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Breast tissue organochlorine levels and metabolic genotypes in relation to breast cancer risk Canada.

https://arctichealth.org/en/permalink/ahliterature180138
Source
Cancer Causes Control. 2004 May;15(4):399-418
Publication Type
Article
Date
May-2004
Author
David McCready
Kristan J Aronson
William Chu
Wenli Fan
Danny Vesprini
Steven A Narod
Author Affiliation
Department of Surgery, University Health Network, Toronto, Ontario, Canada.
Source
Cancer Causes Control. 2004 May;15(4):399-418
Date
May-2004
Language
English
Publication Type
Article
Keywords
Adult
Aged
Alleles
Breast - chemistry
Breast Neoplasms - chemically induced - etiology - genetics
Carcinogens - adverse effects - metabolism
Case-Control Studies
Confidence Intervals
Environmental Exposure - adverse effects
Environmental Pollutants - adverse effects
Female
Genetic Variation
Genotype
Glutathione Transferase - genetics - metabolism
Humans
Hydrocarbons, Chlorinated
Insecticides - adverse effects - metabolism
Middle Aged
Odds Ratio
Ontario - epidemiology
Risk assessment
Risk factors
Abstract
Genes that metabolize the rate of clearance of environmental carcinogens may be candidate genes for cancer susceptibility. There is some data to suggest that exposure to environmental pesticides and other organochlorine pollutants is a risk factor to breast cancer. It is therefore reasonable to ask if variants in the genes responsible for the metabolic activation of organochlorines are associated with different tissue burdens of organochlorines and if these variants modify the risk of breast cancer in the population. We conducted a case-control study of women who underwent an excision biopsy for suspected breast cancer in a Toronto hospital from 1995 to 1997. Patients are residents of the Greater Toronto Area and are primarily Caucasian of European descent. Cases were women with invasive breast cancer (n = 70) and controls (n = 69) were women diagnosed with benign disease, frequency matched by age to cases. Levels of organochlorines were measured in benign breast tissue and seven polymorphisms in five candidate genes were genotyped. In general, women who carried inactive alleles of the GSTM1 had higher levels of breast organochlorines, and were at modestly increased risk of breast cancer (odds ratio = 2.2; 95% CI = 1.1-4.4). However, multiple comparisons were made and generally our data do not support the hypothesis that organochlorines increase the risk of breast cancer among subgroups of women with specific metabolic genotypes.
PubMed ID
15141140 View in PubMed
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The N314D polymorphism of galactose-1-phosphate uridyl transferase does not modify the risk of ovarian cancer.

https://arctichealth.org/en/permalink/ahliterature184439
Source
Cancer Epidemiol Biomarkers Prev. 2003 Jul;12(7):678-80
Publication Type
Article
Date
Jul-2003
Author
W L Alan Fung
Harvey Risch
John McLaughlin
Barry Rosen
David Cole
Danny Vesprini
Steven A Narod
Author Affiliation
The Center for Research in Women's Health, University of Toronto, Toronto, Ontario, M5G 1N8 Canada.
Source
Cancer Epidemiol Biomarkers Prev. 2003 Jul;12(7):678-80
Date
Jul-2003
Language
English
Publication Type
Article
Keywords
Adult
Aged
Aged, 80 and over
Canada - epidemiology
Case-Control Studies
Female
Galactose - metabolism
Genotype
Humans
Middle Aged
Ovarian Neoplasms - epidemiology - genetics
Polymorphism, Genetic
UTP-Hexose-1-Phosphate Uridylyltransferase - genetics - metabolism
Abstract
It has been proposed that high levels of galactose consumption increase the risk of ovarian cancer. Galactose levels are determined, in part, by the galactose-1-phosphate uridyl transferase gene (GALT). The N314D allele of the GALT gene has been associated with low GALT activity and with an increased risk of ovarian cancer. We screened for the presence of the N314D GALT allele in 891 incident cases of epithelial ovarian cancer and in 364 unaffected female controls. No significant difference in the prevalence of the N314D allele was observed between the cases (18.1%) and the controls (18.7%). The odds ratio associated with the presence of one N314D allele was 0.94 (95% confidence interval (CI), 0.68-1.3; P = 0.70), and the odds ratio associated with two N314D alleles was 1.62 (95% CI, 0.34-7.7; P = 0.54). Subanalyses of the cases by histological type, by age, by ethnic group, by family history, and by BRCA1/2 mutation status did not reveal any significant associations. We conclude that the GALT N314D allele does not predispose to epithelial ovarian cancer.
PubMed ID
12869412 View in PubMed
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A polymorphic locus in the promoter region of the IGFBP3 gene is related to mammographic breast density.

https://arctichealth.org/en/permalink/ahliterature180731
Source
Cancer Epidemiol Biomarkers Prev. 2004 Apr;13(4):573-82
Publication Type
Article
Date
Apr-2004
Author
Joe H Lai
Danny Vesprini
William Zhang
Martin J Yaffe
Michael Pollak
Steven A Narod
Author Affiliation
Centre for Research in Women's Health, University of Toronto, 8790 Bay Street, Toronto, Ontario, M5G 1N8 Canada.
Source
Cancer Epidemiol Biomarkers Prev. 2004 Apr;13(4):573-82
Date
Apr-2004
Language
English
Publication Type
Article
Keywords
Adult
Aged
Aged, 80 and over
Breast Neoplasms - blood - radiography
Female
Humans
Insulin-Like Growth Factor Binding Protein 3 - blood
Insulin-Like Growth Factor I - metabolism
Mammography
Middle Aged
Ontario - epidemiology
Polymorphism, Genetic
Predictive value of tests
Tumor Markers, Biological - blood
Abstract
Mammographic breast density is a significant risk factor for breast cancer. Women with dense tissue accounting for more than 60-75% of the area of the breast have a 4- to 6-fold increase in their risk of breast cancer, compared to women with little or no breast density. A high circulating level of insulin-like growth factor-I (IGF-I) and low IGF binding protein 3 (IGFBP-3) level have been associated with increased breast density in premenopausal women. Genetic polymorphisms in the IGF1 and IGFBP3 genes may influence breast and serum levels of these growth factors. The aims of this study were to determine whether polymorphic variations in the IGF1 and IGFBP3 genes are associated with breast density, and serum IGF-I and IGFBP-3 levels, and whether serum IGF-I and IGFBP-3 levels are associated with mammographic density.
A total of 441 white women, recruited from Women's College Hospital (Toronto, Ontario), enrolled in this study. Each woman completed a questionnaire, detailing information on age, menstrual history, hormone use, diet, and medical and mammography history. Blood samples were taken for DNA extraction to genotype the subjects for polymorphic variants in the two candidate genes, and for measurement of circulating levels of IGF-I and IGFBP-3. Mammographic films were retrieved from Women's College Hospital and digitized using a laser film scanner. The digitized images were assessed for breast density using a computer-assisted method.
There was a positive association between serum IGFBP-3 levels and the number of A alleles at a previously described polymorphic locus in the promoter region of the IGFBP3 gene among premenopausal women (P = 0.01). There was also a positive trend in the mean percentage of breast density by the number of A alleles of the IGFBP3 gene among premenopausal women (P = 0.0005). Women with two A alleles had a 5-fold increase in the odds of having a percentage of breast density greater or equal to 28%, compared with women with no A allele (P = 0.002). However, there was no association between serum IGF-I and IGFBP-3 levels and breast density among premenopausal women (P > 0.05).
This is the first study to report a strong relationship between a polymorphic gene locus (IGFBP3) and mammographic breast density. However, we could not confirm an association between serum IGF-I levels and breast density among premenopausal women, as demonstrated in previous studies.
PubMed ID
15066922 View in PubMed
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