In:
Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 23, No. 11_Supplement ( 2014-11-01), p. PL03-01-PL03-01
Kurzfassung:
Epithelial ovarian cancer (EOC) is the 5th leading cause of cancer-related deaths in women in the United States1. High-grade serous carcinoma (HGSC) is the most aggressive EOC and women usually present at high-grade and high stage, leading to only a 30% 5 year survival rate after adjuvant platinum-based chemotherapy2. Women who have an inherited mutation in the BRCA1 or BRCA2 genes have a substantial increased lifetime risk (11%-60%) in developing high-grade serous cancer – the predominant histotype associated with hereditary breast-ovarian cancer3. The distal end of the fallopian tube is now the accepted site of origin of high-grade serous ovarian cancer4. It is known that factors related to parity, ovulation and hormone regulation have a dramatic effect on the risk of developing ovarian cancer in both BRCA mutation carriers and non-carriers. Recently, we have shown that the transcriptional profile of histologically normal fallopian tube epithelia of BRCA mutation carriers is different from wild type FTE and possibly hints at BRCA haploinsufficiency5,6. We propose that changes of the transcriptome in BRCA mutation carriers reflect an altered response to the microenvironment ovulatory stresses, which may include altered reproductive hormone levels and the ovulatory inflammatory response. The prevalence of the BRCA mutation in the Bahamas where 23% of unselected breast cancer patients carry a mutation in the BRCA1 is the highest hereditary proportion in the world7,8. We are determining the importance of genetic founder effects in the two BRCA genes in the Caribbean basin - a region with a large African population (the Caymans, Barbados, Dominica and Jamaica). Epithelial ovarian cancer rates are low in the Caribbean and risk factors such as parity, age at menarche and menopause may be strong indicators of decreased risk in the population. The results of this extensive study will help direct health policies towards genetic testing in the Caribbean with implications for the immigrant US population, and should lead to regional policies regarding preventative strategies. References: 1 Siegel, R., Naishadham, D. & Jemal, A. Cancer statistics, 2013. CA: A Cancer Journal for Clinicians 63, 11-30, doi:10.3322/caac.21166 (2013). 2 Coleman, M. P. et al. Cancer survival in Australia, Canada, Denmark, Norway, Sweden, and the UK, 1995-2007 (the International Cancer Benchmarking Partnership): an analysis of population-based cancer registry data. Lancet 377, 127-138, doi:10.1016/S0140-6736(10)62231-3 (2011). 3 Foulkes, W. D. & Narod, S. A. Ovarian cancer risk and family history. Lancet 349, 878, doi:S0140-6736(05)61782-5 [pii]10.1016/S0140-6736(05)61782-5 (1997). 4 Vang, R., Shih Ie, M. & Kurman, R. J. Fallopian tube precursors of ovarian low- and high-grade serous neoplasms. Histopathology 62, 44-58, doi:10.1111/his.12046 (2013). 5 George, S. H., Milea, A. & Shaw, P. A. Proliferation in the normal FTE is a hallmark of the follicular phase, not BRCA mutation status. Clinical cancer research : an official journal of the American Association for Cancer Research 18, 6199-6207, doi:10.1158/1078-0432.CCR-12-2155 (2012). 6 George, S. H. et al. Identification of abrogated pathways in fallopian tube epithelium from BRCA1 mutation carriers. The Journal of pathology 225, 106-117, doi:10.1002/path.2927 (2011). 7 Akbari, M. et al. The spectrum of BRCA1 and BRCA2 mutations in breast cancer patients in the Bahamas. Clinical genetics, doi:10.1111/cge.12132 (2013). 8 Donenberg, T. et al. A high prevalence of BRCA1 mutations among breast cancer patients from the Bahamas. Breast cancer research and treatment 125, 591-596, doi:10.1007/s10549-010-1156-9 (2011). Citation Format: Sophia H.L. George, Sophia H.L. George, Judith Hurley, Talia Donenberg, Hedda Dyer, Anca Milea, Anca Milea, Patricia A. Shaw, Patricia A. Shaw, Patricia A. Shaw. Origins of ovarian cancer, the biology of premalignancy, and cancer health disparities. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr PL03-01. doi:10.1158/1538-7755.DISP13-PL03-01
Materialart:
Online-Ressource
ISSN:
1055-9965
,
1538-7755
DOI:
10.1158/1538-7755.DISP13-PL03-01
Sprache:
Englisch
Verlag:
American Association for Cancer Research (AACR)
Publikationsdatum:
2014
ZDB Id:
2036781-8
ZDB Id:
1153420-5
