Sharon Teraoka

Degree(s): PhD Graduate School: University of California, Los Angeles Primary Appointment: Assistant Professor, Biochemistry and Molecular Genetics Research Interests: Genetic susceptibility to breast cancer, gene-environment interactions, and DNA damage response pathways. Email Address: st3x@virginia.edu

Research Description

The ATM Gene, Radiation, and Breast Cancer:  The WECARE Study

(Women’s Environment, Cancer and Radiation Epidemiology Study)

As a member of the laboratory section of the WECARE Study Consortium, I have been involved in mutation screening of the ATM, BRCA1, and BRCA2 genes in women with bilateral or unilateral breast cancer.   We are interested in the interaction of radiation exposure and genetic predisposition in the onset of breast cancer.  Previous studies have suggested ATM gene carriers are at increased risk for breast cancer.  ATM is a key regulator in the cellular response to DNA damage, a pathway that also includes BRCA1 and BRCA2, established breast cancer susceptibility genes.  Ionizing radiation, which can induce double strand breaks in DNA, is a known breast carcinogen.  In order to explore the complex relationship between ATM, radiation exposure and breast cancer, the WECARE (Women’s Environment, Cancer And Radiation Epidemiology) Study Consortium was formed by 17 international institutions.  In phase one of the WECARE Study, we hypothesized that women who carry a mutant allele in ATM, and who received radiation therapy for their first primary breast cancer, have an increased risk of developing a second primary breast cancer.  In our study, 700 women with asynchronous bilateral breast cancer were individually matched to 1400 controls with unilateral breast cancer, and counter-matched on radiation treatment.  Screening of the 62 coding exons of the ATM gene for all mutations and polymorphisms has been carried out at four of the WECARE sites utilizing denaturing high performance liquid chromatography (DHPLC) on the 2100 individuals.  In phase two of the WECARE Study, the BRCA1 and BRCA2 genes were screened for variants in the same sample set.  Follow-up studies include functional analyses of missense variants in ATM and haplotype analyses of variants in six genes of the ATM-Chk2 pathway of DNA damage response.

Selected Publications

• Bernstein JL, Teraoka S, Southey MC, Jenkins MA, Andrulis IL, Knight JA, John EM, Lapinski R, Wolitzer AL, Whittemore AS, West D, Seminara D, Olson ER, Spurdle AB, Chenevix-Trench G, Giles GG, Hopper JL, Concannon P (2006) Population-based estimates of breast cancer risks associated with ATM gene variants c.7271T>G and c.1066-6T>G (IVS10-6T>G) from the Breast Cancer Family Registry. Hum Mutat. 27(11):1122-8
• Bernstein JL, Teraoka S, John EM, Andrulis IL, Knight JA, Lapinski R, Olson ER, Wolitzer AL, Seminara D, Whittemore AS, Concannon P (2006) The CHEK2*1100delC allelic variant and risk of breast cancer: screening results from the Breast Cancer Family Registry. Cancer Epidemiol Biomarkers Prev. 15(2):348-52.
• Bernstein, JL, Teraoka, S, Haile, RW, Børresen-Dale, A-L, Rosenstein, BS, Gatti, RA, Diep, AT, Jansen, L, Atencio, DP, Olsen, JH, Bernstein, L, Teitelbaum, SL, Thompson, WD, the WECARE Study Collaborative Group and Concannon, PJ (2003) Designing and implementing quality control for multi-center screening of mutations in the ATM gene among women with breast cancer. Human Mutation 21:542-550.
• Teraoka, S., Malone, K., Doody, D., Suter, N., Ostrander, E., Daling, J., Concannon, P. (2001) Increased frequency of ATM mutations in breast carcinoma patients with early onset disease and positive family history. Cancer 92 (3): 479-487.

PubMed Listings for this Faculty Member