Breast and Prostate Cancer and Hormone-Related Gene Variant Study
Breast and Prostate Cancer Cohort Consortium (BPC3)
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) 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.
Division of Cancer Epidemiology and Genetics, NCI
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.
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) 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.
National Cancer Institute |
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.
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