Gulf War and Health Volume 2: Insecticides and Solvents (2003) / Chapter Skim
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5. Cancer and Exposure to Insecticides
5. Cancer and Exposure to Insecticides
Pages 98-155
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From page 98... ...
A general introduction to cancer and to cancer epidemiology that applies to both the insecticide and solvent literature is provided here. Furthermore, for each cancer type reviewed by the committee, an overview of the cancer, its risk factors, and 5-year survival rates, as identified by the National Cancer Institute (NCT)
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From page 99... ...
For example, workers exposed to high concentrations of ionizing radiation, some chemicals, metals, and other substances have been shown to be at increased risk for cancer (ACS, 2002a)
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From page 100... ...
TARC also found 2 It is important to note the differences in the objective of the IARC program and the charge of this committee. The objective of the IARC program is to determine whether agents or occupational exposures are carcinogenic, whereas this committee is charged with determining whether or not there is an association between exposure to a specific agent or agents and a specific health outcome, such as a particular cancer.
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From page 101... ...
In addition to sex and smoking, other risk factors include alcohol consumption, vitamin A deficiency, exposure to ultraviolet radiation (sunlight) , increasing age, a weakened immune system, and occupational exposure to glues ~ ~ ~ _ _1~ _ J-1~ _ ~ __ _1~ _~ ~ I_ ~ 11 _ ~ ~ ~ 1 _ 1 ~ · 1 / , · 1 ~ ~7 tutu Susie order suos~an`;~s mung In Industry as petroleum, plastics, wood, textile, and leather working (ACS, 2000a, 2002b,c; NCI, 2002a,b)
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From page 102... ...
Cancers of the colon and rectum, sometimes referred to together as colorectal cancer, are the third most common cancers in the United States, excluding skin cancers. The 5-year relative survival rate is 61% (ACS, 2002a)
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From page 103... ...
Results of the studies considered for evidence of association are presented in Table 5.1. Stomach Cancer No studies meeting the committee's criteria for critical studies were available that evaluated the risk of stomach cancer associated with exposure to the specific insecticides or classes of insecticides used in the Gulf War.
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From page 104... ...
for those exposed to high concentrations of organophosphorous agents for at least 1 0 years, 10 years before diagnosis. However, all the findings related to pancreatic cancer and exposure to organophosphorous insecticides are weak, only a small number of cases were exposed, and the study is limited by the potential for selection bias due to the inclusion of controls with chronic (n = 93)
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From page 105... ...
The committee concludes, from its assessment of the epidemiologic literature, that there is inadequate/insuff~cient evidence to determine whether an association exists between chronic exposure to the insecticides under review and pancreatic cancer. TABLE 5.1 Selected Epidemiologic Studies—Pancreatic Cancer and Exposure to Insecticides Reference Study Population Exposed Estimated Cases Relative Risk (95% CI)
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From page 106... ...
The key studies reviewed by the committee are discussed below and results are in Table 5.2. No studies involving specific insecticides were considered critical for review by the committee.
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From page 107... ...
The committee concludes, from its assessment of the epidemiologic literature, that there is inadequate/insufficient evidence to tielermine whether an association exists between chronic exposure to the insecticides under review and hepatobiliary cancers. TABLE 5.2 Selected Epidemiologic Studies Hepatobiliary Cancers and Exposure to Insecticides Reference Study Population Exposed Estimated Relative Cases Risk (95% CI)
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From page 108... ...
. Epidemiologic Studies of Exposure to Insecticides As with several of the other cancer sites, very few studies examine the risk of lung cancer in relation to specific insecticides.
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From page 109... ...
The lack of exposure specificity limits the findings of these studies in determining an association between exposure to insecticides used in the Gulf War and lung cancer risk. Summary and Conclusion A number of epidemiologic studies have examined the relationship between lung cancer and exposure to the broad group of pesticides, but few examine the association with specific insecticides.
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From page 110... ...
. The 5-year survival rate can be as high as 80%, but the prognosis for people with primary bone cancer varies greatly, depending on the specific type of cancer and the stage at which it is diagnosed (ACS, 2000e; NCI, 2002i)
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From page 111... ...
and people with family histories of Gardner's syndrome (colonic polyps) or retinoblastoma are at increased risk for STS.
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From page 112... ...
v TABLE 5.4 Selected Epidemiologic Studies- Soft Tissue Sarcomas and Exposure to Insecticides Reference Study Population Class of Insecticides and Insecticides Case-Control Study Zahm et al., 1988 Residents of Kansas OrgaIlophosphorous agents Animal insecticides Crop insecticides Insecticides SON CANCER Exposed Estimated Relative Cases Risk (95% CI)
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From page 113... ...
(ACS, 2001 d; NCI, 20021~. Epidemiologic Studies of Exposure to Insecticides No epidemiologic studies were identified in the committee's literature review on the relationship between exposure to specific insecticides and skin cancer, and only one study on insecticides in general was identified.
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From page 114... ...
Breast cancer (ICD-9 174.0-174.9 for females) is the most common form of cancer among women and the second most common cause of death from cancer in women, exceeded only by lung cancer (ACS, 2001e)
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. Epidemiologic Studies of Exposure to Insecticides A number of epidemiologic studies have investigated breast cancer risk and exposure to pesticides, with particular attention to the role of specific organochIorine pesticides, including dichiorodipheny~trichIoroethane (DDT)
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From page 116... ...
The committee concludes, from its assessment of the epidemiologic literature, that there is inadequate/insufficient evidence to determine whether an association exists between chronic exposure to lindane or its isomers and breast cancer. TABLE 5.6 Selected Epidemiologic Studies Breast Cancer and Exposure to Insecticides Reference Study Population Exposed Estimated Relative Cases Risk (95% CI)
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From page 117... ...
. Occupational exposure to carcinogens such as benzidine and beta-naphthylamine, as seen among dye and rubber industry workers—has also been associated with significantly increased risks of bladder cancer (Miyakawa et al., 20011.
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From page 118... ...
. Epidemiologic Studies of Exposure to Insecticides A number of studies have examined the increased risk of urologic cancersincluding bladder, kidney, prostate, and testicular cancer among farmers and agricultural workers, but very few have examined the risk in relation to specific insecticides or to insecticides in general.
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From page 119... ...
An increased risk of kidney cancer- adjusted for age, body mass index, and smoking was observed among men who reported exposure to insecticides or herbicides for less than 20 years (OR = I.3, 95°/0 CT = 0.4 4.~) and for 20 years or more (OR = 3.9, 95°/0 C]
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From page 120... ...
The committee concludes, from its assessment of the epidemiologic literature, that there is inadequate/insufficient evidence to determine whether an association exists between chronic exposure to the insecticides under review and prostate, testicular, bladder, and kidney cancers. TABLE 5.7 Selected Epidemiologic Studies Urologic Cancers and Exposure to Insecticides Reference Study Population Exposed Estimated Relative Risk Cases (95% CI)
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From page 121... ...
As a result, studies often analyze the broader category of "brain or CNS cancers." Epidemiologic studies of brain and other CNS cancers must also address and consider the relatively low survival rate that limits the number of cases to interview and the aggressive nature of the disease, which adversely affects memory and the recall ability of patients. The key studies reviewed by the committee are discussed below, and relevant results are included in Table 5.~.
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From page 122... ...
Issues of exposure misclassification, potential recall bias, and lack of control for confounding variables limit the value of these studies for drawing a conclusion. Studies on pesticide applicators and farmers licensed to use pesticides also found an increased risk of brain and other CNS cancers but used job titles as surrogates of exposure to pesticides (Alberghini et al., ~ 99 I; Corrao et al., ~ 989; Figa-Talamanca et al., 1993b; Godon et al., 1989; Pesatori et al., 1994; Vie]
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From page 123... ...
TABLE 5.8 Selected Epidemiologic Studies Brain and Other CNS Tumors and Exposure to Insecticides Reference Study Population Exposed Estimated Relative Cases Risk (95% CI) Insecticides Cohort Study Morrison et al., 1992 Case-Control Studies Cocco et al., l999b Cocco et al., 1998c Musicco et al., 1988 CarladiaIl prairie farmers Female CNS deaths in 24 US states Insecticides and fungicides CNS deaths in 24 US states Pesticides other than herbicides White men White women Brain glioma patients in Milan, Italy Insecticide aIld fungicide users 5 1.34 (0.55 - 3.25)
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From page 124... ...
The potential for increased risk of NHL with exposure to specific organophosphorous insecticides has been examined in several studies. The studies were ..
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From page 125... ...
Increased risk of NHL with lindane use was observed whether or not subjects wore protective equipment when lindane was used for fewer than 4 days/year and when it was used on more than 4 days/year. When exposures to carbary1, diazinon, carbamates, and organophosphorous insecticides were controlled for in the analysis, the relative risk of NHL with lindane use was T.2 to I.5.
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From page 126... ...
were interviewed by telephone to determine individual exposure to specific agricultural chemicals. On the basis of selfreported exposure, several classes of insecticides were associated with increased risk of NHL among men, including organophosphorous insecticides (OR = 1.9, 95°/O Cl = 1.1-3.11.
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From page 127... ...
Several of the studies described above for specific insecticides also found NHL risk increased with exposure to classes of insecticides. Cantor and colleagues (1 992)
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From page 128... ...
By design, such studies assign specific exposures to individual subjects albeit without direct workplace or environmental measurements, in these studies, increased risks were observed with exposure to organophosphorous agents and carbamates in general and malathion, diazinon, lindane, and carbary} exposure in particular. However, there are too few studies with exposure measurements at the individual insecticide level to draw conclusions on any specific insecticide.
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From page 129... ...
TABLE 5.9 Selected Epidemiologic Studies Non-Hodgkin's Lymphoma and Exposure to Insecticides Reference Study Population Exposed Estimated Relative Cases Risk (95% CI) Specific Insecticides Case-Control Studies Zheng et al., 2001 Pooled analysis of NHL cases Carbaryl (farm use based on all subjects)
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From page 130... ...
. Epidemiologic Studies of Exposure to Insecticides Few studies have examined the relationship between HD and exposure to specific insecticides thought to have been used during the Gulf War.
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From page 131... ...
TABLE 5.10 Selected Epidemiologic Studies Hodgkin's Disease and Exposure to Insecticides Reference Study Population Exposed Estimated Relative Cases Risk (95% CI) Insecticides Case-Control Study Zahm et al., 1988 Residents of Kansas Insecticides (ever use)
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From page 132... ...
about specific exposure to 24 animal insecticides and 34 crop insecticides. An increased risk of MM was associated with use of dichlorvos (OR = 2.0, 95% CT = 0.~-5.0)
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From page 133... ...
On the basis of three exposed cases, a multivariate analysis revealed a slightly increased risk of MM with exposure to carbamate insecticides (as a classy for those reporting exposure at any point in time and for those who used the insecticides in their profession. Although an a priori matrix was used in assessing exposure, which probably reduced recall bias, there is still the potential for nondifferential misclassification of exposure, which would tend to reduce the risk estimate.
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From page 134... ...
TABLE 5.11 Selected Epidemiologic Studies Multiple Myeloma and Exposure to Insecticides Reference Study Population Exposed Estimated Relative Cases Risk (95% CI) Specific Insecticides Case-Control Study Brown et al., 1993 Classes of Insecticides Case-Control Studies Nanni et al., 1998 Burmeister, 1990 Insecticides Case-Control Studies Brown et al., 1993 Zahm et al., 1992 Male residents of Iowa Dichlorvos (animal use)
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From page 135... ...
. Epidemiologic Studies of Exposure to Insecticides Several studies examined the relationship between exposure to specific insecticides, classes of insecticides, and insecticides in general and the risk of adult leukemia.
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From page 136... ...
described above found an increased risk of all leukemias with ever handling pyrethrins (ORanima~ = 3.7, 95% CI = 1.3 ~ ~ ~ ~ A, ~ #_ T ~ mu, ~;~v~na~es (kJKz~nim~' = I.D, V;'-/o ~1 = U..; UKcrops = 1.4' 9)
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From page 137... ...
A majority of the studies discussed above reported an increased risk of leukemia, especially among those exposed to organophosphorous insecticides. The studies on specific organophosphorous agents, such as diazinon, dichiorvos, and malathion, as well as on the broader category of insecticides provided additional support to a conclusion on exposure to organophosphorous compounds.
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From page 138... ...
TABLE 5.12 Selected Epidemiologic Studies Adult Leukemia and Exposure to Insecticides Reference Study Population Exposed Estimated Relative Risk Cases (95% CI) Specific Insecticides Case-Control Studies Brown et al., 1990 Residents of Iowa and Minnesotaa Carbaryl Animal insecticide, ever handled 7 1.3 (0.5-3.2)
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From page 139... ...
I ~ _ aFor all data points, risk estimates for specific animal and crop insecticides are taken from analysis of ever having handled these insecticides. CHILDHOOD CANCER Childhood cancer is defined by ACS as cancer diagnosed between birth and the age of 14 years.
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From page 140... ...
Brain tumors are the second most common group of cancers affecting children, accounting for about 20% of all childhood cancers. Common types of childhood brain tumors include astrocytomas (tumors originating in the brain cells)
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From page 141... ...
Pest strips contain the active ingredient dichiorvos. The study found an increased risk of childhood leukemia in children whose mothers used pest strips during the last 3 months of pregnancy.
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From page 142... ...
for childhood leukemia and paternal or maternal occupational exposure to insecticides, herbicides, or fungicides in the year before pregnancy and during pregnancy. Two other studies of exposure to pesticides during pregnancy found increased risks of childhood leukemia (Lowengart et al., ~ 987; Shu et al., 1988)
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From page 143... ...
The following discussion highlights the issues of concern and the key studies reviewed by the committee in making its conclusion. No studies addressed exposure to specific insecticides only before conception in relation to childhood cancers other than leukemia.
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From page 144... ...
An increased risk of neuroblastoma was observed among children whose mothers reported exposure to insecticides during pregnancy (OR = 2.3, 95% CT = I.4-3.7) and whose fathers reported the same exposure (OR = I.7, 95% C} = I.~2.7~.
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From page 145... ...
TABLE 5.13 Selected Epidemiologic Studies Childhood Leukemia and Exposure to Insecticides Reference Study Population Exposed Estimated Relative Cases Risk (95% CI) Insecticides Case-Control Studies Infante-Rivard et al., 1999 ALL cases in Quebec, Canada Maternal domestic exposure 1 month before pregnancy to end of pregnancy Cockroaches, ants, flies, bees, wasps 168 1.79 (1.34-2.40)
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From page 146... ...
TABLE 5.14 Selected Epidemiologic Studies Other Childhood Cancers and Exposure to Insecticides Reference Study Population Exposed Estimated Relative Cases Risk (95% CI) Brain and Other Nervous System Tumors Case-Control Studies Daniels et al., 2001 Neuroblastoma (Children's Study Group)
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From page 147... ...
2000. Risk of pancreatic cancer and occupational exposures in Spain.
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From page 148... ...
1998b. Case-control study of occupational exposures and male breast cancer.
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From page 149... ...
1999. Serum organochlorine pesticides and PCBs and breast cancer risk: Results from a prospective analysis (USA)
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From page 150... ...
1999. Preconceptional paternal exposure to pesticides and increased risk of childhood leukaemia.
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From page 151... ...
1995. Pancreatic cancer and occupational exposures.
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From page 152... ...
1990. Occurrence of betahexachlorocyclohexane in breast cancer patients.
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From page 153... ...
1998. Occupational exposures, atlimal exposure and smoking as risk factors for hairy cell leukaemia evaluated in a case-control study.
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From page 154... ...
American Journal of Industrial Medicine 21~3~:321-330. Scherr PA, Hutchison GB, Neiman RS.
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From page 155... ...
American Journal of Industrial Medicine 18~3~:303-305. Wesseling C, Antich D, Hogstedt C, Rodriguez AC, Ahlbom A
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