IJC

International Journal of Cancer

ABO blood group and nasopharyngeal carcinoma risk in a

population of Southeast China
Liming Sheng1*, Xiaojiang Sun1*, Lizhen Zhang1 and Dan Su2
1
2

Department of Radiation Therapy, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China

Cancer Research Institute, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China

Nasopharyngeal carcinoma (NPC) is a common head and

neck malignant neoplasm in China, especially in the southern
provinces.1 The EpsteinBarr virus (EBV) is the major risk
factor for NPC,2 especially undifferentiated carcinomas
(World Health Organization Type III). Cigarette smoking,3,4
alcohol consumption,5 salt-preserved food6,7 and family history of cancer8 may also contribute to the development of
this disease. However, EBV infection is approximately ubiquitous and not all EBV infection groups develop NPC.9 Therefore, host genetic susceptibility is a very important risk factor
in NPC pathogenesis, contributing to the variation in individual cancer risk.
The ABO blood group has been studied over a century.
The ABO gene, located on chromosome 9q34.1 to 9q34.2,
encodes a specic glycosyl transferase that synthesizes A and
B antigens to form the ABO blood group antigen.10 ABO
blood group antigens, the most immunogenic of all the blood
group antigens, are of clinical signicance in transfusion
medicine. Aside from red blood cells, wide variety of human
tissues and most epithelial and endothelial cells also express
Key words: nasopharyngeal carcinoma, ABO blood group,
molecular epidemiology
L.S. and X.S. contributed equally to this work and should be
regarded as rst joint authors
DOI: 10.1002/ijc.28087
History: Received 13 June 2012; Accepted 21 Jan 2013; Online 6 Feb
2013
Correspondence to: Dan Su, MD, PhD, Cancer Research Institute,
Zhejiang Cancer Hospital, 38 Guangji Road, Hangzhou, Zhejiang,
China 310022, Tel.: 186-571-88122422, Fax: 186-571-88122587,
E-mail: Vip20112012@163.com

C 2013 UICC
Int. J. Cancer: 133, 893897 (2013) V

the ABO blood group antigens.11,12 Although the elaborate

physiologic function of the ABO blood group antigens
remains unknown, no disease results from the lack of expression of ABO blood group antigens. Many studies have
reported that the ABO blood group is correlated with susceptibility to a number of malignancies.1316 A denite correlation has been established between the ABO blood group and
pancreatic cancer. The non-O blood type increases the risk of
pancreatic cancer, with the high risk observed among populations with blood group B.17 Such correlation between ABO
blood group and NPC remains controversial. The initial
research by Seow et al.18 in 1964 demonstrated the absence of
an association between ABO blood group and NPC. However,
in 2011, Turkoz et al.19 indicated that the ABO blood group
is related to NPC susceptibility. Blood group A increases risk,
whereas blood group O shows a protective effect.
The reports of these two previous studies are limited by
their small sample size. To further understand the relationship between ABO blood group and the risk of NPC, we conducted a large-scale case-control study in a Chinese
population. We assessed whether ABO blood group was a
risk factor for NPC. In addition, we evaluated the relationship between the ABO blood group and the pathologic variables of NPC patients.

Material and Methods

Study population

A total of 1,538 patients with NPC who were newly diagnosed and treated in Zhejiang cancer hospital, Hangzhou,
China, between January 2004 and December 2011, were enrolled in this study. All patients had denitive

Cancer Genetics

Previous studies found that the ABO blood type alters the individual susceptibility of some malignancies. However, whether
such an association exists between ABO blood type and nasopharyngeal carcinoma (NPC) remains unknown. A case-control
study was conducted, with 1,538 patients who had NPC and 1,260 cancer-free controls. The association between ABO blood
type and NPC incidence was evaluated using unconditional logistic regression analysis. Compared with subjects with blood
type O, a relatively higher risk was observed among cases with blood types A or AB, with ORs (95% confidence interval) of
1.287 (1.072 2 1.545), p 5 0.007 and 1.390 (1.007 2 1.919), p 5 0.045, respectively, after adjusting for gender, age, smoking
status and family history of cancer. The rate of distant metastasis was significantly higher among male patients with blood
type A than in patients with non-A blood types (6.8 vs. 3.5%, p 5 0.027). Our results suggest that blood types A or AB is
associated with an increased risk of NPC. Further studies are needed to confirm this association and to explore the mechanisms involved.

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ABO blood group and NPC risk in Southeast China

Cancer Genetics

Whats new?
The ABO blood group has been reported to alter individual susceptibility to a number of malignancies, but whether such an
association exists between the ABO blood group and nasopharyngeal carcinoma (NPC) remains unknown. In a large-scale
case-control study carried out in China, the authors observed a statistically significant increased risk for NPC among patients
with blood group A or AB, compared with those with blood group O. Blood type A was also associated with more advanced
NPC in male patients. The results suggest that ABO blood group antigens may play an important role in the carcinogenesis of
nasopharyngeal cancer.

histopathologic conrmation. Patients who received preoperative chemotherapy or radiotherapy were excluded. The
clinical stage for all patients was determined according to
the 2010 Union for International Cancer Control cancer
staging system. Patients with any other malignant diseases
were excluded. In addition, a population control of 1,260
outpatients was randomly selected from a pool of cancerfree subjects in the same hospital during the same period.
Of these subjects, 45% was admitted to the hospital for
checkup, 35% for blood donation and 20% for a variety of
other acute illness, including appendicitis, infection of the
upper respiratory tract or esoenteritis. Detailed information,
such as family history of cancer and history of smoking
were obtained by trained interviewers using a structured
questionnaire. Informed consent was provided by all cases
and controls. The study was approved by the ethics committee of Zhejiang Cancer Hospital.
Smoking status was divided into three groups based on
smoking habits. We classied tobacco consumption as never
smoked (never smoked during their lifetime), light smoker
(<30 cigarettes per day) and heavy smoker (>30 cigarettes
per day). When at least one rst-degree family member was
diagnosed with cancer, the family history was considered
positive for cancer. ABO blood group was detected using
routine clinical tests.
Statistical analysis

A Pearsons chi-square test was used to assess the frequencies

in demographic variables, gender, smoking status and family
history of cancer between the cases and the cancer-free controls and to evaluate the correlation between ABO blood
group in cases and clinical stage. A Students t-test was used
to compare patient age. The associations between ABO blood
group and the risk for NPC, as well as ABO blood type and
distant metastasis in NPC patients, were evaluated using
unconditional logistic regression analysis. All statistical calculations were performed with SPSS 13.0 for Windows
(Chicago, IL). A p value of <0.05 was considered statistically
signicant.

Results
Characteristics of NPC patients and cancer-free controls

This study includes 1,538 cases of NPC and 1,260 cancer-free

controls. Table 1 shows the distribution of age, gender, smoking status and family history of cancer in NPC patients and

cancer-free controls. The mean age was 49.5 (range, 1186

yr) for NPC patients and 48.8 (range, 1280 yr) for control
subjects. Of the 1,538 NPC patients, 35.4% were female and
64.6% were male; 19.2% never smokes, 41.5% were light
smokers and 39.2% were heavy smokers. Most patients had
no family history of cancer, but 6.4% of patients had. The
variables had similar proportions in 1,260 cancer-free controls; hence, no statistically signicant differences were found
compared with those in the cases.
ABO blood group and NPC risk

Distributions of ABO blood groups are shown in Table 2.

The proportions of blood types A and AB were higher in
NPC cases than those in controls (30.6 vs. 27.1%, 6.9 vs.
5.7%) and the proportion among NPC with blood type O
than that in the controls (37.4 vs. 42.8%). This frequency distribution of ABO blood groups in the controls was similar to
a previous study on a Han population in Eastern China.20
Compared with blood type O individuals, the adjusted
odds ratios of NPC risk among those with blood group A or
AB were 1.287 (95% CI, 1.072 2 1.545, p 5 0.007) and 1.390
(95% CI, 1.007 2 1.919, p 5 0.045), after adjusting for gender,
age, smoking status and family history of cancer. However,
only a borderline signicant association of blood type B and
Table 1. Characteristics of NPC patients and cancer-free controls
Variable

Cases
(n 5 1,538)

Controls
(n 5 1,260)

Age, yr (mean 6 SD)

49.5 6 11.2

48.8 6 11.4

0.090

Age

No.

No.

<65

1,405

91.4

1,140

90.5

65

133

8.6

120

9.5

Gender

0.421

0.307

Female

545

35.4

470

37.3

Male

993

64.6

790

62.7

296

19.2

247

19.6

Smoking status

0.765

Never
Light

639

41.5

536

42.5

Heavy

603

39.2

477

37.9

No

1,439

93.6

1,191

94.5

Yes

99

6.4

69

5.5

Family history of cancer

0.299

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Int. J. Cancer: 133, 893897 (2013) V

895

Sheng et al.

Table 2. ABO blood group and risk for NPC

Cases
Variable

No. %

Table 3. Clinicopathological characteristics in patients with distant

metastasis and without distant metastasis

Controls
No. %

Adjusted
95%CI
OR1

p2

ABO group
O

575 37.4 539 42.8 1

471 30.6 342 27.1 1.287

1.0721.545 0.007

386 25.1 307 24.4 1.179

0.9751.427 0.090

AB

106 6.9

72

5.7

1.390

1.0071.919 0.045

A 1 AB

577 37.5 414 32.9 1.307

1.1001.553 0.002

A 1 B 1 AB 963 62.6 721 57.2 1.252

Variable

M0
(n 5 1480)1

M1
(n 5 58)1

Age

No.

No.

<65

1,353

91.4

52

89.7

65

127

8.6

10.3

Female

532

35.9

13

22.4

Male

948

64.1

45

77.6

Gender

0.639

0.035

Smoking status

1.0751.458 0.004

p2

0.215

Never

290

19.6

10.3

Light

612

41.4

27

46.6

Heavy

578

39.1

25

43.1

Family history of cancer

NPC risk was shown, although subjects with blood type B

had an increased risk for NPC (adjusted OR of 1.179, 95%
CI 5 0.975 2 1.427, p 5 0.090).
1

ABO blood group and distant metastasis in NPC

We analyzed the distribution of age, gender, smoking status

and family history of cancer in NPC patients without distant
metastasis and with distant metastasis before we assessed the
association between ABO blood grouping and distant metastasis in NPC by casebase reference analysis (patient without
distant metastasis was used as the control). Age, smoking status and family history of cancer in the two groups had no
statistically signicant differences, but the proportion of male
patients was signicantly higher in the NPC patients with
distant metastasis than in those without distant metastasis
(77.6 vs. 64.1%, p 5 0.035; Table 3). Pearsons chi-square test
and unconditional logistic regression analyses were stratied
by gender. The results showed that male patients with blood
group A had higher distant metastatic rates than those with
non-A blood types (6.8 vs. 3.5%, p 5 0.027), and male
patients with blood group A had a 1.949-fold higher risk of
distant metastasis than those with non-A blood types (95%
CI: 1.042 2 3.646; p: 0.037) after adjusting for age, smoking
status and family history of cancer. No statistically signicant
differences were found in the female patients (Table 4).

Discussion
Recently, much attention has been given to the connection
between ABO blood group and tumor risk. However, the
relationship between ABO blood group and NPC has not
been well addressed. In this study, we observed a statistically
signicant increased risk for NPC among patients with blood
type A or AB, compared with those with blood group O.
Blood type A was also associated with more advanced NPC
in male patients. To our knowledge, this is the rst largescale case-control study that shows a correlation between
ABO blood group and NPC risk a Chinese population.
Our ndings were consistent to a previous study in
NPC,19 and in close agreement with the results from other
C 2013 UICC
Int. J. Cancer: 133, 893897 (2013) V

0.194

No

1,381

93.3

55

84.8

Yes

99

6.7

5.1

M0, no distant metastasis; M1, distant metastasis.

Bold values are statistically significant (p < 0.05).

cancers, such as pancreatic cancer,2123 hepatocellular carcinoma24 and gastric cancer,2527 which suggest that the
increased risk of cancer is associated with non-O blood
groups. However, three recent genome-wide association studies (GWAS) on NPC did not show the association of ABO
with cancer risk.2830 Many reasons could possibly explain
this discrepancy. First, our study reects the association of
ABO phenotype with NPC risk. Those GWAS may also nd
that the SNPs within the ABO locus are candidate NPC-associated genetic variations, but their correlations are not stronger than those of other SNPs. Only the top SNPs with the
smallest p-values were further validated in those GWAS. Second, although our study is a relatively large case-control
study, the ndings are still preliminary. Independent large
studies are warranted to conrm these results.
Previous studies suggested that ABO antigens mediate microbial infections, including Helicobacter pylori31,32 and Norwalk virus.33 Therefore, we hypothesize that ABO status may
also interact with EBV, thereby inuencing nasopharyngeal
carcinogenesis. However, the lack of information on EBV
infections limits this study, which may represent a bias in the
analysis. EBV is almost ubiquitous in the Southeast Chinese
population, but we do not know if the cases and controls in
our cohort had a different infection ratio. The relationship
between ABO blood group and EBV positivity needs to be
further elucidated.
In this study, we also observed that the rate of distant metastasis was signicantly higher in male patients with blood
type A than those with other blood types. Previous studies34,35 also found that blood type O appears to prevent the
growth and spread of tumors. The ABO blood group is
determined by the expression of A and B antigens on the

Cancer Genetics

Adjusted odds ratios: adjusted for gender, age, smoking status and
family history of cancer.
2
Bold values are statistically significant (p < 0.05).

896

ABO blood group and NPC risk in Southeast China

Table 4. ABO blood group and distant metastasis in male and female patients with NPC
M0
Variable

No.

ABO group (Male patients)

948

M1
%

No.

AOR2

95% CI

p3

1.0423.646

0.0374

0.514-5.318

0.400

45

Non-A

658

96.5

24

3.5

290

93.2

21

6.8

ABO group (Female patients)

P1

532

1
0.0234

1.949

13

Non-A

377

97.9

2.1

155

96.9

3.1

1
0.466

1.653

Pearsons chi-square test.

Adjusted for age, smoking status and family history of cancer.
3
Unconditional logistic regression analysis.
4
Bold values are statistically significant (p < 0.05).

Cancer Genetics

surface of red blood cells and anti-A and anti-B antibodies in

the serum. These two antigens are oligosaccharide antigens
expressed on the membranes of red blood cells and on normal epithelial and endothelial cells. In most human carcinomas, ABO blood group antigen expression on cancer cells is
modied by hypermethylation of ABO gene promoter, which
is one of the characteristics of malignant neoplasms.36 The
changes in ABO blood antigens on cancer cells may correlate
with tumor invasiveness or metastatic potential, thereby
increasing cell motility through alterations in the glycosylation of integrins.37 Furthermore, the core disaccharide structure of the ABO blood group (H) substance, the Thomsen
Friedenreich antigen, may inuence tumorendothelial cell
interactions, which are related to cancer metastasis.38 Recent
studies have also revealed that SNPs at the ABO blood group
gene locus are important determinants of soluble intercellular
adhesion molecule 1 (sICAM-1)39 and tumor necrosis factor-

alpha (TNF-a).40 The soluble ICAM-1 released by cancer

cells binds human rhinoviruses. Increased sICAM-1 concentration is related to NPC distant metastasis.41 TNF-a, one of
the important cytokines secreted by the macrophage or cancer cells, is closely related to NPC progression and
prognosis.42
In conclusion, our ndings suggest that ABO blood type
is related to NPC risk in Chinese populations. Individuals
with blood type A or AB have increased NPC risk. Additionally, the male patients with blood group A have higher rates
of distant metastasis than those in other blood groups. However, this study has certain limitations. Further studies of the
interaction between ABO blood antigens and EBV infection
are needed. Furthermore, progression-free survival and overall survival data need to be collected to evaluate whether
blood group A is an independent predictor for NPC
prognosis.

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