Evidence From Humans
 
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Breast tissue organochlorine levels and metabolic genotypes in relation to breast cancer risk Canada
McCready, D., Aronson, K. J., Chu, W., Fan, W., Vesprini, D., Narod, S. A. Cancer Causes and Control. 2004. 15:4, 399-418.
Topic area
Environmental pollutant - Pesticide, organochlorine, PCB, DDE, DDT, cis-nona
Study design
Hospital based case-control
Funding agency
Other: Canadian Breast Cancer Foundation Other: Ca
Study Participants
Menopausal Status
The menopausal status of women included in this study is listed here.
Pre menopausal
Post menopausal
Number of Controls
Controls: 69
Participant selection: Inclusion and exclusion criteria
Criteria used to select participants in the study.
Women were recruited if they were scheduled for an excision biopsy at a Toronto hospital between July 1995 and June 1997. Cases were women diagnosed with invasive breast cancer. Controls were women diagnosed with benign breast disease.
Exposures investigated
Lipid adjusted concentrations of organochlorines in non-cancerous breast tissue, CYP1A1, CYP1A2, CYP3A4, GSTM1, GSTT1 polymorphisms
Statistical Analysis
Ethnic groups with separate analysis
If this study provided a separate analysis by ethnic or racial group, the groups are listed here.
No
Confounders considered
Other breast cancer risk factors, such as family history, age at first birth, and hormone replacement therapy use, that were taken into account in the study.
Age, menopausal status, lactation, BMI, smoking, alcohol, and fat consumption.
Genetic characterization included
If the study analyzed relationships between environmental factors and inherited genetic variations, this field will be marked “Yes.” “No”, if not.
Yes
Description of major analysis
Logistic regression was used to calculate odds-ratios for organochlorines and breast cancer risk, genotype and breast cancer risk, and organochlorines and breast cancer risk as modified by genotype.
Strength of associations reported
Increased breast cancer risks were seen for:
PCB 99 (OR = 2.4, 95% CI: 0.95-6.04)
PCB 105 (OR = 2.5, 95% CI: 1.02-6.13)
p,p'-DDE (OR = 2.48, 95% CI: 1.08-5.71)
p,p'-DDT (OR = 2.33, 95% CI: 0.97-5.61).

Among the genetic polymorphisms, increased risk was seen for the null deletion of GSTM1 (OR = 2.2, 95% CI: 1.09-4.42), and GSTT1 (OR = 1.59, 95% CI: 0.63-4.04). Reduced risks were seen most strongly in the CYP1A1-M2 variant (OR = 0.26, 95% CI: 0.07-1.01), but also for the CYP1A1-M4, CYP1A1-M1, CYP1A2, and CYP3A4 variants (ORs = 0.64, 0.65, 0.66, and 0.74, respectively).

However, when the association between the CYP1A1 polymorphism and breast cancer risk is stratified by PCB level, the variant is still primarily associated with decreased breast cancer risk among women with low PCB burden, but is associated with increased risk among women with high PCB levels.

The breast cancer odds-ratios for organochlorine exposure were generally higher among women with the GSTM1 null variant (18 of 19 organochlorines). However, the only risk which was significantly different from 1 was for p,p'-DDT among the GSTM1 null group (OR = 3.7, 95% CI: 1.1-12.41). The interaction p-values were significant for Oxychlordane (OR for increased exposure = 0.38 for homozygous or heterozygous wild-type, but 2.3 for the null variant), HCB (OR for increased exposure = 0.46 for homozygous or heterozygous wild-type, but 2.85 for the null variant), and beta-HCH (OR for increased exposure = 0.21 for homozygous or heterozygous wild-type, but 1.35 for the null variant).

Conversely, the breast cancer odds-ratios for organochlorine exposure were generally lower among women with the CYP1A1-M1 variants (17 of 19 organochlorines). The interaction p-values were significant for PCB 180 (OR for increased exposure = 1.05 for homozygous wild-type, but 0.06 for the variant) and PCB 187 (OR for increased exposure = 1.75 for homozygous wild-type, but 0.12 for the variant).
Results Comments
Although many comparisons were made and the systems are complex, the data as a whole were suggestive of a gene/environment interaction. For a substantial number of organochlorines, the association with breast cancer risk changed directions between different alleles of a given gene.
Author address
Department of Surgery, University Health Network, Toronto, Ontario, Canada.
Reviewers Comments
Enzyme activity levels were not measured, just genetic sequences, even though the former may be of greater functional interest. Activity levels are affected both by the enzyme kinetics, and by the enzyme concentration. Although the enzyme kinetics are primarily a function of the genetic sequence, the enzyme concentration depends on the induction rates, which can be affected both by genetics and by the presence of environmental inducers.
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