Elsevier

The Lancet

Volume 352, Issue 9143, 5 December 1998, Pages 1816-1820
The Lancet

Articles
Organochlorine exposure and risk of breast cancer

https://doi.org/10.1016/S0140-6736(98)04504-8Get rights and content

Summary

Background

Some organochlorine compounds may have weak oestrogenic effects and are, therefore, suspected of increasing the risk of breast cancer. We assessed prospectively the risk of breast cancer in relation to serum concentrations of several organochlorine compounds.

Methods

In 1976, serum samples from 7712 women were obtained from participants in the Copenhagen City Heart Study as part of physical examinations and interviews about lifestyle factors. During 17 years of follow-up, 268 women developed invasive breast cancer. Each woman with breast cancer was matched with two breast-cancerfree women from the remaining cohort. We analysed in 1996–97 the serum samples from 240 women with breast cancer and 477 controls.

Findings

Dieldrin was associated with a significantly increased dose-related risk of breast cancer (adjusted odds ratio 2·05 [95% CI 1·17–3·57], p for trend 0·01). β-hexachlorocyclohexane increased risk slightly but not significantly (p for trend 0·24). There was no overall association between risk of breast cancer and p, p′dichlorodiphenyltrichloroethane or metabolites or for polychlorinated biphenyls. Exclusion of women with breast cancer diagnosed within 5 years of blood sampling strengthened the result for dieldrin, but did not affect the other results.

Interpretation

These findings support the hypothesis that exposure to xeno-oestrogens may increase the risk of breast cancer.

Introduction

Breast cancer is the most common cancer among women in many western countries. In Denmark, about 14% of all women develop breast cancer, and the incidence has more than doubled in the past 30 years.1 This trend is seen also in some developing countries with lower incidences.2 Recognised risk factors for breast cancer and improved diagnostic methods such as mammography can account for only a small part of this trend.1 Most of the risk factors for breast cancer, such as early menarche, late menopause, nulliparity, late conception of the firstborn, and hormone-replacement treatment after menopause suggest that oestrogen has a prominent role in the pathogenesis of breast cancer.3 The substantial international differences and changes in incidence of breast cancer seen among migrants highlight environmental factors.2, 4 Certain organochlorine compounds, including agricultural pesticides, such as p,p′-dichlorodiphenyltrichloroethane (DDT), chlordane, lindane, dieldrin, and industrial chemicals such as polychlorinated biphenyls, may disrupt the endocrine system.5, 6, 7 More than 15 000 organic chlorinated compounds have been or are currently used. Biological half-lives of several years have been reported in human beings for some substances, which leads to accumulation in lipid-rich tissue.8, 9 The xeno-oestrogens known so far have a much lower oestrogenic potency than oestradiol. Human beings can, however, be exposed to several compounds at the same time, and there is evidence of synergistic effects.7, 10

We investigated whether women with high serum concentrations of potentially oestrogenic compounds (kepone, dieldrin, o,p′-DDT, p,p′-DDT, and low chlorinated PCB congeners) are at increased risk of breast cancer.

Section snippets

Participants

We used information on women enrolled in the Copenhagen City Heart Study (CCHS).11, 12 The study population was selected randomly through the Civil Registration System in ten electoral constituencies around Rigshospitalet, Copenhagen, Denmark. In 1976, 49 128 women aged 20 years or older lived in these constituencies, and 21% (10 317) of these were invited to participate in the CCHS. 7712 women provided baselineinformation. Each participant filled in a standard questionnaire about lifestyle and

Results

The risk of breast cancer decreased with increasing number of full-term pregnancies, and increased with increasing bodyweight and height. Unmarried women had an 89% higher risk of breast cancer than married women. Non-significant risks were associated with physical activity and alcohol consumption, whereas there was no association with smoking, school education, and household income (table 1).

All women had measurable concentrations of at least one of the DDTs, more than 90% had detectable PCBs

Discussion

Organochlorines such as dieldrin, which has oestrogenic effects, might increase the risk of breast cancer. Previous prospective studies have given ambiguous results. In a cohort of 14 290 women from New York diagnosed with breast cancer 1–6 months after blood sampling, women with the highest serum concentrations of total PCB and DDE had a four-fold increase in the risk of breast cancer.17 Another study that followed up 57 040 women in California, USA, for about 20 years showed a similar trend,

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