Organochlorine compounds in neoplastic and adjacent apparently normal breast tissue

Wassermann, M.; Nogueira, Diogo Pupo; Tomatis, Lorenzo; Mirra, Antônio Pedro; Shibata, Hiroko; Arie, G; Cucos, Similica; D, Wassermann

doi:10.1007/bf01685076

Cited by 121 publications

(39 citation statements)

References 5 publications

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“…Several epidemiologic studies since the 1970's have examined the association between breast cancer in women and organochlorines measured either in the serum or adipose tissue. A number of these studies have been null, but others have had mixed results or findings limited to subgroups of the populations studied (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28). While DDT and PCBs were banned in the US in the 1970's, residues of DDT and PCBs continue to be detected in the blood of most Americans as they are persistent in the environment, are known to accumulate in tissue including the fatty tissue of the breast, and have long half lives (29)(30)(31).…”

Section: Introductionmentioning

confidence: 99%

Serum organochlorines and breast cancer: a case–control study among African-American women

Gatto

Longnecker

Press

et al. 2007

Cancer Causes Control

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This population-based case-control study of African-American women (355 breast cancer case patients, 327 controls) examined the association between breast cancer and circulating levels of PCBs and dichlorodiphenyldichloroethene (DDE), a metabolite of DDT. Case patients were diagnosed with invasive breast carcinoma and interviewed between June 1995 and July 1998, and control subjects were identified by random digit dialing methods. Serum levels of DDE and total PCBs were adjusted for total lipid content. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable unconditional logistic regression methods. Effect modification by tumor receptor status and cancer treatment was investigated. Breast cancer risk was not associated with increasing quintiles of lipid-adjusted PCBs or DDE (highest vs. lowest quintile adjusted for age, body mass index (BMI) and breastfeeding for DDE: OR=1.02, 95% CI=(0.61, 1.72), p-trend = 0.74; for PCBs: OR=1.01, 95% CI=(0.63, 1.63), p-trend = 0.56). Risk did not differ by strata of BMI, breastfeeding, parity, menopausal status or tumor receptor status. This study, the largest study of African-American women to date, does not support a role of DDE and total PCBs in breast cancer risk at the levels measured.

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Section: Introductionmentioning

confidence: 99%

Serum organochlorines and breast cancer: a case–control study among African-American women

Gatto

Longnecker

Press

et al. 2007

Cancer Causes Control

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“…Polychlorinated biphenyls (PCBs), dioxins, and p,p´-dichlorodiphenyltrichloroethane (DDT) are lipophilic organochlorines, they accumulate in fat, and they are present at the µg to mg/kg levels in human tissues and milk (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27), confirming direct exposure of the mammary tissues. Some epidemiologic investigations have found no association, or even a negative one, between human tissue levels of PCB congeners, DDT, and p,p´-dichlorodiphenyldichloroethene (DDE) and breast cancer (28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38); but in specific subpopulations (7,22,29,33,34,(39)(40)(41)(42) or by testing specific congeners (27,33,43,44), some did detect significant associations. The hypothesis of a link between organochlorine exposure and breast cancer is challenged by the study of accidentally exposed populations.…”

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confidence: 99%

Modulatory effects of neonatal exposure to TCDD, or a mixture of PCBs, p,p'-DDT, and p-p'-DDE, on methylnitrosourea-induced mammary tumor development in the rat.

Desaulniers

Leingartner

Russo

et al. 2001

Environ Health Perspect

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The role of organochlorine (OC) exposure in the etiology of breast cancer remains controversial. Thus, our objective was to determine whether the most abundant and toxic OCs found in human milk could, when ingested during the neonatal period, modulate the development of mammary tumors in the rat. We prepared a mixture composed of p,p'-dichlorodiphenyltrichloroethane (DDT), its major metabolite, p,p'-dichlorodiphenyldichloroethene (DDE), and 19 polychlorinated biphenyls (PCB) based on their concentrations found in the milk of Canadian women. Neonate rats at 1, 5, 10, 15, and 20 days of age were gavaged with this mixture, at 10, 100, and 1,000 times the amount that a human baby would consume. An additional group received 2.5 microg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)/kg body weight (bw) by gavage at 18 days of age, instead of the mixture. On day 21, all treatment groups, except for a control group and a 1,000-mix group, received a single intraperitoneal injection of methylnitrosourea (MNU, 30 mg/kg bw), the initiator of the carcinogenic process. The average number of rats per treatment group was 33. Rats were sacrificed when their tumors reached 1 cm in size, or at 308 days of age. We prepared mammary tumors and mammary gland whole mounts for histologic analysis. There were no significant effects when only the malignant or only the benign tumors were considered. After all benign and malignant lesions were pooled, the number of mammary tumors differed among all MNU-treated groups (p = 0.02) with more lesions developing in the MNU-1,000[times] (median = 4.5; p = 0.05) and MNU-TCDD (median = 5.5; p = 0.07) compared to the MNU-0 rats (median = 2). Compared to the MNU-0 group, the percentage of rats that developed palpable tumors (benign plus malignant) was slightly higher (p = 0.06) in the MNU-TCDD group, but not in the MNU-1,000[times] group. The percentage of palpable tumors that were malignant was higher (p = 0.02) in the MNU-100[times] group (15/16, 94%) than in the MNU-0 group (10/18, 56%). The highest dose of the mixture delayed (p = 0.03) the development of tumors, but this was not observed with the MNU-TCDD treatment. These results suggest that neonatal exposure to high doses of organochlorines could favor the development of MNU-induced mammary lesions, but also delays the development of palpable tumors in the rat.

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“…A case-control study on pancreatic cancer found a strong dose-related association with exposure to DDT (7) although its positive results have not been replicated thus far. Breast cancer risk has also been repeatedly associated with increased adipose and serum levels of DDE in the general population (8)(9)(10)(11), although more recent studies yield contradictory or negative results (12)(13)(14)(15)(16). The p,p'-DDE concentration was elevated in the tumor tissue of patients suffering from uterine cancer as compared to the surrounding normal tissue (17), although the risk of endometrial cancer was not increased in relation to serum pp'-DDE concentrations (18).…”

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Cancer mortality and environmental exposure to DDE in the United States.

Cocco

Kazerouni

Zahm

2000

Environ Health Perspect

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To explore the role of DDE, the major and most persistent DDT derivative, in cancer etiology, we examined the association of the 1968 adipose DDE levels of population samples from 22 U.S. states with age-adjusted mortality rates between 1975 and 1994 for multiple mycloma; nonHodgkin lymphoma (NHL); and cancer of the breast, corpus uteri, liver, and pancreas. Separate analyses were conducted by gender and race. Covariates in the ression models induded average per-capita income, percent metropolitan residents, and the population density. Liver cancer mortality increased significantly with adipose DDE levels in both sexes among whites, but not among African Americans. No association was observed for pancreatic cancer and multiple myeloma. Breast cancer mortality was inversely correlated with adipose DDE levels amrong both white and African American women. Significant inverse correlations were also observed for uterine cancer among white women, whereas no association was observed for African Americans and for NHL among whites (men and women) and African American women. The results for pancreatic cancer, multiple myeloma, NHL, breast cancer, and uterine cancer did not support the hypothesis of an association with past adipose levels of the DDT derivative DDE. The multivariate analysis confirmed most findings. The association between liver cancer and DDE observed among whites, particularly in view of the occurrence of hepatic neoplasms in laboratory animals exposed to DDT, warrants fiurther investigation. Key word breast cancer, cancer of the corpus uteri, DDE, DDT, environment, epidemiology, liver cancer, multiple myeloma, non-Hodgkin lymphoma, pancreatic cancer.

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Organochlorine compounds in neoplastic and adjacent apparently normal breast tissue

Cited by 121 publications

References 5 publications

Serum organochlorines and breast cancer: a case–control study among African-American women

Serum organochlorines and breast cancer: a case–control study among African-American women

Modulatory effects of neonatal exposure to TCDD, or a mixture of PCBs, p,p'-DDT, and p-p'-DDE, on methylnitrosourea-induced mammary tumor development in the rat.

Cancer mortality and environmental exposure to DDE in the United States.

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