Journal of Cancer Therapy, 2013, 4, 7-12
Published Online November 2013 (http://www.scirp.org/journal/jct)
http://dx.doi.org/10.4236/jct.2013.410A002
Open Access JCT
7
Impact of ABO Blood Types on Survival after
Pancreatectomy for Pancreatic Cancer*
Tadashi Kayashima1, Masafumi Nakamura1, Kenoki Ohuchida1,2, Syunichi Takahata1, Kohei Nakata1,
Naoki Ikenaga1, Lin Cui1, Shingo Kozono1, Kazuhiro Mizumoto1,3, Masao Tanaka1#
1Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; 2Department of
Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; 3Kyushu University Hos-
pital Cancer Center, Fukuoka, Japan.
Received July 18th, 2013; revised August 17th, 2013; accepted August 25th, 2013
Copyright © 2013 Tadashi Kayashima et al. This is an open access article distributed under the Creative Commons Attribution Li-
cense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ABSTRACT
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 can-
cer 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 pan-
createctomy for pancreatic cancer at the Department of Surgery and Oncology, Kyushu University (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 improve-
ment in prognosis by adjuvant therapy with gemcitabine after the surgical resection. The other three serotype groups
showed no significant differ ences in the prognostic outcomes between subgroups with and without g emcitabine therapy.
Conclusions: The present data suggest the possibility that ABO blood types are prognostic factor s fo r pancreatic cancer
patients after surgical treatment and are also predictive factors for the chemosensitivity to gemcitabine of pancreatic
cancer patients after pancreatectomy.
Keywords: Pancreatic Cancer; ABO Blood Type; Survival; Gemcitabine; Adjuvant Chemotherapy
1. Introduction
Pancreatic cancer is the fourth leading cause of cancer-
related death in the United States, and has the lowest
survival rate for any solid tumo r [1,2]. Owing to a lack of
early detection methods and an absence of effective bio-
markers, patients are usually diagnosed at late stages
with a 5-year survival rate of <5% [1]. The first-line
agent gemcitabine produces some clinical benefit in the
advanced setting, but yields limited disease control, with
<15% of patients remaining progression-free at 6 months
after diagnosis [3,4].
For several decades, roles of the ABO blood group an-
tigens have been suspected in the development of certain
malignancies. A recent genome-wide association study
(PanScan) identified significant association of the ABO
gene locus with the risk of pancreatic cancer, but the in-
fluence of the specific ABO serotypes remains unknown
[5].
To date, there are some studies that have investigated
the correlations between certain gene expression levels
and chemosensitivity to g emcitabine in pancreatic cancer
patients [6-13]. However, to our knowledge, there are no
reports regarding the relationships between chemosensi-
tivity and ABO blood types in pancreatic cancer after
surgical resection.
*Supported in part by a Grant-in-Aid from the Ministry of Education,
Culture, Sports, Science and Technology of Japan. The current address
of Masafumi Nakamura is Department of Digestive Surgery, Kawasaki
Medical School, Kurashiki, Japan.
#Corresponding author.

Impact of ABO Blood Types on Survival after Pancreatectomy for Pancreatic Cancer 8
In the present study, we analyzed the survival and ef-
fects of gemcitabine based on serotype-defined ABO
blood types in 153 patients who underwent surgical re-
section at the Department of Surgery and Oncology,
Kyushu University (Fukuoka, Japan). Our data suggest
that the O serotype is associated with significantly longer
survival of the patients than other ABO blood groups and
that the A serotype is correlated with better effects of
gemcitabine on survival of the patients after surgical re-
section.
2. Methods
2.1. Patients
The medical records of 153 patients who underwent sur-
gical resection for pancreatic cancer at the Department of
Surgery and Oncology, Kyushu University (Fukuoka,
Japan), between 27 January 1992 and 19 March 2010
were retrospectively reviewed. The ABO blood types
were as follows: A serotype, 75 patients; O serotype, 33
patients; B serotype, 26 patients; AB serotype, 19 pa-
tients. The characteristics of the patients are shown in
Table 1.
2.2. Statistical Analysis
All statistical analyses were carried out using JMP 8.0.1
software (SAS Institute, Cary, NC). Survival curv es were
calculated by the Kaplan-Meier method, and differences
between the curves were analyzed by the log-rank test.
All differences were considered to be statistically sig-
nificant for values of P < 0.05.
3. Results
3.1. Survival Curves Based on the ABO
Blood types
The survival curves based on the serotype-defined ABO
blood types are shown in Figure 1(a). The respective
5-year survival rate and median survival time (MST) for
each of the four serotype groups were as follows: O se-
rotype group, 47.1% and 47.9 months; A serotype group,
22.6% and 22.5 months; AB serotype group, 0% and
20.4 months; and B serotype group, 25.2% and 15
months.
In a comparison of the prognoses in the O serotype
group and a combined non-O serotype group, the 5-year
survival rate and MST in the O serotype group (47.1%
and 47.9 months, respectively) were significantly higher
and longer, respectively, than those in the non-O sero-
type group (20.5% and 22.5 months, respectively; P =
0.0276, log-rank test) (Figure 1(b)).
There was no distance by R0/R1, 2 (P = 0.790 Chi-
square test), and with radiotherapy (post or preoperative)
or without radiotherapy (P = 0.152 Chi-square test), op-
erative method (DP/PD and PpPD/TP, P = 0.930 Chi-
square test), staging according UICC TNM (0 ~ II/III ~
IV, P = 0.105 Chi-square test), but there was significant
difference by lymph nod es negative or p ositive (P < 0.01
Chi-square test).
In addition, the median disease-free survival time and
5-year disease-free survival rate in the serotype O group
tended to be longer and higher, respectively, than those
in the non-O serotyp e group (Figure 1(c); mean disease-
free survival time: 42 months vs. 14.5 months; 5-year
disease-free survival rate: 10.6% vs. 7.3%; P = 0.066,
log-rank test), but there was no significant difference.
3.2. Effects of Gemcitabine Adjuvant
Chemotherapy Based on ABO Blood Types
Next, we compared the effect of chemotherapy with
gemcitabine on survival of the pancreatic cancer patients
among the ABO blood type groups. Two patients in the
A serotype group were excluded from the analysis be-
cause their treatments after the surgical resection were
unknown. Consequently, 151 patients were analyzed for
their survival (Table 1). The A serotype group showed
Table 1. Characteristics of the patients based on the serotype-defined ABO blood types.
Characteristic Serologic-derived ABO blood type
O A AB B
No. of patients 33 75 19 26
Mean age 63.5 ± 10.3 64.2 ± 10.5 64.1 ± 7.6 69.9 ± 7.4
Female gender (%) 36.4% 38.2% 21.1% 30.8%
Staging according to UICC TNM (0 ~ II/III ~ IV) 32/1 71/5 18/1 23/3
With Gemcitabine treatment after the surgical resection 21 37 10 15
Mean age 65 ± 9.3 61.8 ± 10.9 62.1 ± 8.3 70.7 ± 7.3
Female gender (%) 33.3% 37.8% 30% 26.7%
Staging according to UICC TNM (0 ~ II/III ~ IV) 21/0 34/3 9/1 13/2
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Impact of ABO Blood Types on Survival after Pancreatectomy for Pancreatic Cancer 9
(a) (b)
(c)
Figure 1. Survival curves based on the ABO blood serotypes of pancreatic cancer patients after surgical resection. (a) Sur-
vival curves based on the ABO blood serotypes. Among the four blood serotypes, the O serotype group showed the best
prognostic outcome after surgical resection of pancreatic cancer (n = 33; 5-year survival rate: 47.1%; MST: 47.9 months).
The A serotype group showed the second best prognostic outcome (n = 75; 5-year survival rate: 22.6%; MST: 22.5 months),
followed by the AB sero type group (n = 19; 5-year survival rate: 0%; MST: 20.4 months). The B serotype group showed the
worst prognostic outcome (n = 26; 5-year survival rate: 25.2%; MST: 15 months) when considering the MST after the surgi-
cal resection. (b) Survival curves based on the O serotype group and a combined non-O serotype group. The MST and 5-year
survival rate were significantly longer and higher, respectively, in the O serotype group (n = 33) than in the non-O serotype
group (n = 120) (MST: 47.9 months vs. 22.5 months; 5-year survival rate: 47.1% vs. 20.5%; P = 0.0276, log-rank test). (c)
Disease-free survival curves based on the O serotype group and the non-O serotype group. The median disease-free survival
time and 5-year disease-free survival rate also tended to be longer and higher, respectively, in the O serotype group than in
the non-O serotype group (mean disease-free survival time: 42 months vs. 14.5 months; 5-year disease-free survival rate:
10.6% vs. 7.3%; P = 0.066, log-rank test), but the difference was not significant.
the greatest effect of gemcitabine treatment (Figure 2(a);
gemcitabine treatment group (n = 37) vs. no gemcitabine
treatment group (n = 36), 5-year survival rate: 39.7% vs.
9.6%; MST: 30.5 months vs. 10.4 months; P = 0.002).
The other three serotype groups showed no significant
differences in the progno sis between subgroups with and
without gemcitabine treatment (Figure 2(b)-(d)).
4. Discussion
In the present study, we found that the MST and 5-year
survival rate of the O serotype group of patients after
pancreatic cancer resection were significantly longer and
higher, respectively, than those in the other serotype
groups, and that adjuvant gemcitabine therapy for pan-
creatic cancer was more effective for the A serotype
group of the patients compared with the other serotype
groups.
Consistent with our findings, PanScan, a recent ge-
nome-wide association study, identified significant asso-
ciations between the ABO gene locus and the risk of
pancreatic cancer [5]. In addition, another recent study of
patients who underwent a potentially curative operation
in China showed that the mean survival time of patients
with blood group O was significantly longer than that of
patients with non-O blood groups (16.0 months vs. 11.0
months, respectively, P = 0.001, log-rank test) [14].
Their study showed an evidence of an association be-
tween blood groups and the risk of the development and
progression of pancreatic cancer. However, the MSTs of
their patients with O and non-O blood groups were much
shorter than those of our patients. The exact reason for
these differences remains unknown.
The ABO human blood group antigens are glycopro-
teins expressed on the surface of red blood cells and the
cells in several other tissue types. For example, th e ABO
antigens are high ly expressed on the surface of epithelial
cells in the gastrointestinal, bronchopulmonary, and uro-
genital tracts [15,16]. Taking our findings and the previ-
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Impact of ABO Blood Types on Survival after Pancreatectomy for Pancreatic Cancer 10
(a) (b)
(c) (d)
Figure 2. Survival of pancreatic cancer patients after surgical resection with and without adjuvant gemcitabine chemother-
apy based on the ABO blood seroty pes. (a) Survival c urves base d on subgr oups w ith and wi thout gemcitabine treatment after
surgical resection in the A serotype group (gemcitabine treatment group: n = 37, 5-year survival rate: 39.7%, MST: 30.5
months; no gemcitabine treatment gr oup: n = 36, 5-year survival rate: 9.6%, MST: 10.4 months; P = 0.0002, log-rank test). (b)
Survival curves based on subgroups with and without gemcitabine treatment after surgical resection in the O serotype group
(gemcitabine treatment gr oup: n = 21, 5-year survival rate: 50.8%, MST: 62.1 months; no gemcitabine treatment group: n =
12, 5-year survival rate: 40%, MST: 39.8 months; P = 0.41, log-rank test). (c) Survival curves based on subgroups with and
without gemcitabine treatment after surgical resection in the AB serotype group (gemcitabine treatment group: n = 10,
5-year survival rate: 0%, MST: 20.4 months; no gemcitabine treatment group: n = 9, 5-year survival rate: 0%, MST: 17.5
months; P = 0.71, log-rank test). (d) Survival curves based on subgroups with and without gemcitabine treatment after sur-
gical resection in the B serotype group (gemcitabine treatment group: n = 15, 5-year survival rate: 0%, MST: 13.1 months;
no gemcitabine treatment group: n = 11, 5-year survival rate: 19.9%, MST: 15 months; P = 0.46, log-rank test).
ously published observations together, it is possible that
the blood type antigens have some roles in oncogenesis
and cancer progression in digestive organs. Indeed, an
association between blood type A and the incidence of
gastric cancer was previously reported [17,18]. Interest-
ingly, the presence of the B antigen was reported to be
positively associated with the incidence of ovarian cancer,
whereas blood group A was not associated with this risk
[19].
When we focus on the pancreas, previous pathological
studies demonstrated the deletion and novel expression
of the A, B, and H antigens on the surface of pancreatic
cancer cells compared with the surrounding normal duc-
tal cells [20-23]. It has also been suggested that modifi-
cations of the glycosyltransferase specificity occur dur-
ing pancreatic tumorigenesis [5]. Glycosyltransferases
are cell surface molecules that are recognized by the host
immune response and may have a role in facilitating
immunosurveillance for malignant cells [24,25].
The detailed mechanism connecting the prognosis of
pancreatic cancer patients and the ABO blood types re-
mains unknown in the present study. Further explorations
of the detailed mechanism may lead to the development
of completely new cancer treatments. The mechanism
underlying the relationship between blood type A and the
effects of gemcitabine adjuvant chemotherapy of pancre-
atic cancer clearly demonstrated in the present study is
also important to overcome the drug tolerance of pancre-
atic cancer. Further investigations are necessary to eluci-
date the mechanisms underlying the findings obtained in
this study.
5. Acknowledgements
We thank Midori Kojyo, Makiko Masuda, and Masayo
Matsuzaki (Department of Surgery and Oncology, Kyu-
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Impact of ABO Blood Types on Survival after Pancreatectomy for Pancreatic Cancer 11
shu University) for their secretarial assistance, and the
Research Support Center, Graduate School of Medical
Sciences, Kyushu University for their technical support.
REFERENCES
[1] 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
[2] A. L. Warshaw and C. Fernandez-del Castillo, “Pan-
creatic carcinoma,” The New England Journal of Medi-
cine, Vol. 326, No. 7, 1992, pp. 455-465.
http://dx.doi.org/10.1056/NEJM199202133260706
[3] H. A. Burris, M. J. Moore, J. Andersen, et al., “Improve-
ments in Survival and Clinical Benefit with Gemcitabine
as First-Line Therapy for Patients with Advanced Pan-
creas Cancer: A Randomized Trial,” Journal of Clinical
Oncology, Vol. 15, No. 6, 1997, pp. 2403-1413.
[4] D. Li, K. Xie, R .Wolff and J. L. Abbruzzese, “Pancreatic
Cancer,” Lancet, Vol. 363, No. 9414, 2004, pp. 1049-
1057. http://dx.doi.org/10.1016/S0140-6736(04)15841-8
[5] B. M. Wolpin, P. Kraft, M. Gross, et al., “Pancreatic Can-
cer 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
[6] N. Kurata, H. Fujita, K. Ohuchida, et al., “Predicting the
Chemosensitivity of Pancreatic Cancer Cells by Quanti-
fying the Expression Levels of Genes Associated with the
Metabolism of Gemcitabine and 5-Fluorouracil,” Interna-
tional Journal of Oncology, Vol. 39, No. 2, 2011, pp.
473-482.
[7] A. K. Fukunaga, S. Marsh, D. J. Murry, T. D. Hurley and
H. L. McLeod, “Identification and Analysis of Sin-
gle-Nucleotide Polymorphisms in the Gemcitabine Phar-
macologic Pathway,” The Pharmacogenomics Journal,
Vol. 4, No. 5, 2004, pp. 307-314.
http://dx.doi.org/10.1038/sj.tpj.6500259
[8] A. W. Blackstock, H. Lightfoot, L. D. Case, et al., “Tu-
mor Uptake and Elimination of 2’,2’-Difluoro-2’-Deoxy-
cytidine (Gemcitabine) after Deoxycytidine Kinase Gene
Transfer: Correlation with in Vivo Tumor Response,”
Clinical Cancer Research, Vol. 7, No. 10, 2001, pp.
3263-3268.
[9] 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 Ade-
nocarcinoma Chemosensitivity to Gemcitabine,” Onco-
gene, Vol. 23, No. 8, 2004, pp. 1539-1548.
http://dx.doi.org/10.1038/sj.onc.1207272
[10] H. Fujita, K. Ohuchida, K. Mizumoto, et al., “Gene Ex-
pression Levels as Predictive Markers of Outcome in Pan-
creatic Cancer after Gemcitabine-Based Adjuvant Che-
motherapy,” Neoplasia, Vol. 12, No. 10, 2010, pp. 807-
817.
[11] S. Ohhashi, K. Ohuchida, K. Mizumoto, et al., “Down-
Regulation of Deoxycytidine Kinase Enhances Acquired
Resistance to Gemcitabine in Pancreatic Cancer,” Anti-
cancer Research, Vol. 28, No. 4B, 2008, pp. 2205-2212.
[12] E. Giovannetti, M. Del Tacca, V. Mey, et al., “Transcrip-
tion Analysis of Human Equilibrative Nucleoside Trans-
porter-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
[13] J. Spratlin, R. Sangha, D. Glubrecht, et al., “The Absence
of Human Equilibrative Nucleoside Transporter 1 is As-
sociated with Reduced Survival in Patients with Gemcit-
abine-Treated Pancreas Adenocarcinoma,” Clinical Can-
cer Research, Vol. 10, No. 20, 2004, pp. 6956-6961.
http://dx.doi.org/10.1158/1078-0432.CCR-04-0224
[14] 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
[15] S. Hakomori, “Antigen Structure and Genetic Basis of
Histo-Blood Groups A, B and O: Their Changes Associ-
ated 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
[16] 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
[17] 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
[18] 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 Epi-
demiology, Vol. 172, No. 11, 2010, pp. 1280-1285.
http://dx.doi.org/10.1093/aje/kwq299
[19] M. A. Gates, B. M. Wolpin, D. W. Cramer, S. E. Han-
kinson and S. S. Tworoger, “ABO Blood Group and In-
cidence of Epithelial Ovarian Cancer,” International
Journal of Cancer, Vol. 128, No. 2, 2010, pp. 482-486.
http://dx.doi.org/10.1002/ijc.25339
[20] S. H. Itzkowitz, M. Yuan, L. D. Ferrell, et al., “Can-
cer-Associated Alterations of Blood Group Antigen Ex-
pression in the Human Pancreas,” Journal of the National
Cancer Institute, Vol. 79, No. 3, 1987, pp. 425-434.
[21] E. Uchida, M. A. Tempero, D. A. Burnett, Z. Steplewski,
P. M. Pour, “Correlative Studies on Antigenicity of Pan-
creatic Cancer and Blood Group Types,” Cancer Detec-
tion and Prevention, Vol. 1, No., 1987, pp. 145-148.
[22] P. M. Pour, M. M. Tempero, H. Takasa ki, et al., “Expres-
sion 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.
[23] 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
Open Access JCT

Impact of ABO Blood Types on Survival after Pancreatectomy for Pancreatic Cancer
Open Access JCT
12
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
[24] S. Zhang, H. S. Zhang, C. Cordon-Cardo, et al., “Selec-
tion 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<50::AID-IJC9>3.3.CO;2-O
[25] S. Hakomori, “Tumor-Associated Carbohydrate Antigens
Defining Tumor Malignancy: Basis for Development of
Anti-Cancer Vaccines,” Advances in Experimental Medi-
cine and Biology, Vol. 491, 2001, pp. 369-402.
http://dx.doi.org/10.1007/978-1-4615-1267-7_24