Prognostic impact of ABO blood group on type I endometrial cancer in a population of Iranian patients

Abstract

BACKGROUND:

Inherited ABO blood group has been shown to play an important role in the pathogenesis of various gynecological cancers including endometrial carcinoma (EC).

OBJECTIVE:

Our study aimed to determine the prevalence of ABO blood groups in Iranian patients with EC and to investigate the relationship between the blood group and several clinicopathologic parameters in Imam Hossein Hospital.

METHODS:

One hundred and seventy-five EC patients were selected and analyzed for their clinicopathologic details including ABO blood group, age, menopausal status, body mass index (BMI), tumor grade, and stage of the International Federation of Obstetrics and Gynecology (FIGO).

RESULTS:

Endometrioid carcinoma was the most common histological type in this case study. Early stages (I and II) were present in 135 individuals (77.1%) and advanced stages (III and IV) appeared in 40 (22.9%) patients. Blood group A was prominent in patients with EC. There was a significant relationship between blood group A and cancer grade ( $P=$ 0.024). 23.1% of group A had grade III EC, while this grade appeared in 35.2% of the non-A blood group. There was no significant association between ABO blood groups and other EC clinic-pathological results ( $P>$ 0.05).

CONCLUSION:

Although there was no significant relationship between the ABO blood group and the patients’ clinicopathological characteristics, more studies could provide extensive information about any possible relation between the blood group, especially blood group A, EC, and the grade of the tumor.

Keywords

ABO blood groups endometrial carcinoma gynecological cancers

1. Introduction

Endometrial carcinoma (EC) is one of the most common gynecologic malignancies [1] in the female genital tract in developed countries [2, 3]. More than 80% of EC is occurring in postmenopausal women [1, 4] and endometrioid histology is the most common type of endometrial cancers [2]. However, there was a biologically and morphologically variety in endometrial cancer that are different types of tumors, pathogenesis, prognosis, and histopathologic classification [2]. The adjusted incidence rate of EC in Iran is reported from 1.7% to 2.29% during 2004–2008, while the worldwide incidence is 8.2% [5]. The lifetime incidence of endometrial cancer is 1.1% and its mortality rate is 0.4% that reflecting good prognoses’ of disease with early diagnosis [6]. Therefore, early detection of EC is related to an excellent survival rate [2] and a decrease in mortality rate due to this cancer. In recent years, some recent studies have shown that there is a certain correlation between blood group type and endometrial cancer [5]. Some studies assessed the association of ABO blood groups on the prognosis of EC [7]. Therefore, the current study aimed to assess the relationship between ABO blood group and clinically significant parameters such as grade, histopathological stage, and other clinicopathological factors.

2. Materials/patients and methods

This study was performed at Imam Hossein Hospital in Tehran, Iran. The study protocol was approved by the Research Council of Shahid Beheshti University. From 1392 to 1398, all patients with confirmed pathologic diagnosis of EC were identified and retrospectively analyzed for clinicopathological details ( $n=$ 175). Clinical details included ABO blood group, age, menopausal status, body mass index (BMI), tumor grade, stage of the International Federation of Obstetrics and Gynecology (FIGO) Histological classification of EC was based on WHO classification [8]. Tumors, based on their grades, were divided into 3 categories: grade 1 or poor, grade 2 or moderate, grade 3 or severe and were differentiated according to the FIGO grading system [9]. Individuals without ABO blood group, history of gynecological diseases or colorectal cancer, concomitant treatment with tamoxifen, endometrial thickness greater than 15 mm during hormone therapy were excluded from the study. Factors affecting prognosis including grade 1 versus grade 2 and 3 tumors, stages 1 and 2 FIGO versus stages 3 and 4. Myometrial involvement below 50% versus above 50%, lymphatic vasculature invasion versus invasion, lower uterine segment involvement versus non-invasion, pelvic lymph node involvement with/without Paraaort versus non-lymph node involvement and cervical involvement or non-involvement. The FIGO I-II stages are referred to as the early stages, while the FIGO III-IV stages are called advanced stages [10]. ABO blood groups were categorized as A, B, AB, and O. Numerical data were presented as mean $\pm$ standard deviation/SD [range: minimum – maximum]. Classified data are presented as the number of cases (number) and percentage (%). A Chi-square test was used for univariate analysis. All statistical analyzes were performed using IBM SPSS software version 22 for Windows. For all purposes, $p<$ 0.05 was considered statistically significant.

Table 1
Demographic information of patients with endometrial carcinoma

Variables	Number	Percent
Age group
$<$ 40 years old	23	13.4
40–49 years	32	18.3
$\geqslant$ 50 years	120	68.6
BMI
Under weight	3	1.9
Normal	34	21.1
Over weight	77	47.8
Obesity	47	29.2
Menopausal status
Post-menopausal	119	68.8
Pre-menopausal	54	31.2
Blood group
A	64	37.0
B	36	20.8
AB	21	12.1
O	52	30.1
Blood pressure history
Yes	66	38.6
Diabetes history
Yes	36	21.2
Family history of cancer
Yes	31	21.4
Myometrial invasion
$<$ 50%	162	92.6
$\geqslant$ 50%	13	7.4
Nuclear grade
1.00	82	48.2
2.00	37	21.8
3.00	51	30.0
Stage
1.00	118	67.4
2.00	17	9.7
3.00	34	19.4
4.00	6	3.4
Histological type
Endometrioid	117	66.9
Papillary	18	10.3
Clear cell	9	5.1
MMMT carcinosarcoma	10	5.7
Un-differentiated	2	1.1
Malignant mixed tumor	7	4.0
Unknown	12	6.9
Lympho-vascular invasion
Yes	54	32.9
Cervical involvement
Yes	23	14
Lymph nodes involvement
Yes	26	16.8
Lower uterine segment involvement
Yes	17	11.2

Table 2

The association between clinical outcomes of endometrial carcinoma in patients with ABO blood groups

Clinical outcomes	ABO blood groups									A and non-A blood groups
	A (%)		B (%)		AB (%)		O (%)
	$n=$ 66		$n=$ 36		$n=$ 21		$n=$ 52		$P$ value	A, $n=$ 66 (7/37%)		Non-A, $n=$ 109 (62.2%)		$P$ value
Histological type
Endometrioid	45	(68.2)	24	(66.7)	16	(76.2)	32	(61.5)	0.673	45	(68.2)	72	(66.1)	0.772
Other type	21	(31.8)	12	(33.3)	5	(23.8)	20	(38.5)		21	(31.8)	37	(33.9)
Myometrium invasion depth
$<$ 50%	60	(90.9)	32	(88.9)	20	(95.2)	50	(96.2)	0.539	60	(90.9)	102	(93.6)	0.514
$\geqslant$ 50%	6	(9.1)	4	(11.1)	1	(4.8)	2	(3.8)		6	(9.1)	7	(6.4)
Lympho-vascular invasion
Yes	19	(31.1)	8	(23.5)	8	(40)	19	(38.8)	0.447	19	(31.1)	35	(34)	0.709
No	42	(68.9)	26	(76.5)	12	(60)	30	(61.2)		42	(68.9)	68	(66)
Cervical involvement
Yes	10	(15.9)	3	(9.1)	3	(15)	7	(14.6)	0.832	10	(15.9)	13	(12.9)	0.590
No	53	(84.1)	30	(90.9)	17	(85)	41	(85.4)		53	(84.1)	88	(87.1)
Lymph nodes involvement
Yes	10	(16.7)	3	(9.7)	4	(21.1)	9	(20)	0.636	10	(16.7)	16	(16.8)	0.977
No	50	(83.3)	28	(90.3)	15	(78.9)	36	(80)		50	(83.3)	79	(83.2)
Lower uterine segment involvement
Yes	6	(10.2)	5	(15.6)	2	(10.5)	4	(9.5)	0.844	6	(10.2)	11	(11.8)	0.752
No	53	(89.8)	27	(84.4)	17	(89.5)	38	(90.5)		53	(89.8)	82	(88.2)
Nuclear grade
1	40	(61.5)	16	(45.7)	9	(45)	17	(34)	0.060	40	(61.5)	42	(40)	0.024
2	10	(15.4)	6	(17.1)	7	(35)	13	(26)		10	(15.4)	26	(24.8)
3	15	(23.1)	13	(37.1)	4	(20)	20	(40)		15	(23.1)	37	(35.2)
Surgical stage
Early stage (I&II)	52	(78.8)	27	(75)	16	(76.2)	40	(76.9)	0.976	52	(78.8)	83	(76.1)	0.687
Advanced stage (III&IV)	14	(21.2)	9	(25)	5	(23.8)	12	(23.1)		14	(21.2)	26	(23.9)

3. Results

One hundred seventy-six patients met the inclusion criteria and were included in the study analysis. The mean age of patients was 54.47 $\pm$ 11.34 years and ranged from 32 to 85 years. The calculated mean BMI was 8.36 $\pm$ 29.09 and according to the WHO classification, 77 individuals (47.8%) were overweight and 47 (29.2%) were obese. 119 cases (68.8%) were postmenopausal, 66 patients (37%) had a history of hypertension, 36 (20.8%) had a history of known diabetes, and 31 cases (21%) had a history of cancer in first-degree relatives or self-patients.

Endometrioid was the most common type of histology in our patients (66.9%). Early stages (I and II) and advanced stages (III and IV) were present in 135 (77.1%) and 40 (22.9%) patients, respectively. Blood group A was the most common in patients with EC. Correlation of EC clinicopathologic results with ABO blood groups showed a significant relationship between blood group A and cancer grade ( $P=$ 0.024). 23.1% of group A had grade III EC while this grade appeared in 35.2% of non-A blood group. The association between ABO blood groups and other EC clinic-pathological results was not significant ( $P>$ 0.05). Serous papillary in 18 cases (10.3%), MMMT (Carcinosarcoma) in 10 cases (5.7%), and clear cell in 9 other cases (5.1%) were major histological variants. Most of the patients, 162 cases (92.6%) had $<$ 50% myometrial invasion in hysterectomy. Classification by nuclear grade showed that 82 individuals (48.2%) were grade I, 37 people (21.8%) grade II, and 51 cases (30%) grade III. Early stages (I and II) and advanced stages (III and IV) were present in 135 (77.1%) and 40 (22.9%) patients, respectively.

Invasive lymph node invasion was observed in 54 (32.9%), lower uterine septal involvement was seen in 17 (11.2%), pelvic lymph node with/without paraaortic involvement appeared in 26 (16.8%), and cervical involvement was present in 23 individual (14%). The frequency of ABO blood groups is shown in Table 1. The frequency of the blood types A, B, AB, and O was 37%, 20.8%, 12.1%, and 30.1% respectively. Blood type A was the most common in patients with EC. The frequency of non-A and blood group A was 62.2% and 37.7%, respectively. There was no association between ABO blood groups and the studied clinicopathologic factors. But when ABO blood groups were treated as two different types of non-A and A, the association of EC clinicopathologic results with ABO blood groups showed a significant relationship between blood type A and the grade of cancer ( $P=$ 0.024).

Grade III EC was 23.1% in blood group A and 35.2% in the non-A blood group. However, the association between ABO blood groups and other EC clinic-pathological results was not significant ( $P>$ 0.05). Table 2, illustrates patient characteristics and the relationship between ABO blood groups and clinicopathologic factors for EC.

4. Discussion

The ABO locus is located on chromosome 9 (9q34). Numerous studies have shown that different ABO blood groups may affect different cancerous and non-cancerous processes in the body [11]. The precise mechanisms and role of the ABO blood group in the pathogenesis of cancer are not well understood. However, several assumptions have been proposed. Antigens of specific blood group of neoplastic cells may lead to biological aggressive behaviors [11]. In particular, it has been shown that the presence of antigen A may enhance cellular motility and facilitate cellular interactions between neoplastic cells [7]. Also, ABO blood group antigens may contribute to immune resistance and apoptosis (programmed cell death) [12]. In addition, a previous study showed an association between ABO blood groups and altered levels of molecules involved in inflammation, immune defense, and cell adhesion [13]. Concerning malignancies in women, there are few studies examining the relationship between ABO blood group and EC [8, 14]. In our study, in general, type A was the largest ABO blood group in patients with EC. Our findings are similar to those in Siberia [8], China [15], and Italy [16, 17], all of which showed that type A is the most common ABO blood group present in patients with EC. However, our findings are in contrast to other studies in Georgia and Saudi Arabia in which the O blood group was predominant in patients with endometrial cancer [18, 19]. In addition, the findings of our study were opposed to an Armenian study, which showed that the AB type is the most common ABO blood group in patients with EC [20].

Mohammad Reza Keramati and colleagues [21] studied the prevalence of ABO in Iran in different cities in northern Iran and observed the high prevalence of O blood group. Qassemi et al. [22] also reported a high prevalence of O blood type in the general population in Yazd. These studies included small sample sizes of 150 to 2000 individuals in each study, which were not large enough to indicate that type O is the most common ABO blood group in the female population.

In our study, blood group A may be more sensitive to EC. However, no definitive conclusions can be drawn at this stage and a large-scale case study at the country level is needed.

In our study, patients with blood group A had a lower risk of developing high-grade endometrial cancer (G3), which was similar to the study in Italy [17].

Tumor grading is important because it is crucial in lymphadenectomy and subsequent systemic or radiotherapy treatment [23]. Also, surgical procedures to maintain fertility are only possible in grade 1 tumors and stage one endometrial cancer of the endometrium, and it is, therefore, important to determine the tumor grade [23]. Therefore, it is genetically important to know that grade 2 and 3 endometrial cancers risk is eliminated based on the blood group [17].

Our findings showed that there was no significant relationship between ABO blood group and staging, FIGO myometrial depth, invasive lymph node invasion, uterine segmental involvement, pelvic lymph node involvement with/without paraaortic captivity, and cervical involvement. This is attributed to the small sample size in our study. However, a lack of association between the staging and blood group was also reported in other studies [17, 24]. Our work is the first study that investigates the role of ABO blood group in an Iranian EC population. This study, like some previous related investigations, had some limitations [8, 24] such as the research design of a retrospective cross-sectional study and/or the absence of a more robust design, a case-control study. In addition, this study is performed on a single center of Iran, and therefore its results may be ethnically limited and not generalized nationwide.

5. Conclusion

A large-scale case-control study is needed to prove that the ABO blood group could or could not be a useful, easy and inexpensive marker for Iranian patient selection and personalized management of EC patients.

Footnotes

Acknowledgments

We would like to appreciate all who helped us in doing this research.

This study was supported by IR.SBMU.RETECH. REC. Grant number 1398.693.

Conflict of interest

The authors declare that they have no conflict of interest.

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Prognostic impact of ABO blood group on type I endometrial cancer in a population of Iranian patients

Abstract

BACKGROUND:

OBJECTIVE:

METHODS:

RESULTS:

CONCLUSION:

Keywords

1. Introduction

2. Materials/patients and methods

Table 1 Demographic information of patients with endometrial carcinoma

4. Discussion

5. Conclusion

Footnotes

Acknowledgments

Conflict of interest

References

Table 1
Demographic information of patients with endometrial carcinoma