Background/Purpose : A recent genome-wide association study (PanScan) identified significant association between the ABO gene locus and the risk of pancreatic cancer. The aim of this study was to analyze survival of pancreatic cancer patients who underwent surgical resection based on serotype-defined ABO blood types. Methods : In terms of ABO blood types and gemcitabine-based adjuvant therapy, we investigated the survival of 153 patients who underwent pancreatectomy for pancreatic cancer at the Department of Surgery and Oncology,KyushuUniversity(Fukuoka,Japan). Results : Among the four blood type groups, the O serotype group (median survival time (MST): 47 . 9 months) showed the best prognostic outcome. The A serotype group (MST: 22 . 5 months) showed the second best prognostic outcome, followed by the AB serotype group (MST: 20 . 4 months). The B serotype group (MST: 15 months) showed the worst prognostic outcome when considering the MST after the surgical resection. Next, we examined the effect of adjuvant chemotherapy with gemcitabine based on the ABO blood types. The A serotype group showed the greatest improvement in prognosis by adjuvant therapy with gemcitabine after the surgical resection. The other three serotype groups showed no significant differences in the prognostic outcomes between subgroups with and without gemcitabine therapy. Conclusions : The present data suggest the possibility that ABO blood types are prognostic factors for pancreatic cancer patients after surgical treatment and are also predictive factors for the chemosensitivity to gemcitabine of pancreatic cancer patients after pancreatectomy.
A. Jemal, R. Siegel, E. Ward, Y. Hao, J. Xu and M. J. Thun, “Cancer Statistics,” Cancer Journal for Clinicians, Vol. 59, No. 4, 2009, pp. 225-249. http://dx.doi.org/10.3322/caac.20006
A. L. Warshaw and C. Fernandez-del Castillo, “Pancreatic carcinoma,” The New England Journal of Medicine, Vol. 326, No. 7, 1992, pp. 455-465. http://dx.doi.org/10.1056/NEJM199202133260706
H. A. Burris, M. J. Moore, J. Andersen, et al., “Improvements in Survival and Clinical Benefit with Gemcitabine as First-Line Therapy for Patients with Advanced Pancreas Cancer: A Randomized Trial,” Journal of Clinical Oncology, Vol. 15, No. 6, 1997, pp. 2403-1413.
D. Li, K. Xie, R .Wolff and J. L. Abbruzzese, “Pancreatic Cancer,” Lancet, Vol. 363, No. 9414, 2004, pp. 10491057. http://dx.doi.org/10.1016/S0140-6736(04)15841-8
B. M. Wolpin, P. Kraft, M. Gross, et al., “Pancreatic Cancer Risk and ABO Blood Group Alleles: Results from the pancreatic Cancer Cohort Consortium,” Cancer Research, Vol. 70, No. 3, 2010, pp. 1015-1023. http://dx.doi.org/10.1158/0008-5472.CAN-09-2993
N. Kurata, H. Fujita, K. Ohuchida, et al., “Predicting the Chemosensitivity of Pancreatic Cancer Cells by Quantifying the Expression Levels of Genes Associated with the Metabolism of Gemcitabine and 5-Fluorouracil,” International Journal of Oncology, Vol. 39, No. 2, 2011, pp. 473-482.
A. K. Fukunaga, S. Marsh, D. J. Murry, T. D. Hurley and H. L. McLeod, “Identification and Analysis of Single-Nucleotide Polymorphisms in the Gemcitabine Pharmacologic Pathway,” The Pharmacogenomics Journal, Vol. 4, No. 5, 2004, pp. 307-314. http://dx.doi.org/10.1038/sj.tpj. 6500259
A. W. Blackstock, H. Lightfoot, L. D. Case, et al., “Tumor Uptake and Elimination of 2’,2’-Difluoro-2’-Deoxycytidine (Gemcitabine) after Deoxycytidine Kinase Gene Transfer: Correlation with in Vivo Tumor Response,” Clinical Cancer Research, Vol. 7, No. 10, 2001, pp. 3263-3268.
M. S. Duxbury, H. Ito, M. J. Zinner, S. W. Ashley and E. E. Whang, “RNA Interference Targeting the M2 Subunit of Ribonucleotide Reductase Enhances Pancreatic Adenocarcinoma Chemosensitivity to Gemcitabine,” Oncogene, Vol. 23, No. 8, 2004, pp. 1539-1548. http://dx.doi.org/10.1038/sj.onc. 1207272
H. Fujita, K. Ohuchida, K. Mizumoto, et al., “Gene Expression Levels as Predictive Markers of Outcome in Pancreatic Cancer after Gemcitabine-Based Adjuvant Chemotherapy,” Neoplasia, Vol. 12, No. 10, 2010, pp. 807-817.
S. Ohhashi, K. Ohuchida, K. Mizumoto, et al., “DownRegulation of Deoxycytidine Kinase Enhances Acquired Resistance to Gemcitabine in Pancreatic Cancer,” Anticancer Research, Vol. 28, No. 4B, 2008, pp. 2205-2212.
E. Giovannetti, M. Del Tacca, V. Mey, et al., “Transcription Analysis of Human Equilibrative Nucleoside Transporter-1 Predicts Survival in Pancreas Cancer Patients Treated with Gemcitabine,” Cancer Research, Vol. 66, No. 7, 2006, pp. 3928-3935. http://dx.doi.org/10.1158/0008-5472.CAN-05-4203
J. Spratlin, R. Sangha, D. Glubrecht, et al., “The Absence of Human Equilibrative Nucleoside Transporter 1 is Associated with Reduced Survival in Patients with Gemcitabine-Treated Pancreas Adenocarcinoma,” Clinical Cancer Research, Vol. 10, No. 20, 2004, pp. 6956-6961. http://dx.doi.org/10.1158/1078-0432.CCR-04-0224
Q. Ben, K. Wang, Y. Yuan and Z. Li, “Pancreatic Cancer Incidence and Outcome in Relation to ABO Blood Groups among Han Chinese Patients: A Case-Control Study,” International Journal of Cancer, Vol. 128, No. 5, 2011, pp. 1179-1186. http://dx.doi.org/10.1002/ijc.25426
S. Hakomori, “Antigen Structure and Genetic Basis of Histo-Blood Groups A, B and O: Their Changes Associated with Human Cancer,” Biochimica et Biophysica Acta, Vol. 1473, No. 1, 1999, pp. 247-266. http://dx.doi.org/10.1016/S0304-4165(99)00183-X
M. E. Reid and N. Mohandas, “Red Blood Cell Blood Group Antigens: Structure and Function,” Seminars in Hematology, Vol. 41, No. 2, 2004, pp. 93-117. http://dx.doi.org/10.1053/j.seminhematol. 2004.01.001
I. Aird, H. H. Bentall, J. A. Roberts, “A Relationship between Cancer of Stomach and the ABO Blood Groups,” British Medical Journal, Vol. 1, No. 4814, 1953, pp. 799-801. http://dx.doi.org/10.1136/bmj. 1.4814.799
G. Edgren, H. Hjalgrim, K. Rostgaard, et al., “Risk of Gastric Cancer and Peptic Ulcers in Relation to ABO Blood Type: A Cohort Study,” American Journal of Epidemiology, Vol. 172, No. 11, 2010, pp. 1280-1285. http://dx.doi.org/10.1093/aje/kwq299
M. A. Gates, B. M. Wolpin, D. W. Cramer, S. E. Hankinson and S. S. Tworoger, “ABO Blood Group and Incidence of Epithelial Ovarian Cancer,” International Journal of Cancer, Vol. 128, No. 2, 2010, pp. 482-486. http://dx.doi.org/10.1002/ijc.25339
S. H. Itzkowitz, M. Yuan, L. D. Ferrell, et al., “Cancer-Associated Alterations of Blood Group Antigen Expression in the Human Pancreas,” Journal of the National Cancer Institute, Vol. 79, No. 3, 1987, pp. 425-434.
E. Uchida, M. A. Tempero, D. A. Burnett, Z. Steplewski, P. M. Pour, “Correlative Studies on Antigenicity of Pancreatic Cancer and Blood Group Types,” Cancer Detection and Prevention, Vol. 1, No., 1987, pp. 145-148.
P. M. Pour, M. M. Tempero, H. Takasaki, et al., “Expression of Blood Group-Related Antigens ABH, Lewis A, Lewis B, Lewis X, Lewis Y, and CA 19-9 in Pancreatic Cancer Cells in Comparison with the Patient’s Blood Group Type,” Cancer Research, Vol. 48, No. 19, 1988, pp. 5422-5426.
M. H. Schuessler, S. Pintado, S. Welt, et al., “Blood Group and Blood-Group-Related Antigens in Normal Pancreas and Pancreas Cancer: Enhanced Expression of Precursor Type 1, Tn and Sialyl-Tn in Pancreas Cancer,” International Journal of Cancer, Vol. 47, No. 2, 1991, pp. 180-187. http://dx.doi.org/10.1002/ijc.2910470204
S. Zhang, H. S. Zhang, C. Cordon-Cardo, et al., “Selection of Tumor Antigens as Targets for Immune Attack Using Immunohistochemistry: II. Blood Group-Related Antigens,” International Journal of Cancer, Vol. 73, No. 1, 1997, pp. 50-56. http://dx.doi.org/10.1002/(SICI)1097-0215(19970926) 73:1 3.3.CO;2-O
S. Hakomori, “Tumor-Associated Carbohydrate Antigens Defining Tumor Malignancy: Basis for Development of Anti-Cancer Vaccines,” Advances in Experimental Medicine and Biology, Vol. 491, 2001, pp. 369-402. http://dx.doi.org/10.1007/978-1-4615-1267-7_24