- Email: [email protected]
P0127 Curcuminoids as putative ebv lytic induction agents for adjuvant treatment in EBV-positive carcinoma
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Abstracts / 50 (2014) e1–e74
Methods: Fifty patients were studied for 36 months. The patients had large volume resections and underwent immediate partial breast reconstruction with lattisimus dorsi flap. Oncological safety was assessed by margin status, and cosmetic outcomes by photographs at 1 month, 3 months, 6 months, and 1 year. Questionnaires were used to evaluate patients’ personal experiences after the reconstruction. Subjective cosmetic assessments were made with LENT–SOMA SCORE. Findings: Patients’ were aged 20–65 years. Surgery was for primary breast cancer in 45 patients, and after neoadjuvant chemotherapy in five. Operating time ranged from 110 to 210 min (mean 153.9 min. Mean blood loss was 134.2 mL (range 75–350). Volume of resection was 30 to 300 cc. The skin island used for volume replacement was 4 cm 3 cm to 14 cm 6 cm. No patients had positive or close margins. Major wound complications occurred in three patients, and minor wound complications in five. Seven patients had seroma and three had lymphoedema. After follow up for 12 to 23 months, 46 patients had scores of 3 or more, while four had a score of less than 3. Interpretation: Oncoplasty is oncologically safe with good cosmetic outcome. Integration of oncoplasty techniques broadens the horizon for breast conservation surgery. Different techniques have to be individually tailored for better results. http://dx.doi.org/10.1016/j.ejca.2014.03.168
P0125 EFFECT OF THE COMBINATION OF FRONDOSIDE A WITH OXALIPLATIN OR FLUOROURACIL IN THE TREATMENT OF COLON CANCER S. Attoub a,*, K. Arafat a, R. Iratni b. a Department of Pharmacology & Therapeutics, College of Medicine & Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates, b Department of Biology, College of Science, United Arab Emirates University, Al-Ain, United Arab Emirates Background: Colorectal cancer is the third leading cause of cancer deaths in the world despite many therapeutic options. We have demonstrated that frondoside A, a triterpenoid glycoside isolated from an Atlantic sea cucumber, has potent in vitro and in vivo anticancer effects against human pancreatic, breast, and lung cancer. We also demonstrated that frondoside A was able to potentiate and/or to synergise the anti-cancer effects of gemcitabine, paclitaxel, and cisplatin in the treatment of pancreatic, breast, and lung cancer, respectively. These results suggest that frondoside A may have an anticancer potential in the treatment of colon cancer either alone, and/or in combination, with the standard cytotoxic drugs oxaliplatin and fluorouracil. Methods: The impact of the treatments on cellular proliferation and apoptosis was determined using cell counter, FACS analysis, and caspase activities. Findings: Frondoside A, oxaliplatin, and fluorouracil induced a concentration-dependent and time-dependent inhibition of cellular proliferation and induced apoptosis in a caspase-dependent manner in the three colorectal cancer cells HT29, HCT116, and HCT8/S11. Combinations of low concentrations of these drugs for 48 h in vitro indicate that frondoside A enhances the inhibition of cell proliferation and the induction of apoptosis mediated by oxaliplatin as well as by fluorouracil. Interpretation: We believe that frondoside A will improve colon cancer therapy in combination with the standard cytotoxic drugs oxaliplatin and fluorouracil.
P0126 CYTOLYTIC VIRUS ACTIVATION THERAPY EPSTEIN-BARR VIRUS DRIVEN TUMOURS
A.E. Greijer a, S.D. Stoker b, Z. Novalic a, O. Malik a, S.A.W.M. Verkuijlen a, H. Juwana a, A.D.R. Huitema c, B.I. Tan b, J.P. de Boer d, S.H. Hutajulu e, J. Kurnianda e, J.M. Middeldorp a,*. a Department of Pathology, VU University Medical Center, Amsterdam, the Netherlands, b Department of Head & Neck Oncology-Surgery, Netherlands Cancer Institute-Antony van Leeuwenhoek Hospital, Amsterdam, The Netherlands, c Department of Pharmacology, Netherlands Cancer Institute-Antony van Leeuwenhoek Hospital, Amsterdam, The Netherlands, d Department of Medical Oncology, Netherlands Cancer Institute-Antony van Leeuwenhoek Hospital, Amsterdam, The Netherlands, e Department of Medical Oncology, Gadjah Mada University, Yogyakarta, Indonesia Background: Epstein-Barr virus (EBV) is causal in WHO-III nasopharyngeal carcinoma (NPC) and 10% of gastric cancers (GC) worldwide. Since all tumour cells carry EBV, the virus itself is a potential target for therapy. However, EBV expresses few non-immunogenic gene products essential for EBV-DNA maintenance and tumour growth. We developed a cytolytic virus activation (CLVA) therapy, reactivating latent EBV into the lytic cycle, triggering immune recognition and inducing susceptibility to antiviral therapy. Methods: CLVA combines a cytostatic drug with valproic acid (VPA) for virus reactivation with (val) ganciclovir (GCV) as an antiviral drug preventing virus replication and killing reactivated tumour cells. CLVA treatment was validated in cell lines and mouse models and in a phase-1/2 clinical trial with Dutch NPC patients refractory to conventional treatment. A similar trial is about to start in Indonesia. Findings: In NPC and GC cell lines, various cytostatic drug combinations induce the EBV lytic cycle, which is enhanced by VPA. Addition of GCV resulted in higher viable cell elimination. CLVA therapy eliminated NPC tumours in nude mice more efficiently and completely than single drugs alone. Using 131FIAU, CLVA responsive tumours in mice could be visualised by PET scan and DNA load in blood, mRNA profiling, and in situ staining confirmed in vivo virus reactivation. A phase 1/2 study with six cycles of CLVA treatment showed that CLVA was well-tolerated in 11 patients with end-stage NPC. Patients showed increased viral DNA in blood with lytic mRNA in nasopharyngeal brushings during treatment. Treatment showed a good response in five patients, two patients developed stable disease and in four patients no (early) effect was seen and therapy was ended. Approval for a phase 1/2 trial for NPC was obtained in Yogyakarta, Indonesia. Interpretation: CLVA successfully activated EBV from latency in NPC and GC tumour cell lines in vitro and cleared NPC tumours from nude mice. In patients, CLVA was well tolerated and showed a biological effect. This new virus-specific CLVA therapy could open a generic approach for treatment of multiple EBV-associated malignancies.
http://dx.doi.org/10.1016/j.ejca.2014.03.170
P0127 CURCUMINOIDS AS PUTATIVE EBV LYTIC INDUCTION AGENTS FOR ADJUVANT TREATMENT IN EBV-POSITIVE CARCINOMA O. Malik a,*, H. Ismail b, G.M. Lin c, H. Timmerman d, J. Middeldorp a. Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands, b Faculty of Pharmacy, Gadjah Mada University, Yogyakarta, Indonesia, c Department of Pharmacy, National University a
http://dx.doi.org/10.1016/j.ejca.2014.03.169
FOR
Abstracts / 50 (2014) e1–e74
of Singapore, Singapore, d Department of Pharmacochemistry, VU University Medical Center, Amsterdam, The Netherlands Background: Epstein-Barr virus (EBV) is causally involved in various lymphoid and non-lymphoid cancers, including nasopharyngeal (NPC) and stomach carcinomas (EBVaGC). NPC is endemic in south east Asia, including Indonesia. EBVaGC accounts for about 10% of GC worldwide. We recently initiated efforts to target EBV inside tumour cells by cytolytic virus activation therapy (CLVA), currently being validated in a phase 1/2 trial. We aim to develop oral drugs to improve CLVA treatment availability for low-income countries. Curcumin (diferuloylmethane) from Curcuma longa is used as spice in Asian countries without any toxic effects and has anti-cancer activity. Several curcumin analogues (curcuminoids), developed to increase efficacy and bioavailability, are currently being tested in clinical studies. Curcuminoids affect multiple pathways, including inhibition of COX2 and NF-kB and have potential as oral CLVA regimens for EBV-positive carcinoma. Methods: We investigated EBV-reactivating effects of curcuminoids on EBV-positive NPC (C666.1) and EBVaGC cell lines (SNU179 and AGS-BX1). EBV-negative GC (AGS) line was used as a negative control. Standard CLVA, SAHA, and bortezomib were used as positive controls. EBV lytic (Zebra, EA-D) activity was measured by semiquantitative immunoblot, FACS and indirect immunofluorescence. Effects on cell viability were measured by MTT assay. Findings: Curcumin induced EBV lytic activity in AGS-BX1 cells but had marginal effect on natural EBV lines (C666.1,SNU179). However, several curcumin analogues induced EBV reactivation in all three EBV-positive cell lines in a dose- and time-dependent manner. MTT assay showed curcuminoids to be more toxic to EBVaGC cells than to C666.1 cells. Noteworthy curcuminoids showed synergistic effects with current lytic induction agents. Interpretation: Curcumin analogues serve as non-toxic drugs to reactivate EBV from latently infected NPC and GC cells, but seem to reactivate EBV differently in NPC versus GC. Curcuminoids at pharmacologically relevant concentrations may promote cytolysis of EBV-positive carcinoma when combined with CLVA drugs. The molecular mechanisms of EBV lytic cycle induction by curcuminoids will be studied to gain further insights in EBV reactivation from latency in different carcinoma models.
http://dx.doi.org/10.1016/j.ejca.2014.03.171
P0128 ASSOCIATION BETWEEN SLC4A7 AND COX11 VARIANTS AND BREAST CANCER IN AN IRANIAN POPULATION V.R. Yassaee a,b, Z. Soltani a, M. Movahedi c . a Genomic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran, b Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran, c Department of Epidemiology, School of Public Health, Evin, Shahid Beheshti University of Medical Sciences, Tehran, Iran Background: Breast cancer is the most common cancer in Iran. An upward trend of breast cancer has been observed in the Iranian population in recent years. Early detection by the molecular approaches may lead to decrease breast cancer morbidity and mortality. Recently two breast cancer susceptibility loci, SLC4A7 (rs4973768) andCOX11 (rs6504950) have been identified. These loci increase the chance of breast cancer development in women up to 6% during their life time. Methods: We used the ARMS method to analyse 543 samples including 407 controls derived from individuals with no clinical signs
e45
of any type of cancer who has been referred to the outpatient clinic at Taleghani hospital, Tehran, and 136 cases who have already been diagnosed with early-onset breast cancer. Findings: In the control group, we found 111 (30.1%) homozygote alleles, 147 (39.8%) heterozygote alleles, and 111 (30.1%) wild-type allele for the rs4973768 marker, and 27 (7.4%) homozygote alleles, 112 (30.5%) heterozygote alleles, and 228 (62.1%) wild-type alleles for rs6504950. The age-adjusted odds ratio for breast cancer in people with homozygote alleles (TT) of the rs4973768 marker was 1.45 (95% confidence interval [CI] 0.81–2.60, p = 0.21) compared with those carrying wild-type of this marker. The odds ratio for people carrying homozygote alleles (AA) of the rs6504950 marker was 5.30 (95% CI 2.75–10.2, p < 0.005) compared with those who were wild-type. Interpretation: Our results are quite different to the data recently reported. There is a significant increased risk of breast cancer in people carrying homozygote (AA) alleles for the COX11 gene and a non-significantly increased risk of breast cancer in people with homozygote (TT) SLC4A7. Further population studies are required to validate these new loci.
http://dx.doi.org/10.1016/j.ejca.2014.03.172
P0129 HEPATITIS C PATIENTS HAVE WORSE OUTCOMES THAN HEPATITIS B PATIENTS FOLLOWING SURGICAL RESECTION FOR HEPATOCELLULAR CARCINOMA BOTH WITHIN AND OUTSIDE OF THE AASLD CRITERIA E. Eu a,*, J. Leong a, J.C. Allen b, B. Haaland b, P.C. Cheow c, A.Y.F. Chung c, L.L.P.J. Ooi c, P.K.H. Chow b,d . a Yong Loo Lin School of Medicine, National University of Singapore, Singapore, b Duke-NUS Graduate Medical School, Singapore, c Department of Hepato-Pancreato-Biliary and Transplant Surgery, SGH, Singapore, d Department of Surgical Oncology, National Cancer Centre Singapore, Singapore Background: Surgery is the mainstay of curative treatment of hepatocellular carcinoma (HCC). The outcomes of resection between patients with hepatitis B (HBV) and hepatitis C (HCV) have been described as being different but previous reports have been difficult to compare as the patients were from different centres. This study aims to determine the differences in surgical outcomes between HBV and HCV patients undergoing surgical resection for HCC at a single institution, by the same group of surgeons using the same operative approach. Methods: We retrospectively studied 679 patients who underwent surgical resection for HCC by the combined HPB Service of the Singapore General Hospital and National Cancer Centre between January 2000 and February 2012. Excluded were patients with positive serology for both HBV and HCV, or negative serology for both. 412 patients fulfilled the study criteria, including 331 patients with single nodule tumours. Findings: Among patients with single nodule tumours (n = 331; i.e., within the AASLD criteria), 295 were positive for HBV and 36 for HCV. Five-year disease-free survival (DFS) was significantly shorter in HCV compared with HBV patients (14.3% versus 36.3%, p = 0.008); a difference was also observed in terms of 5-year overall survival between HCV and HBV (52.0% versus 61.3%, p = 0.42). For the whole cohort (n = 412), the 5-year DFS was also lower in HCV patients than HBV (12.2% versus 33.4%, p = 0.015), and 5-year overall survival was lower in HCV patients than with HBV (45.6% versus 58.4%, p = 0.238).
Abstracts / 50 (2014) e1–e74
Methods: Fifty patients were studied for 36 months. The patients had large volume resections and underwent immediate partial breast reconstruction with lattisimus dorsi flap. Oncological safety was assessed by margin status, and cosmetic outcomes by photographs at 1 month, 3 months, 6 months, and 1 year. Questionnaires were used to evaluate patients’ personal experiences after the reconstruction. Subjective cosmetic assessments were made with LENT–SOMA SCORE. Findings: Patients’ were aged 20–65 years. Surgery was for primary breast cancer in 45 patients, and after neoadjuvant chemotherapy in five. Operating time ranged from 110 to 210 min (mean 153.9 min. Mean blood loss was 134.2 mL (range 75–350). Volume of resection was 30 to 300 cc. The skin island used for volume replacement was 4 cm 3 cm to 14 cm 6 cm. No patients had positive or close margins. Major wound complications occurred in three patients, and minor wound complications in five. Seven patients had seroma and three had lymphoedema. After follow up for 12 to 23 months, 46 patients had scores of 3 or more, while four had a score of less than 3. Interpretation: Oncoplasty is oncologically safe with good cosmetic outcome. Integration of oncoplasty techniques broadens the horizon for breast conservation surgery. Different techniques have to be individually tailored for better results. http://dx.doi.org/10.1016/j.ejca.2014.03.168
P0125 EFFECT OF THE COMBINATION OF FRONDOSIDE A WITH OXALIPLATIN OR FLUOROURACIL IN THE TREATMENT OF COLON CANCER S. Attoub a,*, K. Arafat a, R. Iratni b. a Department of Pharmacology & Therapeutics, College of Medicine & Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates, b Department of Biology, College of Science, United Arab Emirates University, Al-Ain, United Arab Emirates Background: Colorectal cancer is the third leading cause of cancer deaths in the world despite many therapeutic options. We have demonstrated that frondoside A, a triterpenoid glycoside isolated from an Atlantic sea cucumber, has potent in vitro and in vivo anticancer effects against human pancreatic, breast, and lung cancer. We also demonstrated that frondoside A was able to potentiate and/or to synergise the anti-cancer effects of gemcitabine, paclitaxel, and cisplatin in the treatment of pancreatic, breast, and lung cancer, respectively. These results suggest that frondoside A may have an anticancer potential in the treatment of colon cancer either alone, and/or in combination, with the standard cytotoxic drugs oxaliplatin and fluorouracil. Methods: The impact of the treatments on cellular proliferation and apoptosis was determined using cell counter, FACS analysis, and caspase activities. Findings: Frondoside A, oxaliplatin, and fluorouracil induced a concentration-dependent and time-dependent inhibition of cellular proliferation and induced apoptosis in a caspase-dependent manner in the three colorectal cancer cells HT29, HCT116, and HCT8/S11. Combinations of low concentrations of these drugs for 48 h in vitro indicate that frondoside A enhances the inhibition of cell proliferation and the induction of apoptosis mediated by oxaliplatin as well as by fluorouracil. Interpretation: We believe that frondoside A will improve colon cancer therapy in combination with the standard cytotoxic drugs oxaliplatin and fluorouracil.
P0126 CYTOLYTIC VIRUS ACTIVATION THERAPY EPSTEIN-BARR VIRUS DRIVEN TUMOURS
A.E. Greijer a, S.D. Stoker b, Z. Novalic a, O. Malik a, S.A.W.M. Verkuijlen a, H. Juwana a, A.D.R. Huitema c, B.I. Tan b, J.P. de Boer d, S.H. Hutajulu e, J. Kurnianda e, J.M. Middeldorp a,*. a Department of Pathology, VU University Medical Center, Amsterdam, the Netherlands, b Department of Head & Neck Oncology-Surgery, Netherlands Cancer Institute-Antony van Leeuwenhoek Hospital, Amsterdam, The Netherlands, c Department of Pharmacology, Netherlands Cancer Institute-Antony van Leeuwenhoek Hospital, Amsterdam, The Netherlands, d Department of Medical Oncology, Netherlands Cancer Institute-Antony van Leeuwenhoek Hospital, Amsterdam, The Netherlands, e Department of Medical Oncology, Gadjah Mada University, Yogyakarta, Indonesia Background: Epstein-Barr virus (EBV) is causal in WHO-III nasopharyngeal carcinoma (NPC) and 10% of gastric cancers (GC) worldwide. Since all tumour cells carry EBV, the virus itself is a potential target for therapy. However, EBV expresses few non-immunogenic gene products essential for EBV-DNA maintenance and tumour growth. We developed a cytolytic virus activation (CLVA) therapy, reactivating latent EBV into the lytic cycle, triggering immune recognition and inducing susceptibility to antiviral therapy. Methods: CLVA combines a cytostatic drug with valproic acid (VPA) for virus reactivation with (val) ganciclovir (GCV) as an antiviral drug preventing virus replication and killing reactivated tumour cells. CLVA treatment was validated in cell lines and mouse models and in a phase-1/2 clinical trial with Dutch NPC patients refractory to conventional treatment. A similar trial is about to start in Indonesia. Findings: In NPC and GC cell lines, various cytostatic drug combinations induce the EBV lytic cycle, which is enhanced by VPA. Addition of GCV resulted in higher viable cell elimination. CLVA therapy eliminated NPC tumours in nude mice more efficiently and completely than single drugs alone. Using 131FIAU, CLVA responsive tumours in mice could be visualised by PET scan and DNA load in blood, mRNA profiling, and in situ staining confirmed in vivo virus reactivation. A phase 1/2 study with six cycles of CLVA treatment showed that CLVA was well-tolerated in 11 patients with end-stage NPC. Patients showed increased viral DNA in blood with lytic mRNA in nasopharyngeal brushings during treatment. Treatment showed a good response in five patients, two patients developed stable disease and in four patients no (early) effect was seen and therapy was ended. Approval for a phase 1/2 trial for NPC was obtained in Yogyakarta, Indonesia. Interpretation: CLVA successfully activated EBV from latency in NPC and GC tumour cell lines in vitro and cleared NPC tumours from nude mice. In patients, CLVA was well tolerated and showed a biological effect. This new virus-specific CLVA therapy could open a generic approach for treatment of multiple EBV-associated malignancies.
http://dx.doi.org/10.1016/j.ejca.2014.03.170
P0127 CURCUMINOIDS AS PUTATIVE EBV LYTIC INDUCTION AGENTS FOR ADJUVANT TREATMENT IN EBV-POSITIVE CARCINOMA O. Malik a,*, H. Ismail b, G.M. Lin c, H. Timmerman d, J. Middeldorp a. Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands, b Faculty of Pharmacy, Gadjah Mada University, Yogyakarta, Indonesia, c Department of Pharmacy, National University a
http://dx.doi.org/10.1016/j.ejca.2014.03.169
FOR
Abstracts / 50 (2014) e1–e74
of Singapore, Singapore, d Department of Pharmacochemistry, VU University Medical Center, Amsterdam, The Netherlands Background: Epstein-Barr virus (EBV) is causally involved in various lymphoid and non-lymphoid cancers, including nasopharyngeal (NPC) and stomach carcinomas (EBVaGC). NPC is endemic in south east Asia, including Indonesia. EBVaGC accounts for about 10% of GC worldwide. We recently initiated efforts to target EBV inside tumour cells by cytolytic virus activation therapy (CLVA), currently being validated in a phase 1/2 trial. We aim to develop oral drugs to improve CLVA treatment availability for low-income countries. Curcumin (diferuloylmethane) from Curcuma longa is used as spice in Asian countries without any toxic effects and has anti-cancer activity. Several curcumin analogues (curcuminoids), developed to increase efficacy and bioavailability, are currently being tested in clinical studies. Curcuminoids affect multiple pathways, including inhibition of COX2 and NF-kB and have potential as oral CLVA regimens for EBV-positive carcinoma. Methods: We investigated EBV-reactivating effects of curcuminoids on EBV-positive NPC (C666.1) and EBVaGC cell lines (SNU179 and AGS-BX1). EBV-negative GC (AGS) line was used as a negative control. Standard CLVA, SAHA, and bortezomib were used as positive controls. EBV lytic (Zebra, EA-D) activity was measured by semiquantitative immunoblot, FACS and indirect immunofluorescence. Effects on cell viability were measured by MTT assay. Findings: Curcumin induced EBV lytic activity in AGS-BX1 cells but had marginal effect on natural EBV lines (C666.1,SNU179). However, several curcumin analogues induced EBV reactivation in all three EBV-positive cell lines in a dose- and time-dependent manner. MTT assay showed curcuminoids to be more toxic to EBVaGC cells than to C666.1 cells. Noteworthy curcuminoids showed synergistic effects with current lytic induction agents. Interpretation: Curcumin analogues serve as non-toxic drugs to reactivate EBV from latently infected NPC and GC cells, but seem to reactivate EBV differently in NPC versus GC. Curcuminoids at pharmacologically relevant concentrations may promote cytolysis of EBV-positive carcinoma when combined with CLVA drugs. The molecular mechanisms of EBV lytic cycle induction by curcuminoids will be studied to gain further insights in EBV reactivation from latency in different carcinoma models.
http://dx.doi.org/10.1016/j.ejca.2014.03.171
P0128 ASSOCIATION BETWEEN SLC4A7 AND COX11 VARIANTS AND BREAST CANCER IN AN IRANIAN POPULATION V.R. Yassaee a,b, Z. Soltani a, M. Movahedi c . a Genomic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran, b Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran, c Department of Epidemiology, School of Public Health, Evin, Shahid Beheshti University of Medical Sciences, Tehran, Iran Background: Breast cancer is the most common cancer in Iran. An upward trend of breast cancer has been observed in the Iranian population in recent years. Early detection by the molecular approaches may lead to decrease breast cancer morbidity and mortality. Recently two breast cancer susceptibility loci, SLC4A7 (rs4973768) andCOX11 (rs6504950) have been identified. These loci increase the chance of breast cancer development in women up to 6% during their life time. Methods: We used the ARMS method to analyse 543 samples including 407 controls derived from individuals with no clinical signs
e45
of any type of cancer who has been referred to the outpatient clinic at Taleghani hospital, Tehran, and 136 cases who have already been diagnosed with early-onset breast cancer. Findings: In the control group, we found 111 (30.1%) homozygote alleles, 147 (39.8%) heterozygote alleles, and 111 (30.1%) wild-type allele for the rs4973768 marker, and 27 (7.4%) homozygote alleles, 112 (30.5%) heterozygote alleles, and 228 (62.1%) wild-type alleles for rs6504950. The age-adjusted odds ratio for breast cancer in people with homozygote alleles (TT) of the rs4973768 marker was 1.45 (95% confidence interval [CI] 0.81–2.60, p = 0.21) compared with those carrying wild-type of this marker. The odds ratio for people carrying homozygote alleles (AA) of the rs6504950 marker was 5.30 (95% CI 2.75–10.2, p < 0.005) compared with those who were wild-type. Interpretation: Our results are quite different to the data recently reported. There is a significant increased risk of breast cancer in people carrying homozygote (AA) alleles for the COX11 gene and a non-significantly increased risk of breast cancer in people with homozygote (TT) SLC4A7. Further population studies are required to validate these new loci.
http://dx.doi.org/10.1016/j.ejca.2014.03.172
P0129 HEPATITIS C PATIENTS HAVE WORSE OUTCOMES THAN HEPATITIS B PATIENTS FOLLOWING SURGICAL RESECTION FOR HEPATOCELLULAR CARCINOMA BOTH WITHIN AND OUTSIDE OF THE AASLD CRITERIA E. Eu a,*, J. Leong a, J.C. Allen b, B. Haaland b, P.C. Cheow c, A.Y.F. Chung c, L.L.P.J. Ooi c, P.K.H. Chow b,d . a Yong Loo Lin School of Medicine, National University of Singapore, Singapore, b Duke-NUS Graduate Medical School, Singapore, c Department of Hepato-Pancreato-Biliary and Transplant Surgery, SGH, Singapore, d Department of Surgical Oncology, National Cancer Centre Singapore, Singapore Background: Surgery is the mainstay of curative treatment of hepatocellular carcinoma (HCC). The outcomes of resection between patients with hepatitis B (HBV) and hepatitis C (HCV) have been described as being different but previous reports have been difficult to compare as the patients were from different centres. This study aims to determine the differences in surgical outcomes between HBV and HCV patients undergoing surgical resection for HCC at a single institution, by the same group of surgeons using the same operative approach. Methods: We retrospectively studied 679 patients who underwent surgical resection for HCC by the combined HPB Service of the Singapore General Hospital and National Cancer Centre between January 2000 and February 2012. Excluded were patients with positive serology for both HBV and HCV, or negative serology for both. 412 patients fulfilled the study criteria, including 331 patients with single nodule tumours. Findings: Among patients with single nodule tumours (n = 331; i.e., within the AASLD criteria), 295 were positive for HBV and 36 for HCV. Five-year disease-free survival (DFS) was significantly shorter in HCV compared with HBV patients (14.3% versus 36.3%, p = 0.008); a difference was also observed in terms of 5-year overall survival between HCV and HBV (52.0% versus 61.3%, p = 0.42). For the whole cohort (n = 412), the 5-year DFS was also lower in HCV patients than HBV (12.2% versus 33.4%, p = 0.015), and 5-year overall survival was lower in HCV patients than with HBV (45.6% versus 58.4%, p = 0.238).