 36,509–49,211 in analyses adjusted for demographics and lifestyle 30,613–40,719 in analyses additionally adjusted for other pesticides | None | ||||||||||
| Eriksson et al.[14] | 2008 | NHL, B-cell NHL, SLL/CLL, FL grades I-III, DLBCL, other specified B-cell NHL, unspecified B-cell NHL, T-cell NHL, unspecified NHL | Europe (Sweden) | Population-based case-control | 1999–2002 | Adults aged 18–74 years in 4 of 7 health service regions in Sweden associated with university hospitals in Lund, Linköping, Örebro, and Umeå | Cases: contact with treating physicians and pathologists Controls: national population registry | Cases: 81% Controls: 65% (92% of initially enrolled controls with 71% participation) | Cases: 995 Controls: 1016 | None | ||||||||||
| Hardell and Eriksson[27] | 1999 | NHL | Europe (Sweden) | Population-based case-control | 1987–1990 | Men aged ≥ 25 years in the four northernmost counties of Sweden and three counties in mid-Sweden | Cases: regional cancer registries Controls: national population registry if living, national registry for causes of death if deceased | Cases: 91% (91% living, 92% deceased) Controls: 84% (83% living, 85% deceased) | Cases: 404 Controls: 741 | Cases: 177 (44%) Controls: NR (∼44%; matched to cases) | ||||||||||
| Hardell et al.[15] | 2002 | NHL including hairy-cell leukemia | Europe (Sweden) | Population-based case-control | 1987–1990 | Men aged ≥ 25 years in the four northernmost counties of Sweden and three counties in mid-Sweden (for NHL) or in the entire country of Sweden (for hairy-cell leukemia) | Cases: regional cancer registries for NHL, national cancer registry for hairy-cell leukemia Controls: national population registry, national registry for causes of death if deceased | Cases: 91% Controls: 84% | Cases: 515 Controls: 1141 | Cases: ∼35% (NR) Controls: ∼29% (NR) | ||||||||||
| Hohenadel et al.[28] | 2011 | NHL | Canada (Alberta, British Columbia, Manitoba, Ontario, Quebec, and Saskatchewan) | Population-based case-control | 1991–1994 | Men aged ≥ 19 years in Alberta, British Columbia, Manitoba, Ontario, Quebec, and Saskatchewan | Cases: hospital records in Quebec, cancer registries in all other provinces Controls: provincial health insurance records in Alberta, Saskatchewan, Manitoba, and Quebec; computerized telephone listings in Ontario; voter lists in British Columbia | Cases: 67% Controls: 48% Based on postal codes, respondents were not more or less likely than non-respondents to live in a rural area. | Cases: 513 Controls: 1506 | Cases: 110 (21%) Controls: 220 (15%) | ||||||||||
| Kachuri et al.[33] | 2013 | MM | Canada (Alberta, British Columbia, Manitoba, Ontario, Quebec, and Saskatchewan) | Population-based case-control | 1991–1994 | Men aged ≥ 19 years (≥ 30 years in analysis) in Alberta, British Columbia, Manitoba, Ontario, Quebec, and Saskatchewan | Cases: hospital records in Quebec, cancer registries in all other provinces Controls: provincial health insurance records in Alberta, Saskatchewan, Manitoba, and Quebec; computerized telephone listings in Ontario; voter lists in British Columbia | Cases: 58% Controls: 48% Based on postal codes, respondents were not more or less likely than non-respondents to live in a rural area. | Cases: 342 Controls: 1357 | Cases: 103 (30%) Controls: 202 (15%) | ||||||||||
| Karunanayake et al.[31] | 2012 | HL | Canada (Alberta, British Columbia, Manitoba, Ontario, Quebec, and Saskatchewan) | Population-based case-control | 1991–1994 | Men aged ≥ 19 years in Alberta, British Columbia, Manitoba, Ontario, Quebec, and Saskatchewan | Cases: hospital records in Quebec, cancer registries in all other provinces Controls: provincial health insurance records in Alberta, Saskatchewan, Manitoba, and Quebec; computerized telephone listings in Ontario; voter lists in British Columbia | Cases: 68% Controls: 48% Based on postal codes, respondents were not more or less likely than non-respondents to live in a rural area. | Cases: 316 Controls: 1506 | Cases: NR Controls: 220 (15%) | ||||||||||
| Kaufman et al.[36] | 2009 | Leukemia | Bangkok, Thailand | Hospital-based case-control | 1997–2003 | Patients aged ≥ 18 years residing in Bangkok proper and suburbs of Nonthaburi, Nakornpathom, Patumthani, Samutprakarn, and Samusakorn, admitted to Siriraj Hospital or Dhonburi Hospital | Cases: hospital records Controls: hospital records for acute infection or inflammation (33%), trauma (22%), acute abdominal emergencies such as appendicitis (27%), or various other diagnoses with elective admission, such as cataract, hernia repair, or cosmetic surgery (17%), excluding head trauma with loss of consciousness or cancer; controls at Dhonburi Hospital (a nearby private hospital) matched to 21 cases admitted to private wards for wealthy patients | Cases: 100% Controls: 100% | Cases: 180 Controls: 756 | None | ||||||||||
| Lee et al.[29] | 2004 | NHL | United States (Nebraska, Iowa, and Minnesota) | Population-based case-control (pooled analysis of 2 studies) | 1980–1986 | White men and women aged ≥ 21 years in one of 45 counties in eastern Nebraska; white men aged ≥ 30 years in Iowa and Minnesota, excluding Minneapolis, St. Paul, Duluth, and Rochester | Cases: Nebraska Lymphoma Study Group and area hospitals; Iowa State Health Registry; special surveillance of Minnesota hospital and pathology laboratory records Controls: random-digit dialing if aged < 65 years, Medicare files if aged ≥ 65 years, state death certificate files if deceased | Cases: 91% Nebraska, 89% Iowa and Minnesota Controls: 85% Nebraska, 78% Iowa and Minnesota | Cases: 872 Controls: 2336 | Cases: 266 (31%) Controls: 779 (33%) | ||||||||||
| McDuffie et al.[16] | 2001 | NHL | Canada (Alberta, British Columbia, Manitoba, Ontario, Quebec, and Saskatchewan) | Population-based case-control | 1991–1994 | Men aged ≥ 19 years in Alberta, British Columbia, Manitoba, Ontario, Quebec, and Saskatchewan | Cases: hospital records in Quebec, cancer registries in all other provinces Controls: provincial health insurance records in Alberta, Saskatchewan, Manitoba, and Quebec; computerized telephone listings in Ontario; voter lists in British Columbia | Cases: 67% Controls: 48% Based on postal codes, respondents were not more or less likely than non-respondents to live in a rural area. | Cases: 517 Controls: 1506 | Cases: ∼21% (NR) Controls: 220 (15%) | ||||||||||
| Nordström et al.[30] | 1998 | Hairy-cell leukemia | Europe (Sweden) | Population-based case-control | 1987–1992 (1993 for one case) | Men living in Sweden | Cases: national cancer registry Controls: national population registry | Cases: 91% Controls: 83% | Cases: 111 Controls: 400 | Cases: 4 (4%) Controls: 5 (1%) | ||||||||||
| Orsi et al.[17] | 2009 | LHC, NHL, DLBCL, FL, LPS, CLL, hairy-cell leukemia, HL, MM | Europe (France) | Hospital-based case-control | 2000–2004 | Men aged 20–75 years living in the catchment areas of the main hospitals in Brest, Caen, Nantes, Lille, Toulouse, and Bordeaux, with no history of immunosuppression or taking immunosuppressant drugs | Cases: hospital records Controls: hospital records for orthopedic or rheumatological conditions (89.3%), gastrointestinal or genitourinary tract diseases (4.8%), cardiovascular diseases (1.1%), skin and subcutaneous tissue disease (1.8%), and infections (3.0%), excluding patients admitted for cancer or a disease directly related to occupation, smoking, or alcohol abuse | Cases: 95.7% Controls: 91.2% | Cases: 491 LHC, 244 NHL, 104 LPS, 87 HL, 56 MM Controls: 456 | None | ||||||||||
| Pahwa et al.[34] | 2012 | MM | Canada (Alberta, British Columbia, Manitoba, Ontario, Quebec, and Saskatchewan) | Population-based case-control | 1991–1994 | Men aged ≥ 19 years in Alberta, British Columbia, Manitoba, Ontario, Quebec, and Saskatchewan | Cases: hospital records in Quebec, cancer registries in all other provinces Controls: provincial health insurance records in Alberta, Saskatchewan, Manitoba, and Quebec; computerized telephone listings in Ontario; voter lists in British Columbia | Cases: 58% Controls: 48% Based on postal codes, respondents were not more or less likely than non-respondents to live in a rural area. | Cases: 342 Controls: 1506 | Cases: 103 (30%) Controls: 220 (15%) | ||||||||||
| Sorahan[26] | 2015 | MM | United States (Iowa and North Carolina) | Prospective cohort | 1993–1997 through 2001 Median = 6.7 years | Private and commercial pesticide applicators in Iowa and North Carolina who were licensed to apply restricted-use pesticides | Pesticide applicators identified when seeking a state-issued restricted-use pesticide license; invited to complete the enrollment questionnaire at the licensing facility | 298 subjects (0.5%) lost to follow-up or with no person-time contributed > 80% of eligible pesticide applicators enrolled in study by completing on-site questionnaire 44% of applicators completed take-home questionnaire | Eligible cohort (1): 54,315 excluding subjects with cancer before enrollment, loss to follow-up, missing age at enrollment, or missing glyphosate use 49,211 also excluding missing education, smoking, or alcohol 40,719 excluding missing other pesticides Eligible cohort (2): 53,656 excluding subjects with cancer before enrollment, loss to follow-up, missing age at enrollment, missing glyphosate use, or missing cumulative exposure days of glyphosateuse 53,304 also excluding missing intensity of glyphosate use Eligible cohort (3): 55,934 excluding subjects with cancer before enrollment, loss to follow-up, or missing age at enrollment | None | ||||||||||