Original reportsCharacteristics Associated with Participation at Various Stages at the Ontario Site of the Cooperative Family Registry for Breast Cancer Studies
Introduction
It is known that genetics plays a role in the development of at least some breast cancers. One of the most consistently identified risk factors in this disease is having a first degree relative with breast cancer. This approximately doubles the risk (1). Mutations in the BRCA1 and BRCA2 genes are associated with a greater increase in risk in the small number of individuals who carry them, although estimates of risk vary 2, 3, 4. Other genetic alterations and variations have also been implicated with varying degrees of consistency in breast cancer development 5, 6. Many studies of breast cancer genetics, particularly of BRCA1 and BRCA2, have been carried out in families with multiple cases of breast and/or ovarian cancer. Although these families are useful for identifying high-risk mutations, they cannot be used to accurately determine the penetrance of the mutations in the population as any mutations in families with fewer cases and lower penetrance will be excluded.
The U.S. National Institutes of Health has created the Cooperative Family Registry for Breast Cancer Studies (CFRBCS) in order to develop a large resource including family history, epidemiologic, and clinical information as well as biospecimens to study the role of genetics in breast cancer. The CFRBCS consists of six sites, four based in the U.S., one in Australia, and one Ontario, Canada. Three of the U.S. sites accrue participants in the registry through high risk cancer genetics clinics, while the other three registries identify potential participants through population-based cancer registries. One of the goals of these sites is to obtain population-based measures of penetrance and prevalence of known genetic mutations and variations as well as conducting other population-based studies of genetics and breast cancer. Therefore, it is clearly important that the individuals recruited are as representative as possible of a defined population. In an effort to determine the extent of selection occurring in the Ontario registry, we analysed participation in cases diagnosed in 1996. We examined characteristics associated with response at different stages where a choice could be made about participation and where we had information available. This information included age, sex, and, for stages subsequent to the initial family history screening questionnaire, ethnicity, and family history. Of particular concern was whether response differed by the presence of a family history of breast and/or ovarian cancer.
Section snippets
The Ontario Familial Breast Cancer Registry
The Ontario Familial Breast Cancer Registry (OFBCR) uses a staged approach to recruiting participants to the registry, with follow-up occurring at all stages. The first step was the ascertainment of probands through the Ontario Cancer Registry (OCR). The OCR employs a passive voluntary system of registration of all cancers occurring in the over 10 million residents of Ontario. Studies carried out by the OCR estimate a completeness of case ascertainment for female breast cancer of 97.5% (7). For
Probands
We identified 2728 incident cases of invasive breast cancer (ICD9 174 and 175) diagnosed in 1996 with an available pathology report from the OCR. This included 1981 female cases aged 20 to 54 years, 718 female cases aged 55 to 69 years (sampled at 35%), and 29 male cases aged 20 to 79 years. Only 46 cases (1.7%) were excluded because they had died. Of the remaining 2682 cases, 13 were approached directly at cancer genetics clinics and physician contact was made for 2653 (99%) of the remaining
Discussion
Since our intention was to create a population-based registry, it was important to address the potential for bias among participants. Family history did not appear to affect participation, but women whose ethnicity was other than white and also men were less likely to participate than were white women. The results presented here were not altered by multivariate modelling. A particular concern was differential participation based on genetic risk. The agreement rate of physicians was very high
Acknowledgements
This work was supported by The Division of Cancer Epidemiology and Genetics, the National Cancer Institute of Health and Human Services, U01-CA69467, and by Cancer Care Ontario.
References (10)
- et al.
Frequency and carrier risk associated with common BRCA1 and BRCA2 mutations in Ashkenazi Jewish breast cancer patients
Am J Hum Genet.
(1998) - et al.
Population-based study of risk of breast cancer in carriers of BRCA2 mutation
Lancet.
(1998) - et al.
The Cooperative Familial Registry for Breast Cancer StudiesDesign and first year recruitment rates in Ontario
J Clin Epidemiol.
(2001) - et al.
Family history and the risk of breast cancerA systematic review and meta-analysis
Int J Cancer.
(1997) - et al.
Population-based estimate of the average age-specific cumulative risk of breast cancer for a defined set of protein-truncating mutations in BRCA1 and BRCA2
Cancer Epidemiol Biomark Prev.
(1999)
Cited by (30)
Does perceived risk predict breast cancer screening use? Findings from a prospective cohort study of female relatives from the Ontario site of the Breast Cancer Family Registry
2014, BreastCitation Excerpt :This study utilized data from a cohort of female relatives of incident cases of invasive breast cancer identified from the Ontario site of the Breast Cancer Family Registry (BCFR), funded by the United States National Cancer Institute. Details of the BCFR and the Ontario site of the BCFR have been previously described [36,37]. Briefly, cases of pathologically-confirmed invasive breast cancer (probands), diagnosed between 1996 and 1998 were identified from the Ontario Cancer Registry.
Identification of rare variants in the hLIMD1 gene in breast cancer
2007, Cancer Genetics and CytogeneticsCitation Excerpt :Subsequent to the diagnosis of invasive cancer, tumor specimens were cataloged by a pathologist, snap frozen, and stored in liquid nitrogen. Blood DNA from 70 patients with familial breast cancer was obtained form the Ontario site [27] of the Breast Cancer Family Registry [28]. Blood DNA from individuals unselected for cancer was used in the molecular analysis.
Ethnicity, but not cancer family history, is related to response to a population-based mailed questionnaire
2004, Annals of EpidemiologyFresh Cut Versus Stored Cut Paraffin-embedded Tissue: Effect on Immunohistochemical Staining for Common Breast Cancer Markers
2019, Applied Immunohistochemistry and Molecular Morphology