| Polymorphisms in DNA repair genes, ionizing radiation exposure and risk of breast cancer in U.S. radiologic technologists
(2008
) |
| | We investigated the potential modification of radiation-related breast cancer risk by 55 candidate single nucleotide polymorphisms in 17 genes involved in base excision or DNA double-strand break repair among 859 cases and 1083 controls. A variant in the WRN gene significantly modified the association between occupational breast dose and breast cancer risk, while one variant in the BRCA1 gene and three variants in the PRKDC gene significantly altered the personal diagnostic radiation exposure-response relationship.
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| | [Abstract] [PubMed] |
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| A common coding variant in CASP8 is associated with breast cancer risk
(2007
) |
| | The Breast Cancer Association Consortium (BCAC), which includes the U.S. Radiologic Technologist Study, was established to conduct combined case-control studies to confirm genetic associations with breast cancer. Nine single-nucleotide polymorphisms that were previously associated with breast cancer were studied. BCAC found evidence of an association with a common coding variant in the CASP8 gene.
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| | [Abstract] [PubMed] |
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| Genome-wide association study identifies multiple novel breast cancer susceptibility loci
(2007
) |
| | The Breast Cancer Association Consortium (BCAC), which includes the U.S. Radiologic Technologist Study, was established to conduct combined case-control studies to confirm genetic associations with breast cancer. To identify additional breast cancer susceptibility alleles, BCAC conducted a two-stage genome-wide association study, followed by a third stage in which 30 single-nucleotide polymorphisms were tested for confirmation in cases and controls from 22 studies.
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| | [Abstract] [PubMed] |
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| Polymorphisms in apoptosis- and proliferation-related genes, ionizing radiation exposure, and risk of breast cancer among U.S. radiologic technologists
(2007
) |
| | In a case-control study of 859 breast cancer cases and 1083 controls, we assessed breast cancer risk related to 16 candidate variants in eight genes involved in apoptosis, inflammation, and proliferation, and the joint effects of these variants with occupational and personal diagnostic radiation on risk. We found that IL1A A114S significantly modified the radiation dose-response relationship between cumulative personal diagnostic radiation and breast cancer risk, adjusted for occupational radiation dose.
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| | [Abstract] [PubMed] |
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| Commonly studied single-nucleotide polymorphisms and breast cancer: results from the Breast Cancer Consortium
(2006
) |
| | Large sample sizes are needed to detect and confirm, at appropriate levels of statistical significance, genetic variants that are associated with modest increases in cancer risk. We participate in the Breast Cancer Association Consortium, which includes more than 20 international collaborative groups, with a combined sample size in excess of 30,000 breast cancer cases and 30,000 controls. The current study evaluated 16 single-nucleotide polymorphisms that were previously evaluated by at least 3 of the participating centers. Five of the SNPs were found to be associated with breast cancer risk, while 11 were not.
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| | [Abstract] [PubMed] |
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| The ATM missense mutation Ser49Cys and risk of breast cancer
(2006
) |
| | In a combined analysis of breast cancer cases and controls from the USRT and Polish Breast Cancer Studies, we found convincing evidence that missense mutations in the ataxia telangiectasia gene (ATM) may be associated with increased breast cancer risk.
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| | [Abstract] [PubMed] |
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| CHEK2:1100delC and female breast cancer in the United States
(2004
) |
| | A genetic mutation in the CHEK2 gene (1100delC) was evaluated as a possible breast cancer susceptibility allele in two populations: a nested breast cancer case-control study within the USRT cohort and a study of families with breast/ovarian cancer. Investigators concluded that this mutation appears to be a rare allele that approximately doubles a carrier’s risk of breast cancer.
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| | [Abstract] |
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| Kin-cohort estimates for familial breast cancer risk in relation to variants in DNA base excision repair, BRCA1 interacting and growth factor genes
(2004
) |
| | A recently developed statistical method called "Kin Cohort" allowed us to evaluate the association of normal genetic variation (called polymorphisms) and breast cancer risk in family members. We analyzed 19 single nucleotide polymorphisms (SNPs) in eight genes related to DNA repair, growth regulation, and protein interaction with BRCA1. We assessed these SNPs and breast cancer risk among first-degree relatives (mothers, sisters, daughters) based on family history information. We found that two SNPs in a DNA repair gene and one SNP in a gene coding a BRCA1 interacting protein (BRIP1) were associated with increased breast cancer risk. However, because we analyzed so many variants at one time, when we adjusted for all of our comparisons none of the associations remained significant. We were surprised to find two polymorphisms (one in a DNA repair gene and another in BRCA2) that were significantly associated with decreased breast cancer risk. We plan to follow-up these interesting findings with additional studies.
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| | [Abstract] |
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| Re: Population-Based, Case-Control Study of HER2 Genetic Polymorphism and Breast Cancer Risk
(2003
) |
| | Using the same kin-cohort methodology described above, we also investigated breast cancer risk associated with a polymorphism in the human epidermal growth factor receptor 2 (HER2) protooncogene. We found an increased breast cancer risk up to age 70 associated with the polymorphic variant, but this was not statistically significant. However, the risk estimate was consistent with several previous reports, suggesting that risk may indeed be increased for breast cancer.
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| | [Abstract] [PubMed] |
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| Mutational analysis of the BRCA1-interacting genes ZNF350/ZBRK1 and BRIP1/BACH1 among BRCA1 and BRCA2-negative probands from breast-ovarian cancer families and among early-onset breast cancer cases and reference individuals
(2003
) |
| | We continued our research plan of finding and describing new polymorphisms in genes that associate with BRCA1 and to also try to discover new genes related to breast cancer susceptibility. Using some of the same 58 anonymous samples from radiologic technologists who developed breast cancer before age 35, two newly discovered genes (ZNF350 and BRIP1) were searched for polymorphisms. Several new polymorphisms were found that will be studied further in the US Radiologic Technologist study and likely epidemiologic studies of other populations.
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| | [Abstract] [PubMed] |
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| A single nucleotide polymorphism in the 5' untranslated region of RAD51 and risk of cancer among BRCA1/2 mutation carriers
(2001
) |
| | We tried the gene called RAD51 because it associates with BRCA1 and BRCA2 and it is involved in DNA repair. We wanted to see if genetic differences in RAD51 could impact whether someone with a BRCA1 or BRCA2 mutation might or might not get breast cancer. As described above, anonymous samples from 10 radiologic technologists who had multiple cancers (breast cancer and a cancer of another site) were included to discover variations in the RAD51 gene. The variations we searched for are called polymorphisms. Polymorphisms are different from mutations. Polymorphisms are considered to be normal genetic variation because they are common and on their own are not thought to be the cause of any specific disease. However, polymorphisms could be weakly related to disease, often in combination with other genes and environmental factors, but their effect can only be found if large population groups are studied. We discovered two new polymorphisms and tested them to see if they changed the risk of breast or ovarian cancer among several groups of women (not radiologic technologists) with BRCA1 or BRCA2 mutations. The results were mixed and depended on the group studied, but generally suggested an increased breast cancer risk for one of the polymorphisms and BRCA2.
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| | [Abstract] [PubMed] |
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| BRCA1 mutations in young women with breast cancer
(1996
) |
| | Since breast cancer has been associated with radiation exposure in several studies, including atomic bomb survivors, we are very interested in genes that could change how our cells handle damage caused by radiation. One of the first genes identified that strongly predisposes someone to breast cancer is BRCA1. Because the BRCA1 gene is involved in DNA repair, we thought this gene would be a good place to start. But, the genetic tests for BRCA1 mutations are extremely time consuming and expensive, we thought that picking some of the most common mutations and screening only for those in a high risk group (women who were diagnosed with breast or ovarian cancer at age 35 or younger), would be valuable for our research purposes. After we completely removed any and all information that would link an individual to a particular sample (we made the samples "anonymous"), we found that 3 of 70 had a mutation in BRCA1. We concluded this method would work as a crude screen to establish mutation frequencies in large population groups, but we estimated we would miss about 55% of women who were true carriers of a BRCA1 mutation. This meant that at least 4.3% of women who developed breast or ovarian cancer before age 35 are likely to have a BRCA1 mutation.
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| | [Abstract] [PubMed] |
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