BPC3 Cohorts and Working Groups
To achieve the goals of the consortium, several working groups have been created that coordinate the efforts within and across the participating cohorts and scientific disciplines. These structures are:
- Steering Committee: The Steering Committee includes the four principal investigators for the cooperative agreements that fund participation of the cohorts in the BCP3 Study, the principal investigators of the cohorts themselves (which are funded independent of this study), and NCI Program staff as Ex Officio members. The Steering Committee coordinates the activities of the research components, decides on a timeline for specific subcomponents of the study (e.g., the order in which groups of genes are genotyped), coordinates pooling of data, and distributes parts of the pooled data analyses to BCP3 Study members.
- Secretariat: Drs. David Hunter and Elio Riboli were elected co-chairs of the Steering Committee and serve as the Secretariat responsible for coordinating meetings, conference calls, and communications with NCI.
- Shared resources:
- Population Genetics Working Group
- Haplotype Determination Laboratories
- Genotyping Working Group
- Statistics Working Group
- Data Pooling Working Group
- Publications Working Group
- Community Web Site Working Group
Overview of Cohorts in the BPC3
The table below briefly summarizes information about the participating cohorts in the BPC3. These cohorts had accrued >500 cases of invasive breast and/or >500 cases of prostate cancer by the end of 2000. All of the cohorts are supported by funding independent of the BPC3 Study.
| Cohort | Year Cohort Established | Principal Investigator of BPC3/Institution | Total Number With DNA Samples | Breast Cancer Cases | Prostate Cancer Cases |
|---|---|---|---|---|---|
| American Cancer Society (CPS-II) | 1998 | Michael J. Thun, M.D., M.S. American Cancer Society |
39,000 | 500 a | 1,450 c |
| European Prospective Investigation Into Cancer and Nutrition (EPIC) | 1992 | Elio Riboli, M.D., M.P.H., M.Sc. Imperial College, London |
397,256 | 2050 a | 900 a |
| Harvard Cohorts | |||||
 Physicians' Health Study (PHS) I d |
1982 | David J. Hunter, M.B.B.S.,
Sc.D. Channing Laboratory, Harvard School of Public Health |
20,000 | - | 1,500 |
| Nurses' Health
Study (NHS) I d |
1976 | 32,826 | 945 b | - | |
| Nurses' Health
Study (NHS) II d |
1989 | ||||
| Health Professionals Follow-up Study (HPFS) d |
1993 | 33,240 | - | 600 | |
| Women's Health Study (WHS) d |
1993 | 28,263 | 675 b | - | |
| Multiethnic Cohort Study (MEC) d, e | Brian E. Henderson, M.D. University of Southern California |
100,000 e | 1,990 c | 2,400 c | |
| Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) d | 1993 | Richard B. Hayes, D.D.S., Ph.D. NYU Langone Medical Center |
75,000 | - | 1,000 |
| Alpha-Tocopherol Beta-Carotene (ATBC) Study | 1991 | Demetrius Albanes, M.D. National Cancer Institute |
20,500 | - | 1,000 |
| Total | 746,085 | 6,160 | 8,850 | ||
a Includes cases available for genotyping by mid-2001.
b Includes cases available for genotyping by the end of 2000.
c Includes cases available for genotyping by the end of 2002.
d In this instance, the principal investigator for the cohort differs from
the principal investigator for the BPC3.
e Blood available for cancer cases and a subcohort of 5000 controls. Additional
blood collection is underway.
The cooperative agreements, which were awarded in 2003 and continued in the fall of 2007 for four additional years, fund the participation of these cohorts and principal investigators in the Breast and Prostate Cancer and Hormone-Related Gene Variant Study:
American Cancer Society's Cancer Prevention Study-II
(ACS CPS-II)
Michael J. Thun, M.D., M.S.
American Cancer Society
The American Cancer Society Cancer Prevention Study II Nutrition Cohort (CPS-II) was established in 1992. The cohort includes more than 86,000 men and 97,000 women who completed a mailed questionnaire in 1992. Starting in 1997, follow-up questionnaires have been sent to surviving cohort members every other year to update exposure information and to ascertain occurrence of new cases of cancer; a 90% response rate was achieved for follow-up questionnaires in 1997 and 1999. Incident cancers are verified through medical records, state cancer registries, or death certificates. From June 1998 through June 2001, blood samples were collected from a subgroup of 39,376 cohort members. The CPS-II has accrued 500 cases of breast cancer (and their age and race-matched controls) and 1,450 cases of prostate cancer (and their age and race-matched controls) who were diagnosed after completing the 1992 questionnaire and who gave a single blood sample during the period June 1998 through June 2001. For all cases, exposure information was collected by questionnaire before the cancer diagnosis. However, collection of blood samples occurred after cancer diagnosis or immediately preceding cancer diagnosis. Thus, these cases are eligible for the genetic analyses but not for comparisons of prediagnostic plasma hormone levels.
European Prospective Investigation into Cancer and
Nutrition (EPIC) Study
Elio Riboli, M.D., Sc.M., M.P.H.
Imperial College, London
(formerly with the International Agency for Research on Cancer)
The European Prospective Investigation into Cancer and Nutrition (EPIC) Study is a multicenter prospective study initiated in 1992, and initially comprising 17 study centers in 7 countries. Subsequently, five additional study centers in three other countries (Sweden, Denmark, and Norway) became associated centers. Recruitment began in 1992 and ended in 1998 (in Norway recruitment is still ongoing). As of October 2001, the EPIC Study included 397,256 women and men, who had provided questionnaire data on diet and non-dietary variables, anthropometric measurements, and buffy coat, plasma, serum, and erythrocyte samples. For most of the EPIC centers (all centers in Spain, Italy, the Netherlands, the United Kingdom, Denmark, Sweden, and Norway), follow-up on cancer incidence and vital status is performed by record linkage with cancer and mortality registries. In Germany, Greece, and France, active follow-up mechanisms have been implemented to obtain information from the study participants and their next-of-kin. Cancer diagnoses are then confirmed with medical records and/or death certificates. The EPIC Study includes 2,050 cases of breast cancer and 900 cases of prostate cancer that are available to the BPC3.
Harvard Cohorts
David J. Hunter, M.B.B.S., Sc.D.
Channing Laboratory, Harvard School of Public Health
There are four Harvard Cohorts participating in the BPC3. The Physicians'
Health Study (PHS) I was a randomized trial of low-dose aspirin and beta-carotene
in the prevention of cardiovascular disease and cancer in men aged 40-84
at entry in 1982. This population was supplemented in 1999 with male
physicians aged 50 years or older; more than 20,000 men provided baseline
blood samples. The Nurses'
Health Study (NHS) consists of 121,700 women
enrolled in 1976. In 1989-90, 32,826 participants provided a blood sample.
The Health Professionals
Follow-up Study (HPFS) consists of 51,529 non-physician
health professionals (e.g., dentists and veterinarians) of whom 18,410
gave a blood sample in 1993 and 15,100 gave buccal cell samples in 1999.
The Women's Health
Study (WHS) is a randomized trial of low-dose aspirin
and vitamin E for the prevention of cardiovascular disease and cancer
among 39,876 female health professionals aged 45 years or older at baseline
in 1993; 28,263 women provided blood samples prior to randomization.
Cancer follow-up in all these cohorts is conducted by personal mailings and searches of the National Death Index and is estimated to be greater than 90%. All participants diagnosed with cancer are asked for permission to review medical records to confirm the diagnoses and obtain additional information on tumor histology, staging, and other characteristics (e.g., receptor status for breast cancers). (The principal investigators for these cohorts differ from the principal investigator for the BPC3. PHS: J. Michael Gaziano, M.D., M.P.H. and Meir J. Stampfer, M.D., Dr.P.H.; NHS: Graham A. Colditz, M.D., Dr.P.H. and Frank Speizer, M.D.; HPFS: Walter C. Willett, M.D., Dr.P.H.; WHS: Julie Buring, Sc.D.)
Multiethnic
Cohort Study (no web site)
Brian E. Henderson, M.D.
University of Southern California/Norris Comprehensive Cancer Center
Between 1993 and 1996, participants entered the Hawaii/Los Angeles Multiethnic Cohort (MEC) Study after completing and returning a baseline questionnaire that asked detailed dietary, demographic, and other information. The MEC Study consists of 215,251 men and women (ages 45-75 years at baseline) from Hawaii (Asians, Whites, and Native Hawaiians) and California (African-Americans and Latinos). Incident cancer cases are ascertained through population-based tumor registries. Cases and matched controls are contacted to obtain blood samples with a 70% success rate. A biological specimen bank is being established that will include: 1) samples collected after diagnosis from 6,500 incident breast, prostate, and colorectal cancer cases; and 2) prospectively collected biospecimens from approximately 100,000 cohort participants. For the BPC3 Study, data are being drawn from 1,990 breast cancer cases and 2,400 prostate cancer cases in the MEC Study. This resource provides the opportunity to evaluate the genetic and biochemical determinants of cancer risk in traditionally understudied minority populations. (The principal investigators for this cohort (Laurence N. Kolonel, M.D., Ph.D. and Brian E. Henderson, M.D.) differ from the principal investigator for the BPC3).
Two of the cohorts are part of the Division of Cancer Epidemiology and Genetics Research (DCEG), which is an intramural research arm of NCI:
Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer
Screening Trial
Richard B. Hayes, D.D.S., Ph.D.
NYU Langone Medical Center
The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial is a multi-institution study sponsored and coordinated by NCI. The PLCO has enrolled more than 154,000 men and women in a large-scale clinical trial to determine whether certain cancer screening tests reduce deaths from prostate, lung, colorectal, and ovarian cancer. Participants 55-74 joined the trial between 1992 and 2001 at 10 centers across the country. Half of these participants were selected by chance to receive specific screening tests and half receive routine care by their personal health care providers. All participants provide regular updates on a variety of health measurements in an annual questionnaire, as well as blood samples for use in studies of biologic markers of cancer risk. Half of participants in the screening arm have had blood samples taken at baseline. Data for the BPC3 are being drawn from 1,000 cases of prostate cancer in the PLCO Trial. (The principal investigators for this cohort (Richard B. Hayes, D.D.S., Ph.D. and John Gohagan, Ph.D.) differ from the principal investigator for the BPC3.)
Alpha-Tocopherol, Beta-Carotene Cancer Prevention
(ATBC) Study
Demetrius Albanes, M.D.
Division of Cancer Epidemiology and Genetics, NCI
The Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study was a cancer prevention trial conducted by NCI and the National Public Health Institute of Finland from 1985 to 1993. The study was to determine whether certain vitamin supplements would prevent lung cancer and other cancers in a group of 29,133 male smokers 50-69 years old in Finland. The 50- to 69-year-old participants took a pill daily for five to eight years that contained one of the following: 50 milligrams (mg) alpha-tocopherol (a form of vitamin E), 20 mg of beta-carotene (a precursor of vitamin A), both, or a placebo (inactive pill that looked like the vitamin). Questionnaire data and blood samples were collected at baseline and during follow-up. Incident cancer cases are identified annually through national registers. Data on 1,180 cases of prostate cancer are being drawn from the ATBC Study for the BPC3.
