Cancer Risks

Avila-Vazquez et al., 2015

Medardo Avila-Vazquez, Agustina Etchegoyen, Eduardo Maturano and Luciana Ruderman, “Cancer and detrimental reproductive effects in an Argentine agricultural community environmentally exposed to glyphosate,” The Journal of Biological Physics and Chemistry, 2015, 15:3, DOI: 10.4024/09VA15A.jbpc.15.03

ABSTRACT:

Argentina utilizes about 200 000 tonnes of glyphosate for its agriculture each year. People living near the fields treated with glyphosate often mention an increase in cancer and reproductive alterations. In Monte Maiz, an agricultural settlement with approximate population 8000, we conducted an environmental test assessing water, soil and particulate material contamination as well as an epidemiological study to detect and locate cases of cancer, abortion and genetic abnormality. The site utilizes annually 650 tonnes of glyphosate applied over an area of 65 000 ha. The glyphosate is concentrated and prepared for dispersal in the settlement. We detected glyphosate in particulate material and grain husks and it was found to be present at an even higher concentration on the ground in the village than in the surrounding rural area. The rate of spontaneous abortion in Monte Maiz is three times higher than the national average and the rate of occurrence of genetic abnormality is about twice the national average. Cancer occurrence is between two and three times the reference values for the entire nation with regard to incidence, prevalence and mortality. Although it is of course impossible to establish direct causality, the indicators that emerge from the correlated variables strongly suggest a public health problem of significant proportions, requiring immediate attention.

 

Avila-Vazquez et al., 2017

Medardo Avila-Vazquez, Eduardo Maturano, Agustina Etchegoyen, Flavia Silvina Difilippo, Bryan Maclean, “Association between Cancer and Environmental Exposure to Glyphosate,” International Journal of Clinical Medicine, 2017, 8:2, DOI: 10.4236/ijcm.2017.82007

ABSTRACT:

BACKGROUND: Argentina, Brazil, Paraguay and Uruguay farm transgenic seeds glyphosate resistant. Argentina annually utilizes 240,000 tonnes of glyphosate in agriculture. A change in the profile of morbidity and mortality is perceived in agricultural areas; cancer seems to prevail. Monte Maíz is a typical argentine agricultural town with 8000 inhabitants; the Mayor and residents of Monte Maiz requested an environmental health study due to perceived increase in cancer frequencies.

METHODS: An exploratory ecological study was developed to assess the urban environmental contamination and the frequencies and distribution of cancer through an environmental analysis of pollution sources including measurements of pesticides in water, soil and grain dust, and a cross-sectional study of cancer patients that explore associations with different variables.

RESULTS: Glyphosate was detected in soil and grain dust and was found to be at an even higher concentration in the village soil than in the rural area. 650 tonnes are used annually in the region and manipulated inner town. We do not find other relevant sources of pollution. Cancer incidence, prevalence, and mortality are between two and three times higher than the reference values (Globocan 2012, WHO) for the entire nation (706/100,000 persons vs. 217/100,000; 2123/100,000 persons vs. 883.82/100,000 and 383/100,000 persons vs. 115.13/100,000, respectively).

CONCLUSION: This study detects high glyphosate pollution in association with increased frequencies of cancer in a typical argentine agricultural village, and by design, cannot make claims of causality. Other study designs are required, but if we corroborate the concrescence of high exposure to glyphosate and cancer. FULL TEXT

Band et al., 2011

Band PR, Abanto Z, Bert J, Lang B, Fang R, Gallagher RP, Le ND., “Prostate cancer risk and exposure to pesticides in British Columbia farmers,” Prostate, 2011, 71:2, DOI: 10.1002/pros.21232.

ABSTRACT:

BACKGROUND: Several epidemiologic studies have reported an increased risk of prostate cancer among farmers. Our aim was to assess the risk of developing prostate cancer in relation to exposure to specific active compounds in pesticides.

METHOD: A case-control approach was used with 1,516 prostate cancer patients and 4,994 age-matched internal controls consisting of all other cancer sites excluding lung cancer and cancers of unknown primary site. Lifetime occupational history was obtained through a self-administered questionnaire and used in conjunction with a job exposure matrix to estimate the participants’ lifetime cumulative exposure to approximately 180 active compounds in pesticides. Conditional logistic regression was used to assess prostate cancer risk, adjusting for potential confounding variables and effect modifiers. These include age, ethnicity, alcohol consumption, smoking, education, and proxy respondent.

RESULTS AND CONCLUSIONS: The significant association between prostate cancer risk and exposure to DDT (OR = 1.68; 95% CI: 1.04-2.70 for high exposure), simazine (OR = 1.89; 95% CI: 1.08-3.33 for high exposure), and lindane (OR = 2.02; 95% CI: 1.15-3.55 for high exposure) is in keeping with those previously reported in the literature. We also observed a significant excess risk for several active ingredients that have not been previously reported in the literature such as dichlone, dinoseb amine, malathion, endosulfan, 2,4-D, 2,4-DB, and carbaryl. Some findings in our study were not consistent with those reported in the literature, including captan, dicamba, and diazinon. It is possible that these findings showed a real association and the inconsistencies reflected differences of characteristics between study populations.

Benbrook, 2016c

John Peterson Myers, Michael N. Antoniou, Bruce Blumberg, Lynn Carroll, Theo Colborn, Lorne G. Everett, Michael Hansen, Philip J. Landrigan, Bruce P. Lanphear, Robin Mesnage, Laura N. Vandenberg, Frederick S. vom Saal, Wade V. Welshons and Charles M. Benbrook. “Concerns over use of glyphosate-based herbicides and risks associated with exposures: a consensus statement,” Environmental Health, 2016, 15:19, DOI: 10.1186/s12940-016-0117-0.

ABSTRACT:

The broad-spectrum herbicide glyphosate (common trade name “Roundup”) was first sold to farmers in 1974. Since the late 1970s, the volume of glyphosate-based herbicides (GBHs) applied has increased approximately 100-fold. Further increases in the volume applied are likely due to more and higher rates of application in response to the widespread emergence of glyphosate-resistant weeds and new, pre-harvest, dessicant use patterns. GBHs were developed to replace or reduce reliance on herbicides causing well-documented problems associated with drift and crop damage, slipping efficacy, and human health risks. Initial industry toxicity testing suggested that GBHs posed relatively low risks to non-target species, including mammals, leading regulatory authorities worldwide to set high acceptable exposure limits. To accommodate changes in GBH use patterns associated with genetically engineered, herbicide-tolerant crops, regulators have dramatically increased tolerance levels in maize, oilseed (soybeans and canola), and alfalfa crops and related livestock feeds. Animal and epidemiology studies published in the last decade, however, point to the need for a fresh look at glyphosate toxicity. Furthermore, the World Health Organization’s International Agency for Research on Cancer recently concluded that glyphosate is “probably carcinogenic to humans.” In response to changing GBH use patterns and advances in scientific understanding of their potential hazards, we have produced a Statement of Concern drawing on emerging science relevant to the safety of GBHs. Our Statement of Concern considers current published literature describing GBH uses, mechanisms of action, toxicity in laboratory animals, and epidemiological studies. It also examines the derivation of current human safety standards. We conclude that: (1) GBHs are the most heavily applied herbicide in the world and usage continues to rise; (2) Worldwide, GBHs often contaminate drinking water sources, precipitation, and air, especially in agricultural regions; (3) The half-life of glyphosate in water and soil is longer than previously recognized; (4) Glyphosate and its metabolites are widely present in the global soybean supply; (5) Human exposures to GBHs are rising; (6) Glyphosate is now authoritatively classified as a probable human carcinogen; (7) Regulatory estimates of tolerable daily intakes for glyphosate in the United States and European Union are based on outdated science. We offer a series of recommendations related to the need for new investments in epidemiological studies, biomonitoring, and toxicology studies that draw on the principles of endocrinology to determine whether the effects of GBHs are due to endocrine disrupting activities. We suggest that common commercial formulations of GBHs should be prioritized for inclusion in government-led toxicology testing programs such as the U.S. National Toxicology Program, as well as for biomonitoring as conducted by the U.S. Centers for Disease Control and Prevention.  FULL TEXT

Cabello et al., 2001

Gertrudis Cabello, Mario Valenzuela, Arnaldo Vilaxa, Viviana Durán, Isolde Rudolph, Nicolas Hrepic, and Gloria Calaf, “A Rat Mammary Tumor Model Induced by the Organophosphorous Pesticides Parathion and Malathion, Possibly through Acetylcholinesterase Inhibition,” Environmental Health Perspectives, 2001, 109:5.

ABSTRACT:

Environmental chemicals may be involved in the etiology of breast cancers. Many studies have addressed the association between cancer in humans and agricultural pesticide exposure. Organophosphorous pesticides have been used extensively to control mosquito plagues. Parathion and malathion are organophosphorous pesticides extensively used to control a wide range of sucking and chewing pests of field crops, fruits, and vegetables. They have many structural similarities with naturally occurring compounds, and their primary target of action in insects is the nervous system; they inhibit the release of the enzyme acetylcholinesterase at the synaptic junction. Eserine, parathion, and malathion are cholinesterase inhibitors responsible for the hydrolysis of body choline esters, including acetylcholine at cholinergic synapses. Atropine, a parasympatholytic alkaloid, is used as an antidote to acetylcholinesterase inhibitors. The aim of this study was to examine whether pesticides were able to induce malignant transformation of the rat mammary gland and to determine whether alterations induced by these substances increase the cholinergic activation influencing such transformation. These results showed that eserine, parathion, and malathion increased cell proliferation of terminal end buds of the 44-day-old mammary gland of rats, followed by formation of 8.6, 14.3, and 24.3% of mammary carcinomas, respectively, after about 28 months. At the same time, acetylcholinesterase activity decreased in the serum of these animals from 9.78 +/- 0.78 U/mL in the control animals to 3.05 +/- 0.06 U/mL; 2.57 +/- 0.15 U/mL; and 3.88 +/- 0.44 U/mL in the eserine-, parathion-, and malathion-treated groups, respectively. However, atropine alone induced a significant (p < 0.05) decrease in the acetylcholinesterase activity from the control value of 9.78 +/- 0.78 to 4.38 +/- 0.10 for atropine alone, to 1.32 +/- 0.06 for atropine in combination with eserine, and 2.39 +/- 0.29 for atropine with malathion, and there was no mammary tumor formation. These results indicate that organophosphorous pesticides induce changes in the epithelium of mammary gland influencing the process of carcinogenesis, and such alterations occur at the level of nervous system by increasing the cholinergic stimulation. FULL TEXT

Cohn et al., 2007

Cohn BA, Wolff MS, Cirillo PM, Sholtz RI, “DDT and breast cancer in young women: new data on the significance of age at exposure,” Environmental  Health Perspectives, 2007, 115:10.

ABSTRACT:

BACKGROUND: Previous studies of DDT and breast cancer assessed exposure later in life when the breast may not have been vulnerable, after most DDT had been eliminated, and after DDT had been banned.

OBJECTIVES: We investigated whether DDT exposure in young women during the period of peak DDT use predicts breast cancer.

METHODS: We conducted a prospective, nested case-control study with a median time to diagnosis of 17 years using blood samples obtained from young women during 1959-1967. Subjects were members of the Child Health and Development Studies, Oakland, California, who provided blood samples 1-3 days after giving birth (mean age, 26 years). Cases (n = 129) developed breast cancer before the age of 50 years. Controls (n = 129) were matched to cases on birth year. Serum was assayed for p,p’-DDT, the active ingredient of DDT; o,p’-DDT, a low concentration contaminant; and p,p’-DDE, the most abundant p,p’-DDT metabolite.

RESULTS: High levels of serum p,p’-DDT predicted a statistically significant 5-fold increased risk of breast cancer among women who were born after 1931. These women were under 14 years of age in 1945, when DDT came into widespread use, and mostly under 20 years as DDT use peaked. Women who were not exposed to p,p’-DDT before 14 years of age showed no association between p,p’-DDT and breast cancer (p = 0.02 for difference by age).

CONCLUSIONS: Exposure to p,p’-DDT early in life may increase breast cancer risk. Many U.S. women heavily exposed to DDT in childhood have not yet reached 50 years of age. The public health significance of DDT exposure in early life may be large.  FULL TEXT

Cohn et al., 2015

Cohn BA, La Merrill M, Krigbaum NY, Yeh G, Park JS, Zimmermann L, Cirillo PM, “DDT Exposure in Utero and Breast Cancer,” Journal of Clinical Endocrinology and Metabolism, 2015, 100:8, doi: 10.1210/jc.2015-1841.

ABSTRACT:

CONTEXT: Currently no direct evidence links in utero dichlorodiphenyltrichloroethane (DDT) exposure to human breast cancer. However, in utero exposure to another xenoestrogen, diethylstilbestrol, predicts an increased breast cancer risk. If this finding extends to DDT, it could have far-reaching consequences. Many women were heavily exposed in utero during widespread DDT use in the 1960s. They are now reaching the age of heightened breast cancer risk. DDT exposure persists and use continues in Africa and Asia without clear knowledge of the consequences for the next generation.

HYPOTHESIS: In utero exposure to DDT is associated with an increased risk of breast cancer.

DESIGN: This was a case-control study nested in a prospective 54-year follow-up of 9300 daughters in the Child Health and Development Studies pregnancy cohort (n = 118 breast cancer cases, diagnosed by age 52 y and 354 controls matched on birth year).

SETTING AND PARTICIPANTS: Kaiser Foundation Health Plan members who received obstetric care in Alameda County, California, from 1959 to 1967, and their adult daughters participated in the study.

MAIN OUTCOME MEASURE: Daughters’ breast cancer diagnosed by age 52 years as of 2012 was measured.

RESULTS: Maternal o,p’-DDT predicted daughters’ breast cancer (odds ratio fourth quartile vs first = 3.7, 95% confidence interval 1.5-9.0). Mothers’ lipids, weight, race, age, and breast cancer history did not explain the findings.

CONCLUSIONS: This prospective human study links measured DDT exposure in utero to risk of breast cancer. Experimental studies are essential to confirm results and discover causal mechanisms. Findings support classification of DDT as an endocrine disruptor, a predictor of breast cancer, and a marker of high risk.  FULL TEXT

De Roos et al., 2003

A J De Roos, S Zahm, K Cantor, D Weisenburger, F Holmes, L Burmeister, and A Blair, “Integrative assessment of multiple pesticides as risk factors for non-Hodgkin’s lymphoma among men,” Occupational and Environmental Medicine, 2003, 60:9, DOI: 10.1136/oem.60.9.e1

ABSTRACT:

METHODS: During the 1980s, the National Cancer Institute conducted three case-control studies of NHL in the midwestern United States. These pooled data were used to examine pesticide exposures in farming as risk factors for NHL in men. The large sample size (n = 3417) allowed analysis of 47 pesticides simultaneously, controlling for potential confounding by other pesticides in the model, and adjusting the estimates based on a prespecified variance to make them more stable.

RESULTS: Reported use of several individual pesticides was associated with increased NHL incidence, including organophosphate insecticides coumaphos, diazinon, and fonofos, insecticides chlordane, dieldrin, and copper acetoarsenite, and herbicides atrazine, glyphosate, and sodium chlorate. A subanalysis of these “potentially carcinogenic” pesticides suggested a positive trend of risk with exposure to increasing numbers.

CONCLUSION: Consideration of multiple exposures is important in accurately estimating specific effects and in evaluating realistic exposure scenarios.  FULL TEXT

De Roos et al., 2005

Anneclaire J. De Roos, Aaron Blair, Jennifer A. Rusiecki, Jane A. Hoppin, Megan Svec, Mustafa Dosemeci, Dale P. Sandler, and Michael C. Alavanja, “Cancer Incidence among Glyphosate-Exposed Pesticide Applicators in the Agricultural Health Study,” Environmental Health Perspectives, 2005, 113, DOI: 10.1289/EHP.7340.

ABSTRACT:

Glyphosate is a broad-spectrum herbicide that is one of the most frequently applied pesticides in the world. Although there has been little consistent evidence of genotoxicity or carcinogenicity from in vitro and animal studies, a few epidemiologic reports have indicated potential health effects of glyphosate. We evaluated associations between glyphosate exposure and cancer incidence in the Agricultural Health Study (AHS), a prospective cohort study of 57,311 licensed pesticide applicators in Iowa and North Carolina. Detailed information on pesticide use and other factors was obtained from a self-administered questionnaire completed at time of enrollment (1993–1997). Among private and commercial applicators, 75.5% reported having ever used glyphosate, of which > 97% were men. In this analysis, glyphosate exposure was defined as a) ever personally mixed or applied products containing glyphosate; b) cumulative lifetime days of use, or “cumulative exposure days” (years of use × days/year); and c) intensity-weighted cumulative exposure days (years of use × days/year × estimated intensity level). Poisson regression was used to estimate exposure–response relations between glyphosate and incidence of all cancers combined and 12 relatively common cancer subtypes. Glyphosate exposure was not associated with cancer incidence overall or with most of the cancer subtypes we studied. There was a suggested association with multiple myeloma incidence that should be followed up as more cases occur in the AHS. Given the widespread use of glyphosate, future analyses of the AHS will allow further examination of long-term health effects, including less common cancers. FULL TEXT

Di Renzo et al., 2015

Gian Carlo Di Renzo, Jeanne A. Conry, Jennifer Blake, Mark S. DeFrancesco, Nathaniel DeNicola, James N. Martin Jr., Kelly A. McCue, David Richmond, Abid Shah, Patrice Sutton, Tracey J. Woodruff, Sheryl Ziemin van der Poel, Linda C. Giudice, “International Federation of Gynecology and Obstetrics opinion on reproductive health impacts of exposure to toxic environmental chemicals,” International Journal of Gynecology and Obstetrics, 2015, 131, DOI: 10.1016/j.ijgo.2015.09.002

ABSTRACT:

Exposure to toxic environmental chemicals during pregnancy and breastfeeding is ubiquitous and is a threat to healthy human reproduction. There are tens of thousands of chemicals in global commerce, and even small exposures to toxic chemicals during pregnancy can trigger adverse health consequences. Exposure to toxic environmental chemicals and related health outcomes are inequitably distributed within and between countries; universally, the consequences of exposure are disproportionately borne by people with low incomes. Discrimination, other social factors, economic factors, and occupation impact risk of exposure and harm. Documented links between prenatal exposure to environmental chemicals and adverse health outcomes span the life course and include impacts on fertility and pregnancy, neurodevelopment, and cancer. The global health and economic burden related to toxic environmental chemicals is in excess of millions of deaths and billions of dollars every year. On the basis of accumulating robust evidence of exposures and adverse health impacts related to toxic environmental chemicals, the International Federation of Gynecology and Obstetrics (FIGO) joins other leading reproductive health professional societies in calling for timely action to prevent harm. FIGO recommends that reproductive and other health professionals advocate for policies to prevent exposure to toxic environmental chemicals, work to ensure a healthy food system for all, make environmental health part of health care, and champion environmental justice. FULL TEXT