1,1-Dichloro-2,2-bis(p-chlorophenyl)ethylene and polychlorinated biphenyls and breast cancer: combined analysis of five U.S. studies.
BACKGROUND
Environmental exposure to organochlorines has been examined as a potential risk factor for breast cancer. In 1993, five large U.S. studies of women located mainly in the northeastern United States were funded to evaluate the association of levels of 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (DDE) and polychlorinated biphenyls (PCBs) in blood plasma or serum with breast cancer risk. We present a combined analysis of these results to increase precision and to maximize statistical power to detect effect modification by other breast cancer risk factors.


METHODS
We reanalyzed the data from these five studies, consisting of 1400 case patients with breast cancer and 1642 control subjects, by use of a standardized approach to control for confounding and assess effect modification. We calculated pooled odds ratios (ORs) and 95% confidence intervals (CIs) by use of the random-effects model. All statistical tests were two-sided.


RESULTS
When we compared women in the fifth quintile of lipid-adjusted values with those in the first quintile, the multivariate pooled OR for breast cancer associated with PCBs was 0.94 (95% CI = 0.73 to 1.21), and that associated with DDE was 0.99 (95% CI = 0.77 to 1.27). Although in the original studies there were suggestions of elevated breast cancer risk associated with PCBs in certain groups of women stratified by parity and lactation, these observations were not evident in the pooled analysis. No statistically significant associations were observed in any other stratified analyses, except for an increased risk with higher levels of PCBs among women in the middle tertile of body mass index (25-29.9 kg/m(2)); however, the risk was statistically nonsignificantly decreased among heavier women.


CONCLUSIONS
Combined evidence does not support an association of breast cancer risk with plasma/serum concentrations of PCBs or DDE. Exposure to these compounds, as measured in adult women, is unlikely to explain the high rates of breast cancer experienced in the northeastern United States.
Laden
F
F
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. francine.laden@channing.harvard.edu
Collman
G
G
Iwamoto
K
K
Alberg
A J
AJ
Berkowitz
G S
GS
Freudenheim
J L
JL
Hankinson
S E
SE
Helzlsouer
K J
KJ
Holford
T R
TR
Huang
H Y
HY
Moysich
K B
KB
Tessari
J D
JD
Wolff
M S
MS
Zheng
T
T
Hunter
D J
DJ
D001835:Body Weight; D001943:Breast Neoplasms / Q000139:chemically induced* / Q000209:etiology*; D016022:Case-Control Studies; D003633:Dichlorodiphenyl Dichloroethylene / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000097:blood; D004785:Environmental Pollutants / Q000009:adverse effects / Q000097:blood; D005260:Female; D006801:Humans; D015233:Models, Statistical; D015337:Multicenter Studies as Topic; D016017:Odds Ratio; D011078:Polychlorinated Biphenyls / Q000009:adverse effects* / Q000097:blood; D012307:Risk Factors
D004785:Environmental Pollutants; D003633:Dichlorodiphenyl Dichloroethylene; D011078:Polychlorinated Biphenyls