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Jakubowska A.,Pomeranian Medical University | Rozkrut D.,University Of Szczecin | Antoniou A.,University of Cambridge | Hamann U.,German Cancer Research Center | And 120 more authors.
British Journal of Cancer | Year: 2012

Background: The variable penetrance of breast cancer in BRCA1/2 mutation carriers suggests that other genetic or environmental factors modify breast cancer risk. Two genes of special interest are prohibitin (PHB) and methylene-tetrahydrofolate reductase (MTHFR), both of which are important either directly or indirectly in maintaining genomic integrity. Methods: To evaluate the potential role of genetic variants within PHB and MTHFR in breast and ovarian cancer risk, 4102 BRCA1 and 2093 BRCA2 mutation carriers, and 6211 BRCA1 and 2902 BRCA2 carriers from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2 (CIMBA) were genotyped for the PHB 1630 C>T (rs6917) polymorphism and the MTHFR 677 C>T (rs1801133) polymorphism, respectively. Results: There was no evidence of association between the PHB 1630 C>T and MTHFR 677 C>T polymorphisms with either disease for BRCA1 or BRCA2 mutation carriers when breast and ovarian cancer associations were evaluated separately. Analysis that evaluated associations for breast and ovarian cancer simultaneously showed some evidence that BRCA1 mutation carriers who had the rare homozygote genotype (TT) of the PHB 1630 C>T polymorphism were at increased risk of both breast and ovarian cancer (HR 1.50, 95%CI 1.10-2.04 and HR 2.16, 95%CI 1.24-3.76, respectively). However, there was no evidence of association under a multiplicative model for the effect of each minor allele. Conclusion: The PHB 1630TT genotype may modify breast and ovarian cancer risks in BRCA1 mutation carriers. This association need to be evaluated in larger series of BRCA1 mutation carriers. © 2012 Cancer Research UK All rights reserved. Source


Kershenbaum A.,Clalit National Cancer Control Center | Flugelman A.,Clalit National Cancer Control Center | Lejbkowicz F.,Clalit National Cancer Control Center | Arad H.,Clalit National Cancer Control Center | Rennert G.,Clalit National Cancer Control Center
European Journal of Cancer | Year: 2013

Background: Faecal occult blood (FOB) testing is the most commonly chosen approach in organised population-based colorectal cancer screening programmes throughout the world. Several FOB tests are available which differ in their test qualities. While immunological tests are gaining popularity due to their lower labour intensive analysis and higher standardisation, they are heat labile and more expensive. We studied the real-life experience of a large population-based, organised, screening programme in Israel which employs FOB testing with Hemoccult Sensa, a guaiac test with increased sensitivity that is similar to that of the immunological tests for cancer. Methods: Clalit Health Services is the largest health care provider in Israel. All eligible insurees are actively invited to perform a free-of-charge, home-based, faecal occult blood test, using Hemoccult Sensa. All tests with positive results are followed up and information on colonoscopy, surgical procedures and pathology findings is collected. Results: During an 18 month period (July 2007-December 2008) 382,792 FOBT tests (in 325,851 people) were performed by the target population, of them 85% Jews and 15% Arabs. Seven hundred and eighteen colorectal cancers and 2652 adenomas were detected. The overall test positivity rate in repeatedly-tested people was 4.2%. The overall detection rate of colorectal cancer in the subsequent tests was 1.7/1000 reflecting 91% of the expected period-incidence of CRC. 70% of the cancers were detected at stages Duke's B2 and lower. Left-sided cancers were detected at a significantly better stage than right-sided cancers (P < 0.001). Detection rates among Arabs were somewhat lower than among Jews but the screening programme led to a meaningful increase in national incidence rate in this subgroup by detecting tumours that were otherwise asymptomatic. Conclusion: The Clalit organised colorectal cancer screening programme, using low cost Hemoccult Sensa, has reached the targets of very high detection rate of cancers, most of them at low stage while keeping a low positivity rate. This approach demonstrates an efficient field-tested alternative to other, more costly, screening options. © 2012 Elsevier Ltd. All rights reserved. Source

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