Abstract
-
Objectives
This study extended and updated a meta-analysis of the association between exposure to dichlorodiphenyltrichloroethane (DDT) and the risk of breast cancer.
-
Methods
We reviewed the published literature on exposure to DDE and breast cancer risk to update a meta-analysis from 2004. The total of 35 studies included 16 hospital-based case–control studies, 11 population-based case–control studies, and 10 nested case–control studies identified through keyword searches in the PubMed and EMBASE databases.
-
Results
The summary odds ratio (OR) for the identified studies was 1.03 (95% confidence interval 0.95–1.12) and the overall heterogeneity in the OR was observed (I2 = 40.9; p = 0.006). Subgroup meta-analyses indicated no significant association between exposure to DDE and breast cancer risk by the type of design, study years, biological specimen, and geographical region of the study, except from population-based case–control studies with estimated DDE levels in serum published in 1990s.
-
Conclusion
Existing studies do not support the view that DDE increases the risk of breast cancer in humans. However, further studies incorporating more detailed information on DDT exposure and other potential risk factors for breast cancer are needed.
-
Keywords:
Keywords
breast cancer; dichlorodiphenyldichloroethylene; meta-analysis; pesticide exposure; systematic review
Introduction
Dichlorodiphenyltrichloroethane (DDT) is a synthetic chemical that includes
p,
p′-dichlorodiphenyltrichloroethane (
p,
p′-DDT),
p,
p′-dichlorodiphenyldichloroethylene (
p,
p′-DDE), and
p,
p′-dichlorodiphenyldichloroethane (
p,
p′-DDD or
p,
p′-TDE). DDE (dichlorodiphenyldichloroethylene) is the main metabolite of DDT, which is rapidly converted into DDE in biological systems
[1]. After identifying its insecticidal function, DDT was widely used to prevent malaria and some agricultural pests worldwide. Although the use of DDT was banned in most developed countries in the early 1970s, DDT was still used in some developing countries, such as India, Indonesia, and Mexico, until the 1990s to control the mosquitoes that cause malaria
[1,2].
DDT is bioaccumulated in the lipid component of biological systems through the food chain because it is highly lipophilic and is resistant to degradation. Therefore, despite its prohibition in many countries, DDT is still present in the environment and the food chain. DDE in particular has a very long half-life and is of toxicological importance. The half-lives of DDT and DDE in humans have been estimated to be between 6 years and 10 years
[3]. The DDT and DDE accumulated in the lipid components, such as adipose tissue, are slowly released into the bloodstream
[4]. DDT and its metabolites have been associated with adverse effects including obesity, type 2 diabetes mellitus, and carcinogenicity
[5–7]. These chemicals can affect various tissues through mechanisms involving the steroidogenic pathway such as antiandrogenic or estrogenic activity, and receptor-mediated changes in protein synthesis
[8–10].
Since DDT and DDE were first reported to be related to breast cancer in 1993
[11], there has been increased attention on the association between exposure to DDT and the risk of breast cancer. Although many epidemiological studies have been conducted to investigate the relationship between DDT exposure and breast cancer risk, there is a large heterogeneity between studies and the findings are not conclusive. Because a meta-analysis study showed no evidence of an association between DDT exposure and breast cancer risk
[12], several new epidemiological studies have been published about the relationship between the body burden of DDT and breast cancer risk
[13–18].
In the work reported here, we aimed to provide an update of a systematic review and meta-analysis to estimate the association between DDE exposure and the risk of breast cancer based on study characteristics.
Materials and methods
2.1 Study selection
We searched and reviewed the PubMed and EMBASE databases to identify eligible epidemiological studies published in English up to August 2012 using selected common keywords related to DDT exposure and the risk of breast cancer. The reference lists of the identified papers and previous literature reviews were carefully examined for additional studies. The combination of keywords such as DDT, chlorphenotane, dichlorodiphenyldichloroethylene, DDE, p,p′-DDE, 1,1-dichloro-2,2-bis(4 chlorophenyl)ethylene, hydrocarbons, chlorinated, organochlorines, organochlorine pesticides, breast cancer, and breast neoplasm were entered as both medical subject heading (MeSH) terms and text words. The subject of the papers was limited to humans for all databases. We included epidemiological studies that met the following criteria: (1) studies that presented original data from case–control or cohort studies; (2) the outcome of interest was clearly defined as breast cancer; (3) the exposure of interest was DDT or DDT metabolites; and (4) studies that provided measurements with relative risk estimates and 95% confidence intervals (CIs), odds ratios (ORs) and 95% CIs, or values in cells of a 2 × 2 table (e.g., number of cases and controls in exposure categories from which the OR could be calculated). If the data were duplicated or shared in more than one study, only the most recent or more comprehensive study was included in the analysis.
2.2 Data extraction
All studies for which an abstract was present were reviewed and extracted independently by two evaluators (E.S.C. and Y.K.) according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines
[19]. Disagreements between evaluators about selected studies were resolved by discussion. The following data were extracted from the eligible studies and included in the final analysis: first author's name, publication year, study years, country, study design, number of participants (cases and controls), type of biological specimen, and OR with 95% CIs for association between the exposure of DDT and breast cancer.
2.3 Statistical analysis
Meta-analytic techniques that weight the logarithm of the OR of each study by a function of its variance were used to calculate a summary estimate. Meta-analyses were performed on the total data set and separately for the type of design (hospital-based case–control, population-based case–control, and nested case–control), study years (2000s, 1990s, 1980s, 1970s, and 1960s), biological specimen (serum, plasma, and adipose tissue), and geographical region of the study (North America, Europe, Asia, and South America). A random effect model was used to estimate pooled ORs regarding the potential heterogeneity of the study populations. Statistical heterogeneity between studies was assessed with the
Q-statistics and quantified by
I2, which measured the percentage of total variation in included studies
[20]. Significant heterogeneity was defined as the
Q-statistics test
p < 0.1 or
I2 greater than 50%. We assessed potential publication bias by examining funnel plots and using Egger's test. All the statistical analyses were performed using the Stata 12.0 software (StataCorp, College Station, TX, USA).
Results
The PubMed and EMBASE search yielded 530 papers and 44 papers remained after screening based on the inclusion criteria. On reviewing of the full text of the remaining 44 papers, we identified 35 papers on the exposure to DDE and the risk of breast cancer. Two papers each consisted of two subpopulations and we treated the data of each subgroup as a separate study (
Figure 1).
Table 1 gives the details of the 35 studies that were included in the meta-analysis. All were case–control studies and of these 10 were prospective (nested case–control) and 16 were hospital based case–control studies, and 11 were population based case–control studies, which consist of 8160 cases and 9280 controls. Five studies indicated a significant positive association with the risk of breast cancer, whereas no significant association was observed in 32 studies. Twenty-two studies conducted in the USA and Canada, eight in Europe, three in Asia, and four in South America. In most studies, the level of DDE was measured in serum samples.
Overall, there was no significant association between the exposure to DDE and the risk of breast cancer in the meta-analysis of all case–control studies (OR 1.03, 95% CI 0.95–1.12;
Figure 2A) and there was some evidence for heterogeneity (
p = 0.006,
I2 = 40.9). However, no significant publication bias was observed in the selected studies (Begg's funnel plot was symmetric; Egger's test,
p for bias = 0.145;
Figure 2B).
To resolve the heterogeneity, we performed subgroup meta-analyses by the type of study design, study years, type of biological specimen, and country (
Table 2). We found a borderline statistically significant summary OR for population-based case–control studies with 1.19 (95% CI 0.99–1.44), although there was a considerable heterogeneity based on the 11 studies (
I2 = 61.3). However, there was no significant association in other subgroup meta-analysis.
Figure 3 shows the subgroup meta-analysis for population-based case-control studies with estimated DDE levels in serum published in 1990s. The OR for this subgroup indicated 1.28 (95% CI 1.00–1.65;
Figure 3A), although there was a high heterogeneity (
Figure 3B). In other stratified meta-analyses, there was no significant association between exposure to DDE and the risk of breast cancer (data not shown).
Discussion
We found that there was no significant evidence of an association between the risk of breast cancer and exposure to DDE with recent published literature. Subgroup meta-analyses by the type of design, study years, biological specimen, and geographical region of study also do not support a relationship between exposure to DDE and the risk of breast cancer. However, population-based case–control studies with estimated DDE levels in serum and published in the 1990s showed marginally significant findings, which need further investigation.
Many studies did not report an increased risk, despite the first publication reporting an excess of breast cancer associated with exposure to DDE
[11]. Five studies
[11,14,18,21,22] among the 35 pooled studies included in our meta-analysis found a positive association between exposure to DDE and the risk of breast cancer. There was moderate heterogeneity among the pooled studies. The inconsistency and heterogeneity of the studies could be explained by potential confounders or modifiers that might affect the relationship between DDE and the risk of breast cancer. One potential explanation for the huge differences in the risk of breast cancer and the moderate heterogeneity among pooled studies is that there is a delayed time between exposure and diagnosis. As DDT can remain in the body for a long period, there is a limitation to identifying accurately the exposure period and levels of exposure.
As DDT crosses the placenta to the fetus and is secreted in breast milk
[23], human exposure begins during the early prenatal period and continues during the breastfeeding neonatal period. Evidence for DDE release from fat storage tissue in humans has been provided by breastfeeding studies, which have been found to decrease the risk of breast cancer
[24,25]. Exposure during the prenatal and neonatal periods may reduce the distinction between the exposed and unexposed groups and make it harder for such studies to show a true causal association. The age at exposure to chemicals such as DDE is also an important modifier in explaining the relationship between exposure and the risk of disease. Cohn et al
[27] reported that DDT was associated with breast cancer only for women potentially exposed at a young age (prior to 14 years of age). Thus the relationship between age at exposure to DDT and breast cancer represents an important area in need of further research.
The other limitation is combined exposure with other chemicals in the natural environment. Many persistent organic pollutants, including DDT, are known or suspected to be endocrine disruptors. However, these chemicals do not all have the same effect; some chemicals have an agonistic role in estrogenic effects, but others have an antagonistic role. Thus current estimations may rule out the possibility that there is a particular hazard from these mixtures or one chemical, whereas exposure to several different chemicals may have a pronounced effect due to their combination.
In summary, our meta-analysis found no evidence that there is an association between exposure to DDE and the risk of breast cancer. Although our results indicate no relationship, there are still several limitations to this study, such as the delay time between exposure and diagnosis, age of exposure, the effect of susceptible populations, and combined exposure with other potential carcinogens. It is particularly important to recommend studying the relationship between DDT and breast cancer based on age of exposure and combined exposure to a number of potential carcinogens.
Conflicts of interest
All contributing authors declare no conflicts of interest.
AcknowledgementsAcknowledgments
This research was supported by a grant (12161MFDS767) from Ministry of Food and Drug Safety, Osong, Korea in 2012.
Article information
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
References
- 1. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological profile for DDT, DDE, and DDD. 2002 Sep. http://www.atsdr.cdc.gov/toxprofiles/tp35-p.pdf. [accessed 13.02.14].
- 2. Turusov V., Rakitsky V., Tomatis L.. Dichlorodiphenyltrichloroethane (DDT): ubiquity, persistence, and risks. Environ Health Perspect 110(2). 2002 Feb;125−128.
- 3. Wolff M.S.. Half-lives of organochlorines (OCs) in humans [Letter]. Arch Environ Contam Toxicol 36(4). 1999 May;504.
- 4. Lim J.S., Son H.K., Park S.K.. Inverse associations between long-term weight change and serum concentrations of persistent organic pollutants. Int J Obes (Lond) 35(5). 2011 May;744−747.
- 5. Elobeid M.A., Padilla M.A., Brock D.W.. Endocrine disruptors and obesity: an examination of selected persistent organic pollutants in the NHANES 1999–2002 data. Int J Environ Res Public Health 7(7). 2010 Jul;2988−3005.
- 6. Everett C.J., Frithsen I.L., Diaz V.A.. Association of a polychlorinated dibenzo-p-dioxin, a polychlorinated biphenyl, and DDT with diabetes in the 1999–2002 National Health and Nutrition Examination Survey. Environ Res 103(3). 2007 Mar;413−418.
- 7. Beard J.. DDT and human health. Sci Total Environ 355(1–3). 2006 Feb;78−89.
- 8. Kelce W.R., Stone C.R., Laws S.C.. Persistent DDT metabolite p,p'-DDE is a potent androgen receptor antagonist. Nature 375(6532). 1995 Jun;581−585.
- 9. Steinmetz R., Young P.C., Caperell-Grant A.. Novel estrogenic action of the pesticide residue beta-hexachlorocyclohexane in human breast cancer cells. Cancer Res 56(23). 1996 Dec;5403−5409.
- 10. Lemaire G., Mnif W., Mauvais P.. Activation of alpha- and beta-estrogen receptors by persistent pesticides in reporter cell lines. Life Sci 79(12). 2006 Aug;1160−1169.
- 11. Wolff M.S., Toniolo P.G., Lee E.W.. Blood levels of organochlorine residues and risk of breast cancer. J Natl Cancer Inst 85(8). 1993 Apr;648−652.
- 12. Lopez-Cervantes M., Torres-Sanchez L., Tobias A.. Dichlorodiphenyldichloroethane burden and breast cancer risk: a meta-analysis of the epidemiologic evidence. Environ Health Perspect 112(2). 2004 Feb;207−214.
- 13. Laden F., Collman G., Iwamoto K.. 1,1-Dichloro-2,2-bis(p-chlorophenyl)ethylene and polychlorinated biphenyls and breast cancer: combined analysis of five U.S. studies. J Natl Cancer Inst 93(10). 2001 May;768−776.
- 14. Charlier C., Foidart J.M., Pitance F.. Environmental dichlorodiphenyltrichlorethane or hexachlorobenzene exposure and breast cancer: is there a risk? Clin Chem Lab Med 42(2). 2004 Feb;222−227.
- 15. Gammon M.D., Wolff M.S., Neugut A.I.. Environmental toxins and breast cancer on Long Island. II. Organochlorine compound levels in blood. Cancer Epidemiol Biomarkers Prev 11(8). 2002 Aug;686−697.
- 16. Ibarluzea J.J., Fernandez M.F., Santa-Marina L.. Breast cancer risk and the combined effect of environmental estrogens. Cancer Causes Control 15(6). 2004 Aug;591−600.
- 17. Iwasaki M., Inoue M., Sasazuki S.. Plasma organochlorine levels and subsequent risk of breast cancer among Japanese women: a nested case-control study. Sci Total Environ 402(2–3). 2008 Sep;176−183.
- 18. McCready D., Aronson K.J., Chu W.. Breast tissue organochlorine levels and metabolic genotypes in relation to breast cancer risk Canada. Cancer Causes Control 15(4). 2004 May;399−418.
- 19. Stroup D.F., Berlin J.A., Morton S.C.. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis of Observational Studies in Epidemiology (MOOSE) group. JAMA 283(15). 2000 Apr;2008−2012.
- 20. Higgins J.P., Thompson S.G.. Quantifying heterogeneity in a meta-analysis. Stat Med 21(11). 2002 Jun;1539−1558.
- 21. Olaya-Contreras P., Rodriguez-Villamil J., Posso-Valencia H.J.. Organochlorine exposure and breast cancer risk in Colombian women. Cad Saude Publica (14 Suppl 3). 1998;125−132.
- 22. Romieu I., Hernandez-Avila M., Lazcano-Ponce E.. Breast cancer, lactation history, and serum organochlorines. Am J Epidemiol 152(4). 2000;363−370.
- 23. Perera F.P., Rauh V., Whyatt R.M.. A summary of recent findings on birth outcomes and developmental effects of prenatal ETS, PAH, and pesticide exposures. Neurotoxicology 26(4). 2005 Aug;573−587.
- 24. Lopez-Carrillo L., Torres-Sanchez L., Moline J.. Breast-feeding and serum p,p'DDT levels among Mexican women of childbearing age: a pilot study. Environ Res 87(3). 2001 Dec;131−135.
- 25. Bradman A.S., Schwartz J.M., Fenster L.. Factors predicting organochlorine pesticide levels in pregnant Latina women living in a United States agricultural area. J Expos Sci Environ Epidemiol 17(4). 2007 Jul;388−399.
- 26. Aronson K.J., Miller A.B., Woolcott C.G.. Breast adipose tissue concentrations of polychlorinated biphenyls and other organochlorines and breast cancer risk. Cancer Epidemiol Biomarkers Prev 9(1). 2000 Jan;55−63.
- 27. Cohn B.A., Wolff M.S., Cirillo P.M.. DDT and breast cancer in young women: new data on the significance of age at exposure. Environ Health Perspect 115(10). 2007 Oct;1406−1414.
- 28. Dello Iacovo R., Celentano E., Strollo A.M.. Organochlorines and breast cancer. A study on Neapolitan women. Adv Exp Med Biol 472:1999;57−66.
- 29. Demers A., Ayotte P., Brisson J.. Risk and aggressiveness of breast cancer in relation to plasma organochlorine concentrations. Cancer Epidemiol Biomarkers Prev 9(2). 2000 Feb;161−166.
- 30. Dorgan J.F., Brock J.W., Rothman N.. Serum organochlorine pesticides and PCBs and breast cancer risk: results from a prospective analysis (USA). Cancer Causes Control 10(1). 1999 Feb;1−11.
- 31. Gatto N.M., Longnecker M.P., Press M.F.. Serum organochlorines and breast cancer: a case-control study among African-American women. Cancer Causes Control 18(1). 2007 Feb;29−39.
- 32. Helzlsouer K.J., Alberg A.J., Huang H.Y.. Serum concentrations of organochlorine compounds and the subsequent development of breast cancer. Cancer Epidemiol Biomarkers Prev 8(6). 1999 Jun;525−532.
- 33. Hoyer A.P., Grandjean P., Jorgensen T.. Organochlorine exposure and risk of breast cancer. Lancet 352(9143). 1998 Dec;1816−1820.
- 34. Hoyer A.P., Jorgensen T., Grandjean P.. Repeated measurements of organochlorine exposure and breast cancer risk (Denmark). Cancer Causes Control 11(2). 2000 Feb;177−184.
- 35. Itoh H., Iwasaki M., Hanaoka T.. Serum organochlorines and breast cancer risk in Japanese women: a case-control study. Cancer Causes Control 20(5). 2009 Jul;567−580.
- 36. Krieger N., Wolff M.S., Hiatt R.A.. Breast cancer and serum organochlorines: a prospective study among white, black, and Asian women. J Natl Cancer Inst 86(8). 1994 Apr;589−599.
- 37. Laden F., Hankinson S.E., Wolff M.S.. Plasma organochlorine levels and the risk of breast cancer: an extended follow-up in the Nurses' Health Study. Int J Cancer 91(4). 2001 Feb;568−574.
- 38. Liljegren G., Hardell L., Lindström G.. Case-control study on breast cancer and adipose tissue concentrations of congener specific polychlorinated biphenyls, DDE and hexachlorobenzene. Eur J Cancer Prev 7(2). 1998 Apr;135−140.
- 39. Lopez-Carrillo L., Blair A., Lopez-Cervantes M.. Dichlorodiphenyltrichloroethane serum levels and breast cancer risk: a case-control study from Mexico. Cancer Res 57(17). 1997 Sep;3728−3732.
- 40. Mendonca G.A., Eluf-Neto J., Andrada-Serpa M.J.. Organochlorines and breast cancer: a case–control study in Brazil. Int J Cancer 83(5). 1999 Nov;596−600.
- 41. Millikan R., DeVoto E., Duell E.J.. Dichlorodiphenyldichloroethene, polychlorinated biphenyls, and breast cancer among African-American and white women in North Carolina. Cancer Epidemiol Biomarkers Prev 9(11). 2000 Nov;1233−1240.
- 42. Moysich K.B., Ambrosone C.B., Vena J.E.. Environmental organochlorine exposure and postmenopausal breast cancer risk. Cancer Epidemiol Biomarkers Prev 7(3). 1998 Mar;181−188.
- 43. Pavuk M., Cerhan J.R., Lynch C.F.. Case-control study of PCBs, other organochlorines and breast cancer in Eastern Slovakia. J Expo Anal Environ Epidemiol 13(4). 2003 Jun;267−275.
- 44. Raaschou-Nielsen O., Pavuk M., Leblanc A.. Adipose organochlorine concentrations and risk of breast cancer among postmenopausal Danish women. Cancer Epidemiol Biomarkers Prev 14(1). 2005 Jan;67−74.
- 45. Rubin C.H., Lanier A., Kieszak S.. Breast cancer among Alaska Native women potentially exposed to environmental organochlorine chemicals. Int J Circumpolar Health 65:2006 Feb;18−27.
- 46. Schecter A., Toniolo P., Dai L.C.. Blood levels of DDT and breast cancer risk among women living in the North of Vietnam. Arch Environ Contam Toxicol 33(4). 1997 Nov;453−456.
- 47. Stellman S.D., Djordjevic M.V., Britton J.A.. Breast cancer risk in relation to adipose concentrations of organochlorine pesticides and polychlorinated biphenyls in Long Island, New York. Cancer Epidemiol Biomarkers Prev 9(11). 2000 Nov;1241−1249.
- 48. van't Veer P., Lobbezoo I.E., Martin-Moreno J.M.. DDT (dicophane) and postmenopausal breast cancer in Europe: case-control study. BMJ 315(7100). 1997 Jul;81−85.
- 49. Wolff M.S., Berkowitz G.S., Brower S.. Organochlorine exposures and breast cancer risk in New York City women. Environ Res 84(2). 2000 Oct;151−161.
- 50. Wolff M.S., Zeleniuch-Jacquotte A., Dubin N.. Risk of breast cancer and organochlorine exposure. Cancer Epidemiol Biomarkers Prev 9(3). 2000 Mar;271−277.
- 51. Zheng T., Holford T.R., Mayne S.T.. DDE and DDT in breast adipose tissue and risk of female breast cancer. Am J Epidemiol 150(5). 1999 Sep;453−458.
- 52. Zheng T., Holford T.R., Mayne S.T.. Risk of female breast cancer associated with serum polychlorinated biphenyls and 1,1-dichloro-2,2'-bis(p-chlorophenyl) ethylene. Cancer Epidemiol Biomarkers Prev 9(2). 2000 Feb;167−174.
Figure 1Process used for literature search.
Figure 2(A) Odds ratios (ORs) for DDT exposure and breast cancer. (B) Funnel plot of all included studies.
Figure 3(A) Odds ratios for DDT exposure and breast cancer in population-based case–control studies. (B) Funnel plot of population-based case–control studies.
Table 1Summary of papers included in the meta-analysis for DDT exposure and breast cancer risk
Table 1
| Author (year) |
Study years |
Country |
Design |
n (cases/controls) |
Biological specimen |
OR (95% CI) |
| Aronson (2000) [26]
|
1995–1997 |
Canada |
Hospital CC |
217/213 |
Adipose tissue |
1.10 (0.78–1.55) |
| Charlier (2004) [14]
|
2001–2002 |
Belgium |
Population CC |
231/290 |
Serum |
2.21 (1.41–3.48) |
| Cohn (2007) [27]
|
1959–1967 |
USA |
Hospital CC |
129/129 |
Serum |
1.29 (0.85–1.96) |
| Dello Lacovo (1999) [28]
|
1997–1998 |
Italy |
Population CC |
170/195 |
Serum |
1.02 (0.68–1.54) |
| Demers (2000) [29]
|
1994–1997 |
Canada |
Population CC |
315/307 |
Plasma |
0.91 (0.70–1.17) |
| Demers (2000) [29]
|
1994–1997 |
Canada |
Hospital CC |
315/219 |
Plasma |
1.01 (0.74–1.39) |
| Dorgan (1999) [30]
|
1977–1987 |
USA |
Nested CC |
105/207 |
Serum |
0.70 (0.47–0.99) |
| Gammon (2002) [15]
|
1996–1997 |
USA |
Population CC |
643/427 |
Serum |
1.20 (0.76–1.90) |
| Gatto (2007) [31]
|
1995–1998 |
USA |
Population CC |
355/327 |
Serum |
1.05 (0.82–1.35) |
| Helzlsouer (1999) [32]
|
1974 |
USA |
Nested CC |
235/235 |
Serum |
0.94 (0.71–1.25) |
| Helzlsouer (1999) [32]
|
1989 |
USA |
Nested CC |
105/105 |
Serum |
0.88 (0.56–1.38) |
| Hoyer (1998) [33]
|
1976 |
Denmark |
Nested CC |
237/469 |
Serum |
0.88 (0.56–1.37) |
| Hoyer (2000) [34]
|
1976–1978/1981–1983 |
Denmark |
Nested CC |
240/477 |
Serum |
1.04 (0.70–1.55) |
| Ibarluzea (2004) [16]
|
1996–1998 |
Spain |
Hospital CC |
198/260 |
Adipose tissue |
1.16 (0.83–1.62) |
| Itoh (2009) [35]
|
2001–2005 |
Japan |
Population CC |
349/349 |
Serum |
0.74 (0.48–1.13) |
| Iwasaki (2008) [17]
|
1990–1995 |
Japan |
Nested CC |
139/278 |
Plasma |
1.23 (0.80–1.90) |
| Krieger (1994) [36]
|
1964–1969 |
USA |
Nested CC |
150/150 |
Serum |
1.31 (0.82–2.09) |
| Laden (2001) [37]
|
1989–1990 |
USA |
Nested CC |
372/372 |
Plasma |
0.79 (0.61–1.01) |
| Liljegren (1998) [38]
|
1993–1995 |
Sweden |
Hospital CC |
43/35 |
Adipose tissue |
0.40 (0.10–1.20) |
| Lopez-Carrillo (1997) [39]
|
1994–1996 |
Mexico |
Hospital CC |
141/141 |
Serum |
0.68 (0.43–1.07) |
| McCready (2004) [18]
|
1995–1997 |
Canada |
Hospital CC |
68/52 |
Adipose tissue |
2.48 (1.08–5.71) |
| Mendonca (1999) [40]
|
1995–1996 |
Brazil |
Hospital CC |
162/331 |
Serum |
1.05 (0.75–1.46) |
| Millikan (2000) [41]
|
1993–1996 |
USA |
Population CC |
748/659 |
Plasma |
1.07 (0.86–1.32) |
| Moysich (1998) [42]
|
1986–1991 |
USA |
Population CC |
154/192 |
Serum |
1.15 (0.74–1.79) |
| Olaya-Contreras (1998) [21]
|
1995–1996 |
Colombia |
Hospital CC |
153/153 |
Serum |
1.56 (1.02–2.39) |
| Pavuk (2003) [43]
|
1997–1999 |
USA |
Hospital CC |
24/85 |
Serum |
1.49 (0.45–4.87) |
| Raaschou-Nielsen (2005) [44]
|
1993–1997 |
Denmark |
Nested CC |
363/363 |
Adipose tissue |
0.87 (0.69–1.10) |
| Romieu (2000) [22]
|
1990–1995 |
Mexico |
Population CC |
120/126 |
Serum |
2.02 (1.14–3.57) |
| Rubin (2005) [45]
|
1981–1987 |
USA |
Population CC |
63/63 |
Serum |
0.97 (0.41–2.32) |
| Schecter (1997) [46]
|
1994 |
Vietnam |
Hospital CC |
21/21 |
Serum |
0.69 (0.23–2.07) |
| Stellman (2000) [47]
|
1994–1996 |
USA |
Hospital CC |
232/323 |
Adipose tissue |
0.94 (0.66–1.33) |
| van't Veer (1997) [48]
|
1991–1992 |
Five European countries |
Hospital CC |
265/341 |
Adipose tissue |
0.75 (0.52–1.08) |
| Wolff (1993) [11]
|
1985–1991 |
USA |
Population CC |
58/171 |
Serum |
2.30 (1.31–4.04) |
| Wolff (2000) [49]
|
1994–1996 |
USA |
Hospital CC |
151/317 |
Serum |
0.86 (0.61–1.22) |
| Wolff (2000) [50]
|
1987–1992 |
USA |
Nested CC |
110/213 |
Serum |
0.83 (0.50–1.37) |
| Zheng (1999) [51]
|
1994–1997 |
USA |
Hospital CC |
304/304 |
Adipose tissue |
1.02 (0.73–1.41) |
| Zheng (2000) [52]
|
1995–1997 |
USA |
Hospital CC |
475/502 |
Serum |
1.01 (0.79–1.28) |
Table 2Meta-analysis of the effect of the exposure to DDT on the risk of breast cancer according to subgroup
Table 2
| Studies included |
No. of Studies |
OR |
95% CI |
Heterogeneity
|
Egger’s test (p for bias) |
|
p-value |
I2 (%) |
| Type of study design |
| Hospital CC |
16 |
1.02 |
0.91 to 1.15 |
0.183 |
24.0 |
0.780 |
| Population CC |
11 |
1.19 |
0.99 to 1.44 |
0.004 |
61.3 |
0.212 |
| Nested CC |
10 |
0.90 |
0.81 to 1.01 |
0.554 |
0.0 |
0.274 |
| Study years |
| 2000s |
2 |
1.28 |
0.44 to 3.71 |
0.001 |
91.5 |
– |
| 1990s |
27 |
1.03 |
0.94 to 1.24 |
0.034 |
35.9 |
0.169 |
| 1980s |
4 |
0.87 |
0.69 to 1.09 |
0.575 |
0.0 |
0.908 |
| 1970s |
2 |
0.92 |
0.73 to 1.17 |
0.808 |
0.0 |
– |
| 1960s |
2 |
1.30 |
0.95 to 1.77 |
0.962 |
0.0 |
– |
| Type of biologic specimen |
| Serum |
24 |
1.07 |
0.93 to 1.11 |
0.006 |
47.0 |
0.365 |
| Plasma |
5 |
0.97 |
0.85 to 1.11 |
0.325 |
14.1 |
0.910 |
| Adipose tissue |
8 |
0.98 |
0.83 to 1.16 |
0.141 |
36.0 |
0.228 |
| Country |
| North America |
22 |
1.01 |
0.92 to 1.10 |
0.185 |
21.0 |
0.524 |
| Europe |
8 |
1.02 |
0.81 to 1.29 |
0.010 |
62.0 |
0.246 |
| Asia |
3 |
0.92 |
0.63 to 1.36 |
0.226 |
32.8 |
0.900 |
| South America |
4 |
1.20 |
0.78 to 1.83 |
0.012 |
72.8 |
0.707 |
Citations
Citations to this article as recorded by
- Bisphenol A and DDT disrupt adipocyte function in the mammary gland: implications for breast cancer risk and progression
Sarah M. Bernhardt, Carrie D. House
Frontiers in Oncology.2025;[Epub] CrossRef - Biological concentrations of DDT metabolites and breast cancer risk: an updated systematic review and meta-analysis
Rodrigo Ugalde-Resano, Brenda Gamboa-Loira, Ángel Mérida-Ortega, Alma Rincón-Rubio, Gisela Flores-Collado, Maricela Piña-Pozas, Lizbeth López-Carrillo
Reviews on Environmental Health.2025; 40(1): 225. CrossRef - Breast adipose tissue level of organochlorine pesticides as a risk factor in breast cancer: A cross sectional study in North Indian females
Krishna Latha Thammineni, Gaurav K. Thakur, Basu Dev Banerjee, Navneet Kaur
Chemosphere.2025; 377: 144339. CrossRef - Endocrine disrupting chemicals exposure and health: An umbrella review
Junhao Chen, Pan Song, Chao Li, Hengjia Liu, Lei Zhang, Yi Zhou, Zhien Zhou, Weigang Yan
Ecotoxicology and Environmental Safety.2025; 302: 118574. CrossRef - Risk factors for breast cancer: an umbrella review of observational cohort studies and causal relationship analysis
Zhuo Wang, Lei Feng, Yuqing Xia, Zheming Zhu, Lina Wu, Song Gao
Frontiers in Oncology.2025;[Epub] CrossRef - Isolation and Characterization of Propoxur-Degrading Bacteria, Brucella pseudintermedia LED 6 from a Pineapple Plantation in Lampung
Taufiq Hidayat, Rahayu Widyastuti, Gunawan Djajakirana, Sarjiya Antonius, Tirta Kumala Dewi
Jurnal Ilmu Pertanian Indonesia.2025; 30(4): 725. CrossRef - Mapping meta-analyses on organochlorine pesticides reveals low methodological quality
Kyle Morrison, Yefeng Yang, Coralie Williams, Lorenzo Ricolfi, Malgorzata Lagisz, Shinichi Nakagawa
Nature Sustainability.2025;[Epub] CrossRef - Causes and Risk Factors of Breast Cancer, What Do We Know for Sure? An Evidence Synthesis of Systematic Reviews and Meta-Analyses
Borghild Løyland, Ida Hellum Sandbekken, Ellen Karine Grov, Inger Utne
Cancers.2024; 16(8): 1583. CrossRef - Breast cancer immunophenotypes and serum organochlorine pesticides in Mexican women: Mixture exposure approach
Rodrigo Ugalde-Resano, Ángel Mérida-Ortega, Mariano E. Cebrián, Lizbeth López-Carrillo
Environmental Pollution.2024; 358: 124495. CrossRef - Non-genetic factors and breast cancer: an umbrella review of meta-analyses
Anneza Yiallourou, Katerina Pantavou, Georgios Markozannes, Antonis Pilavas, Andrea Georgiou, Andria Hadjikou, Mary Economou, Neophytos Christodoulou, Konstantinos Letsos, Elina Khattab, Chrystalleni Kossyva, Maria Constantinou, Melanie Theodoridou, Danie
BMC Cancer.2024;[Epub] CrossRef - Validation and green profile assessment of a binary solvent liquid phase microextraction method for the determination of chlorbenside and fenobucarb in lake and wastewater samples by GC–MS
Dotse Selali Chormey
Environmental Science and Pollution Research.2023; 30(15): 44697. CrossRef - Putative interactions between transthyretin and endosulfan II and its relevance in breast cancer
Saurabh Sharma, Lakshay Malhotra, Paromita Mukherjee, Navneet Kaur, Thammineni Krishanlata, Chittur V. Srikanth, Vandana Mishra, Basu Dev Banerjee, Abdul Samath Ethayathulla, Radhey Shyam Sharma
International Journal of Biological Macromolecules.2023; 235: 123670. CrossRef - Exposure to Organochlorine Pesticides and Female Breast Cancer Risk According to Molecular Receptors Expression: a Systematic Review and Meta-analysis of Epidemiological Evidence
Rodrigo Ugalde-Resano, Brenda Gamboa-Loira, Ángel Mérida-Ortega, Alma Rincón-Rubio, Gisela Flores-Collado, Maricela Piña-Pozas, Lizbeth López-Carrillo
Current Environmental Health Reports.2023; 10(4): 442. CrossRef - Mosquito control exposures and breast cancer risk: analysis of 1071 cases and 2096 controls from the Ghana Breast Health Study
Naomie Olivos, Jim E. Banta, Rhonda Spencer-Hwang, Daniel Ansong, Laura E. Beane Freeman, Joe-Nat Clegg-Lamptey, Beatrice Wiafe-Addai, Lawrence Edusei, Ernest Adjei, Nicholas Titiloye, Florence Dedey, Francis Aitpillah, Joseph Oppong, Verna Vanderpuye, Er
Breast Cancer Research.2023;[Epub] CrossRef - Endocrine disrupting chemicals and breast cancer: a systematic review of epidemiological studies
Murphy Lam Yim Wan, Vanessa Anna Co, Hani El-Nezami
Critical Reviews in Food Science and Nutrition.2022; 62(24): 6549. CrossRef - Epidemiology beyond its limits
Lauren E. McCullough, Maret L. Maliniak, Avnika B. Amin, Julia M. Baker, Davit Baliashvili, Julie Barberio, Chloe M. Barrera, Carolyn A. Brown, Lindsay J. Collin, Alexa A. Freedman, David C. Gibbs, Maryam B. Haddad, Eric W. Hall, Sarah Hamid, Kristin R. V
Science Advances.2022;[Epub] CrossRef - Plasma concentrations of chlorinated persistent organic pollutants and their predictors in the general population of Algiers, Algeria
El Hadia Mansouri, Mohamed Reggabi
Emerging Contaminants.2021; 7: 35. CrossRef - Association between type 2 diabetes and exposure to chlorinated persistent organic pollutants in Algeria: A case-control study
El Hadia Mansouri, Mohamed Reggabi
Chemosphere.2021; 264: 128596. CrossRef - Extraction of Chlorobenzenes and PCBs from Water by ZnO Nanoparticles
Yuntao Zhang, Ran Chen, Jim E. Riviere, Jeffrey Comer
Processes.2021; 9(10): 1764. CrossRef - Two Cases of Possible Familial Chronic Myeloid Leukemia in a Family with Extensive History of Cancer
Marisa J.L. Aitken, Christopher B. Benton, Ghayas C. Issa, Koji Sasaki, Musa Yilmaz, Nicholas J. Short
Acta Haematologica.2021; 144(5): 585. CrossRef - In utero DDT exposure and breast density before age 50
Nickilou Y. Krigbaum, Piera M. Cirillo, Julie D. Flom, Jasmine A. McDonald, Mary Beth Terry, Barbara A. Cohn
Reproductive Toxicology.2020; 92: 85. CrossRef - DDT exposure during pregnancy and DNA methylation alterations in female offspring in the Child Health and Development Study
Hui-Chen Wu, Barbara A. Cohn, Piera M. Cirillo, Regina M. Santella, Mary Beth Terry
Reproductive Toxicology.2020; 92: 138. CrossRef - Prediagnostic serum concentrations of organochlorine pesticides and non-Hodgkin lymphoma: A nested case–control study in the Norwegian Janus Serum Bank Cohort
Dazhe Chen, Tom K. Grimsrud, Hilde Langseth, Dana B. Barr, Bryan A. Bassig, Aaron Blair, Kenneth P. Cantor, Marilie D. Gammon, Qing Lan, Nathaniel Rothman, Lawrence S. Engel
Environmental Research.2020; 187: 109515. CrossRef - Global trends in pesticides: A looming threat and viable alternatives
Akanksha Sharma, Ananya Shukla, Kriti Attri, Megha Kumar, Puneet Kumar, Ashish Suttee, Gurpal Singh, Ravi Pratap Barnwal, Neha Singla
Ecotoxicology and Environmental Safety.2020; 201: 110812. CrossRef - Exposure to Endocrine Disrupting Chemicals and Risk of Breast Cancer
Louisane Eve, Béatrice Fervers, Muriel Le Romancer, Nelly Etienne-Selloum
International Journal of Molecular Sciences.2020; 21(23): 9139. CrossRef - Breast Cancer and Exposure to Organochlorines in the CECILE Study: Associations with Plasma Levels Measured at the Time of Diagnosis and Estimated during Adolescence
Delphine Bachelet, Marc-André Verner, Monica Neri, Émilie Cordina Duverger, Corinne Charlier, Patrick Arveux, Sami Haddad, Pascal Guénel
International Journal of Environmental Research an.2019; 16(2): 271. CrossRef - Risk of breast cancer and adipose tissue concentrations of polychlorinated biphenyls and organochlorine pesticides: a hospital-based case-control study in Chinese women
Wenlong Huang, Yuanfang He, Jiefeng Xiao, Yuanni Huang, Anna Li, Meirong He, Kusheng Wu
Environmental Science and Pollution Research.2019; 26(31): 32128. CrossRef - Serum levels of Organochlorine Pesticides and Breast Cancer Risk in Iranian Women
Parisa Paydar, Gholamreza Asadikaram, Hossein Fallah, Hamid Zeynali Nejad, Hamed Akbari, Moslem Abolhassani, Vahid Moazed, Payam Khazaeli, Mahmoud Reza Heidari
Archives of Environmental Contamination and Toxico.2019; 77(4): 480. CrossRef - DDT exposure in early childhood and female breast cancer: Evidence from an ecological study in Taiwan
Simon Chang, Sonia El-Zaemey, Jane Heyworth, Meng-chi Tang
Environment International.2018; 121: 1106. CrossRef - Chiral pharmaceuticals: Environment sources, potential human health impacts, remediation technologies and future perspective
Yaoyu Zhou, Shikang Wu, Hao Zhou, Hongli Huang, Jia Zhao, Yaocheng Deng, Hua Wang, Yuan Yang, Jian Yang, Lin Luo
Environment International.2018; 121: 523. CrossRef - Organochlorine pesticides accumulation and breast cancer: A hospital-based case–control study
Ting-Ting He, An-Jun Zuo, Ji-Gang Wang, Peng Zhao
Tumor Biology.2017; 39(5): 101042831769911. CrossRef - Correlation between toxic organochlorine pesticides and breast cancer
SA Eldakroory, DA El Morsi, RH Abdel-Rahman, S Roshdy, MS Gouida, EO Khashaba
Human & Experimental Toxicology.2017; 36(12): 1326. CrossRef - Breast cancer and persistent organic pollutants (excluding DDT): a systematic literature review
Tafzila Akter Mouly, Leisa-Maree Leontjew Toms
Environmental Science and Pollution Research.2016; 23(22): 22385. CrossRef
