Major Research Projects
In 1995, the National Cancer Institute established the Breast Cancer Family Registry, an international consortium, for interdisciplinary and translational studies of the genetic epidemiology of breast cancer. http://epi.grants.cancer.gov/CFR/ The six collaborating family registries in the U.S. (San Francisco Bay area, New York City, Philadelphia and Utah), Ontario, Canada and Melbourne/Sydney, Australia, have enrolled over 15,000 breast cancer families. Using common protocols and questionnaires, data and biospecimens have been collected for breast cancer patients and family members. Available resources include 1) interview data on family history of breast and other cancers; hormonal, lifestyle and other factors; dietary intake based on a food frequency questionnaire; and self-reported treatment information for individuals diagnosed with breast cancer; and 2) biospecimens, such as blood or mouthwash samples, and archived tumor tissue for individuals diagnosed with breast cancer. Registry participants have been followed-up annually in order to assess the occurrence of new cancers in the family. A more intensive follow-up was initiated in 2007.
The Northern California site covering the nine counties of the Greater San Francisco Bay area has recruited over 3,000 families, including 2,200 (73%) families from racial/ethnic minority groups. Recruitment of an additional 800 African-American and Hispanic families in continuing and has been expanded into the Sacramento area. Participating family members are kept informed through an annual newsletter (see below).
Principal Investigator: Esther M. John, Ph.D.
The data and biospecimen resources from the six collaborating family registries are available to qualified researchers worldwide. Confidentiality is maintained by the assignment of a study identification number to each registry participant. No personal information such as names or contact information is shared with collaborating researchers. Applications to use the resources are reviewed by a Scientific Advisory Board (for information on application process, consult http://epi.grants.cancer.gov/CFR/). To date, the Advisory Board has approved over 100 research studies on a wide range of topics. Below is a listing of studies initiated by investigators at the Northern California site and collaborative studies the Northern California site has participated in.
BRCA1 and BRCA2 Mutations in Minority Families
Genetics of Breast Cancer in Blacks
Breast Cancer Risk Modifiers in BRCA Mutation Carriers
Cancer Risk in Relatives of Breast Cancer Patients
The first study led by Dr. Jennifer Lee, Stanford University pooled data from the Northern California site of the Breast Cancer Family Registry and the Family Registry for Ovarian Cancer and examined the incidence of breast and ovarian cancer in first-degree relatives of breast and ovarian cancer patients enrolled in these two family registries, and assessed whether the risks in relatives vary by the patient's cancer site, carrier status of predisposing genetic mutations, or age at cancer diagnosis.
The second study led by Dr. Gillian Dite, University of Melbourne, examined the incidence of breast and other cancers in first- and second-degree relatives of early-onset breast cancer patients (diagnosed under age 35 years) that are enrolled in the three population-based sites of the Breast Cancer Family Registry (Northern California, Ontario Canada, and Melbourne/Sydney Australia).
Case-control Analyses of Breast Cancer Risk Factors
The Role of the ATM Gene in Familial Breast Cancer
IGF Signaling Pathway and Breast Cancer Risk
Genetics Studies of Mammographic Density
Prognosis in BRCA1 Associated Breast Cancer
Daly MB, Offit K, Li F, Glendon G, Yaker A, West DW, Koenig B, McCredie M, Venne V, Nayfield S, Seminara D. Participation in the Cooperative Family Registry for Breast Cancer studies: issues of informed consent. J Natl Cancer Inst 2000; 92(6):452-456.
Beck JC, Beiswanger CM, John EM, Satariano E, West DW. Successful transformation of cryopreserved lymphocytes: a resource for epidemiological studies. Cancer Epidemiol Biomarkers Prev 2001;10:551-54.
Thompson D, Szabo CI, Mangion J, Oldenburg RA, Odefrey F, Seal S, Barfoot R, Kroeze-Jansema K, Teare D, Rahman N, Renard H, Mann G, Hopper JL, Buys SS, Andrulis IL, Senie RT, Daly MB, West D, Ostrander EA, Offit K, Peretz T, Osorio A, Benitez J, Nathanson KL, Sinilnikova OM, Olah E, Bignon YJ, Ruiz P, Badzioch MD, Vasen HF, Futreal AP, Phelan CM, Narod SA, Lynch HT, Ponder BA, Eeles RA, Meijers-Heijboer H, Stoppa-Lyonnet D, Couch FJ, Eccles DM, Evans DG, Chang-Claude J, Lenoir G, Weber BL, Devilee P, Easton DF, Goldgar DE, Stratton MR; KConFab Consortium. Evaluation of linkage of breast cancer to the putative BRCA3 locus on chromosome 13q21 in 128 multiple case families from the Breast Cancer Linkage Consortium. Proc Natl Acad Sci U S A 2002;99(2):827-31.
Lin SS, Clarke CA, O'Malley CD, Le GM. Studying cancer incidence and outcomes in immigrants: methodological concerns. Am J Public Health 2002 Nov;92(11):1757-9.
Andrulis IL, Anton-Culver H, Beck J, Bove B, Boyd J, Buys S, Godwin AK, Hopper JL, Li F, Neuhausen SL, Ozcelik H, Peel D, Santella RM, Southey MC, van Orsouw NJ, Venter DJ, Vijg J, Whittemore AS, Cooperative Family Registry for Breast Cancer Studies. Comparison of DNA- and RNA-based methods for detection of truncating BRCA1 mutations. Hum Mutat 2002;20(1):65-73.
Whittemore AS, Balise RR, Pharoah PDP, DiCioccio RA, Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab)4, Oakley-Girvan I, Ramus SJ, Daly M, Usinowicz MB, Garlinghouse-Jones K, Ponder BAJ, Buys S, Senie R, Andrulis I, John E, Hopper JL, Piver MS. Oral contraceptive use and ovarian cancer risk among carriers of BRCA1 or BRCA2 mutations. Br J Cancer 200
Whittemore AS, Balise RR, Pharoah PD, Dicioccio RA, Oakley-Girvan I, Ramus SJ, Daly M, Usinowicz MB, Garlinghouse-Jones K, Ponder BA, Buys S, Senie RT, Andrulis I, John E, Hopper JL, Piver MS. Oral contraceptive use and ovarian cancer risk among carriers of BRCA1 or BRCA2 mutations. Br J Cancer 2004;91(11):1911-5.
John EM, Hopper JL, Beck JC, Knight JA, Neuhausen SL, Senie RT, Ziogas A, Andrulis IL, Anton-Culver H, Boyd N, Buys SS, Daly MB, O'Malley FP, Santella RM, Southey MC, Venne VL, Venter DJ, West DW, Whittemore AS, Seminara S, for the Breast Cancer Family Registry. The Breast Cancer Family Registry: an infrastructure for cooperative multinational, interdisciplinary and translational studies of the genetic epidemiology of breast cancer. Breast Cancer Research 2004; 6(4):R375-R389.
Gomez SL, Glaser SL. Quality of birthplace information obtained from death certificates for Hispanics, Asians, and Pacific Islanders. Ethn Dis 2004;14(2):292-5.
Milne RL, Knight JA, John EM, Dite GS, Balbuena R, Ziogas A, Andrulis IL, West DW, Li FP, Southey MC, Giles GG, McCredie MR, Hopper JL, Whittemore AS. Oral contraceptive use and risk of early-onset breast cancer in carriers and noncarriers of BRCA1 and BRCA2 mutations. Cancer Epidemiol Biomarkers Prev 2005 Feb;14(2):350-6.
Gomez SL, Glaser SL. Quality of cancer registry birthplace data for Hispanics living in the United States. Cancer Causes Control 2005 Aug;16(6):713-23.
Ahsan H, Whittemore AS, Chen Y, Senie RT, Hamilton SP, Wang Q, Gurvich I, Santella RM. Variants in estrogen-biosynthesis genes CYP17 and Cyp19 and breast cancer risk: a family-based genetic association study. Breast Cancer Res 2005;7(1):R71-81.
Turner-Cobb JM, Bloor LE, Whittemore AS, West D, Spiegel D. Disengagement and social support moderate distress among women with a family history of breast cancer. Breast J 2006 Jan-Feb;12(1):7-15.
Spurdle AB, Antoniou AC, Duffy D, Kelemen L, Holland H, Peock S, Cook MR, Smith PL, Greene MH, Simard J, Plourde M, Southey M, Godwin A, Beck J, Miron A, Daly M, Santella R, Hopper J, John EM, Andrulis I, Durocher F, Struewing, JP, Easton DF, Chenevix-Trench G, Australian Breast Cancer Family Study, Australian Jewish Breast Cancer Study, Breast Cancer Family Registry, Interdisciplinary Health Research International Team on Breast Cancer Susceptibility, The Kathleen Cunningham Foundation Consortium for Research into Familial Breast Cancer, and Epidemiological Study of Familial Breast Cancer Study Collaborators. The AIB1 polyglutamine repeat does not modify breast cancer risk in BRCA1 and BRCA2 mutation carriers. Cancer Epidemiol Biomarkers Prev 2006 Jan;15(1):76-9.
McGuire V, John EM, Felberg A, Haile RW, Boyd NF, Thomas DC, Jenkins MA, Milne RL, Daly MB, Ward J, Terry MB, Andrulis IL, Knight JA, Godwin AK, Giles GG, Southey M, West DW, Hopper JL, Whittemore AS, kConFab Investigators. No increased risk of breast cancer associated with alcohol consumption among carriers of BRCA1 and BRCA2 mutations ages <50 years. Cancer Epidemiol Biomarkers Prev 2006 Aug;15(8):1565-7.
Knight JA, John EM, Milne RL, Dite GS, Balbuena R, Shi EJ, Giles GG, Ziogas A, Andrulis IL, Whittemore AS, Hopper JL; Breast Cancer Family Registry. An inverse association between ovarian cysts and breast cancer in the Breast Cancer Family Registry. Int J Cancer 2006 Jan 1;118(1):197-202.
Gomez SL, Glaser SL. Misclassification of race/ethnicity in a population-based cancer registry (United States). Cancer Causes Control 2006 Aug;17(6):771-81.
Bernstein JL, Teraoka S, Southey MC, Jenkins MA, Andrulis IL, Knight JA, John EM, Lapinski RH, Wolitzer AL, Whittemore AS, West DW, Seminara D, Olson ER, Spurdle AB, Chenevix-Trench G, Giles GG, Hopper JL, Concannon P. Population-based estimates of breast cancer risks associated with ATM gene variants c.T7271T>G and c.1066-6T>G (IVS10-6T>G) from the Breast Cancer Family Registry. Human Mutation 2006;27(11):1122-8.
Bane AL, Beck JC, Bleiweiss I, Buys SS, Catalano E, Daly MB, Giles G, Godwin AK, Hisbshoosh H, Hopper JL, John EM, Layfield L, Longacre T, Miron A, Senie R, Southey MC, West DW, Whittemore AS, Wu H, Andrulis IL, O'Malley FP. BRCA2 mutation-associated breast cancers exhibit a distinguishing phenotype based on morphology and molecular profiles from tissue microarrays. Am J Surg Pathol 2007;31(1):121-8.
Terry MB, Knight JA, Zablotska L, Wang Q, John EM, Andrulis IL, Senie RT, Daly M, Ozcelik H, Briollais L, Santella RM. Alcohol metabolism, alcohol intake, and breast cancer risk: a sister-set analysis using the Breast Cancer Family Registry. Breast Cancer Res Treat 2007 Feb 1 [Epub ahead of print] (in press).
John EM, Phipps AI, Knight JA, Milne RL, Dite GS, Hopper JL, Andrulis IL, Southey M, Giles GG, West DW, Whittemore AS. Medical radiation exposure and breast cancer risk: Findings from the Breast Cancer Family Registry. Int J Cancer 2007;121:386-94.
Hong AL, Huo D, Kim HJ, Chen YS, Niu Q, Cummings SA, John EM, West DW, Whittemore AS, Das S, Olopade OI. UDP-Glucuronosyltransferase 1A1 gene polymorphisms and total bilirubin levels in an ethnically diverse cohort of women. Drug Metab Disposition 2007, 2007;35:1254-61.
Apicella C, Dowty JG, Dite GS, Jenkins MA, Senie R, Daly MB, Andrulis IL, John EM, Buys SS, Li FP, Glendon G, Chung W, Ozcelik H, Miron A, Kotar K, Southey MC, Foulkes W, Hopper JL. Validation study of the LAMBDA model for predicting the BRCA1 or BRCA2 mutation carrier status of North American Ashkenazi Jewish women. Clin Genet 2007, 72:87-97.
John EM, Miron A, Gong G, Phipps AI, Felberg I, Li FP, West DW, Whittemore AS. Prevalence of pathogenic BRCA1 mutation carriers in five US racial/ethnic groups. JAMA 2007;298(24):2869-76.
Garner CP, Diny YC, John EM, Ingles SA, Olopade OF, Huo D, Adebamowo C, Ogundiran T, Neuhausen SL. Genetic variation in IGFBP2 and IGFBP5 is associated with breast cancer risk in populations of African descent. Hum Genet 2008; 123(3):247-55.
Kibriya MG, Jasmine F, Argos M, Andrulis IL, John EM, Chang-Claude J, Ahsan H. A genome-wide association study of early-onset breast cancer among BRCA1- and BRCA2-negative Caucasian women. Breast Cancer Res & Treatment 2008 May 8 [Epub ahead of print].
Rebbeck TR, Antoniou AC, Llopis TC, Nevanlinna H, Aittomaki K, Simard J, Spurdle AB, KConFab, Couch FJ, Pereira LH, Greene MH, Andrulis IL, Ontario Cancer Genetics Network, Pasche B, Kaklamani V, Breast Cancer Family Registry, Hamann U, Szabo C, Peock S, Cook M, Harrington PA, Dondaldson A, Male AM, Gardiner CA, Gregory H, Side LE, Robinson AC, Emmerson L, Ellis I, EMBRACE, Peyrat JP, Fournier J, Vennin P, Adenis C, Muller D, Fricker JP, Longy M, Sinilnikova OM, Stoppa-Lyonnet D, GEMO, Schmutzler RK, Versmold B, Engel C, Meindle A, Kast K, Schaefer D, Froster UG, Chenevix-Trench G, Easton DF. No association of TGFB1 L10P genotypes and breast cancer risk in BRCA1 and BRCA2 mutation carriers: a multi-center cohort study. Breast Cancer Res Treat 2008; Jun 4. [Epub ahead of print]
Neuhausen SL, Ozcelik H, Southey MC, John EM, Godwin AK, Chung W, Iriondo-Perez J, Miron A, Santella RM, Whittemore AS, Andrulis IL, Buys SS, Daly MB, Hopper JL, Seminara D, Senie RT, Terry MB, for the Breast Cancer Family Registry. BRCA1 and BRCA2 mutation carriers in the Breast Cancer Family Registry: an open resource for collaborative research. Breast Cancer Res & Treatm 2008 Aug 14. [Epub ahead of print]
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