Serum concentrations of 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) and risk of primary liver cancer.
BACKGROUND
1,1,1-Trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) exposure has been demonstrated to cause liver tumors in laboratory rodents. DDT's persistent metabolite and environmental degradation product, 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE), has also been associated with liver tumors in laboratory animals. Whether DDT and DDE are associated with hepatocarcinogenesis in humans is not clear.


METHODS
We carried out a nested case-control study among the participants of the Nutritional Intervention Trials in Linxian, China. The case group included 168 individuals who developed liver cancer during the trials, and the control group included 385 individuals frequency-matched on age and sex who were alive and well at the end of the study. Serum concentrations of DDT and DDE were measured by gas chromatography-mass spectrometry. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariable analysis.


RESULTS
In multivariable-adjusted models, the risk of developing liver cancer increased with increased serum DDT concentration (OR for quintile 1 versus quintile 5 = 3.8, 95% CI = 1.7 to 8.6, P(trend) = .0024). In contrast, there was no statistically significant association between liver cancer and serum DDE concentration. The association between high serum DDT concentration and liver cancer was stronger among individuals with DDE concentrations below the median value (odds ratio for tertile 3 versus tertile 1 = 3.55, 95% CI = 1.45 to 8.74) than those with concentrations above the median (OR = 1.70, 95% CI = 0.97 to 2.98). A calculation of crude liver cancer risk found that there would be 26 liver cancers per 100 000 persons per year in the lowest quintile of DDT exposure versus 46 liver cancers per 100 000 persons per year in the highest quintile of DDT exposure.


CONCLUSIONS
DDT may be a risk factor for liver cancer, particularly among persons with lower DDE concentrations. Risk may be particularly increased among persons exposed directly to DDT (resulting in a higher ratio of DDT to DDE) or, alternatively, risk may be associated with individual ability to metabolize DDT to DDE.
McGlynn
Katherine A
KA
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, EPS-7060, 6120 Executive Blvd., Rockville, MD 20852-7234, USA. mcglynnk@mail.nih.gov
Abnet
Christian C
CC
Zhang
Mingdong
M
Sun
Xiu-Di
XD
Fan
Jin-Hu
JH
O'Brien
Thomas R
TR
Wei
Wen-Qiang
WQ
Ortiz-Conde
Betty A
BA
Dawsey
Sanford M
SM
Weber
Jean-Philippe
JP
Taylor
Philip R
PR
Katki
Hormuzd
H
Mark
Steven D
SD
Qiao
You-Lin
YL
D000328:Adult; D000368:Aged; D002273:Carcinogens; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D003634:DDT / Q000009:adverse effects* / Q000097:blood; D003633:Dichlorodiphenyl Dichloroethylene / Q000009:adverse effects* / Q000097:blood; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D006801:Humans; D016014:Linear Models; D008113:Liver Neoplasms / Q000097:blood / Q000139:chemically induced* / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D018570:Risk Assessment; D012307:Risk Factors
D002273:Carcinogens; D003633:Dichlorodiphenyl Dichloroethylene; D003634:DDT