Association of blood group types and clinico-pathological features of gynecological cancers (GCs).

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Abstract

BackgroundGynecological cancers (GCs) affect the reproductive system of females, and are of multiple types depending on the affected organ most common of which are cervical, endometrial, ovarian cancers. Among different risk factors for GCs, ABO blood group system is considered as one of the pivotal contributing factors for increased susceptibility of GCs. The aim of our study was to report on the demographics of GC patients and to investigate the relationship between the ABO blood group system and the risk of acquiring GC in our population.MethodsThe current retrospective cross-sectional study was carried out between the years of 2016 and 2023. The sample included all the patients having age > 18 with a record of blood group and confirmed histological or cytological diagnosis as per International Federation of Gynecology and Obstetrics (FIGO) guidelines. A comprehensive review of the charts was conducted to gather data including demographics, tumor characteristics, comorbidities, adverse effects, and treatment methods.ResultsA total of 543 female patients were included in the study. The mean age of patients was 61.6. The three most common BG in our GC cases were as O + (43.8%), followed by A + (26%), and B + (15.5%). Among comorbidities, hypertension (HTN), diabetes mellitus (DM), dyslipidemia were the top three affecting GC patients. A significant association (p < 0.05) between ABO BG and serous histology in endometrial cancer was found. ABO blood group and fallopian cancer showed a significant relationship between serous histology and B blood group (p < 0.05). For ovarian cancer a significant association between AB blood group and recurrence rates were found (p < 0.05). In case of the patient dependent GCs, a significant association between ovarian cancers and recurrence, fallopian tube cancers and adverse events and survival status, vaginal/vulval cancers and TNM stage and mixed GCs and tumor type (carcinoma) was observed (P < 0.05). Furthermore, multinomial analysis between various confounding factors and GCs revealed that the risk of Cervical, Endometrial and Ovarian cancers to be significant for Type B BG (P < 0.05).ConclusionOur study found that O + BG was the most prevalent among our population. Furthermore, there was a significant association between BG B and endometrial and serous histology in fallopian tube and between BG AB and ovarian malignancies, respectively. Additionally, multinomial analysis revealed higher risk of Cervical, Endometrial and Ovarian cancers for Type B BG (P < 0.05).
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Methods

This retrospective cross-sectional study was conducted at Princess Noorah Oncology Center (PNOC) at King Abdulaziz Medical City (KAMC), a tertiary hospital in Jeddah, Saudi Arabia. The study was carried out in line with the Helsinki protocol and an ethical approval was approved by the Institutional Review Board of King Abdullah International Medical Research Centre (KAIMRC), a research wing of KSAU-HS, Jeddah ( Reference No: IRB/0505/23; SP23J/014/02; Dated: 27/02/2023 ). Institutional Review Board (IRB) covered the data collection from the electronic database (BESTCare system) of the hospital. Using a consecutive sampling technique, the study sample included all GC patients who fit the criteria and had been admitted to PNOC in NGHA, KAMC, between the periods of January 2016 to May 2023. Patients medical records were extracted from the BESTCare system based on the International Classification of Diseases-10 (ICD-10) codes of GCs i.e., endometrial, cervical, ovarian, vaginal, and vulvar cancer C53 (0–1–8- 9), C54 (0–1–2–3–8–9), C56, C52, C51 (0–1–2–8–9), C48(2–1) C57 (0–1–2–3–4–7–8), C58, C55. The eligibility criteria included GCs patients above 18 years old and having documented records of their blood groups. All the patients who had double primary GCs or had a gynecological primary cancer that metastasized to any organ either gynecological organ or non-gynecological were taken into consideration. Conversely, patients with a primary GC with any other primary non-gynecological disease were excluded. The included data was categorized into four sections: the first section included the patients' demographics data such as age, weight (kg), body mass index (BMI) (kg/m 2 ), height (cm), marital status, blood groups, work status, educational level, income, and dwelling. The second section included patients' health information such as BG type, family history of GC, comorbidities, allergic reaction, blood disorder. Patients with anemia, idiopathic thrombocytopenia purpura (ITP), disseminated intravascular coagulation (DIC), hemophilia, and abnormal platelet count were considered to have blood disorders. The third section included the treatment options provided. The fourth section included the clinico-pathological characteristics of gynecological cancer, which included tumor type, histopathology of the tumor, tumor stage tumor anatomical position, recurrence, adverse events and survival. Tumor type, FIGO stage, tumor grade, tumor stage, tumor histopathology, tumor anatomical position, organ, and recurrence were obtained from pathological lab results. Tumor characteristics were determined by using the TNM Staging System (tumor size, involvement of lymph nodes, and metastasis). The SPSS version 20 statistical software (Statistical Package for Social Sciences, SPSS version 20, Chicago, IL, USA) was used for the statistical analysis of the data. For demographic data of the patients, quantitative data was presented by the mean and standard deviation, while qualitative data was presented by frequency and percentage. Chi-square test and fisher exact test were used to compare different qualitative variables together. The ABO blood group was also compared with different clinical parameters. A multinomial regression analysis was performed to investigate the relationship between risk variables and blood classes (O, A, B, and AB), which were mutually exclusive categories. The other blood group categories were compared with the reference category, which was assigned to "O." Age, BMI, obesity, and the various locations of tumors in female reproductive organs were simultaneously entered into the model as independent factors. P value of ≤ 0.05 was set as the statistical significance for interpretation of the association between variables.

Results

Our studied population of GC patients comprised of 543 females. The demographics of the overall population enrolled have been summarized in Table  1 . The mean (± SD) age of the participants was 61.6 (± 14.52) years. In terms of weight, the mean was calculated to be 76.1- ± 20.88 kg. The participant heights had a mean value of 153.5 (± 9.07) cm. Moreover, the mean body mass index BMI (the weight in kilograms divided by the square of the height in meters) was 31.8 ± 9.07 kg/m 2 . Table 1 Demographic profile of study participants n  = 543 % Parameters Mean (SD) Age 61.6 (14.52) Weight (kg) 76.1 (20.88) Height (cm) 153.5 (9.97) BMI (kg/m 2 ) 31.8 (9.07) Marital Status Single 36 6.6 Married 419 77.2 Divorced / Widow 81 14.9 Not found 7 1.3 Working status Employed 27 5.0 Unemployed 506 93.2 Not found 10 1.8 Income (n = 537) Poor 0 0 Rich 18 3.4 Not found 519 96.6 Children No children 47 8.7 1–2 children 57 10.5  > 2 children 228 42.0 Not found 211 38.9 Dwelling Urban 95 17.5 Rural 13 2.4 Not found 435 80.1 Blood Group A- 7 1.3 A +  141 26.0 B- 7 1.3 B +  84 15.5 O- 31 5.7 O +  238 43.8 AB +  24 4.4 Not found 11 2.0 Education level ( n  = 403) Illiterate 7 1.7 Can Read & Write 17 4.2 High school 15 3.7 Elementary/ Intermediate 8 2.0 Undergraduate 11 2.7 Graduate 9 2.2 Not found 336 83.4 Recorded Gynecological cancer* ( n  = 715) Cervix 83 11.6 Endometrium 327 45.7 Ovaries 183 25.6 Peritoneum 52 7.3 Fallopian tube 53 7.4 Vagina/ Vulva 17 2.4 * includes multiple sites as recorded in the database Demographic profile of study participants * includes multiple sites as recorded in the database Furthermore, 419 (77.2%) of patients were married and 506 (93.2%) were unemployed. In our sample, the distribution of blood groups was as follows: O + constituted 238 participants (43.8%), A + and comprised 141 participants (26%), and B + accounted for 84 participants (15.5%) (Table  1 ). Among comorbidities, we found that hypertension (HTN), diabetes mellitus (DM), and dyslipidemia were the top three ones. Majority of the patients (95.4%) denied the positive family history of gynecological cancers. All reported comorbidities are listed in Table  2 . In addition, we found that most of the patients (75.3%) underwent surgical intervention of the tumor tissues. (65%) and (39.6%) underwent chemotherapy and palliative care respectively. Only a small percentage (3.5%) treated with immunotherapy. All treatment options used are enlisted in Table  3 . Table 2 Details of recorded comorbidities of gynecological malignancies patients Out of total ( n  = 543 # ) % Family history of Gynecological cancers 25 4.6 Diabetes mellitus 243 44.8 Asthma 47 8.7 Hypertension 262 48.3 Heart disease 57 10.5 Strokes 28 5.2 Dyslipidemia 104 19.2 Hypothyroidism 70 12.9 Allergies/ irritation 53 9.8 Blood disorders 70 12.9 # the numbers and the percentage represent the patients who had a record of the comorbidities Table 3 Provided treatment modalities to the gynecological malignancy patients n  = 543 % Treated with chemotherapy  353 65.0 Underwent surgery for treatment 409 75.3 Treated with radiation 211 38.9 Treated with immunotherapy 19 3.5 Palliative care 215 39.6 Details of recorded comorbidities of gynecological malignancies patients # the numbers and the percentage represent the patients who had a record of the comorbidities Provided treatment modalities to the gynecological malignancy patients The electronic database recorded 715 incidences of gynecological cancer in our 543 patients. The cancers were recorded as seven different location types as Cervix, Endometrium, Ovaries, Fallopian tube, Peritoneum, Vagina and Vulva. Among them, the three most common cancers affecting our patients were Cervical, Endometrial and Ovarian cancers. EC was the most recorded GC with 283 of 543 (60.2%) being affected, followed by Ovarian (114/543; 21%) and Cervical cancers (63/543; 11.6%) while vaginal/vulvular cancer was the least (14/543; 2.6%). The details of the associations are provided in the Tables 4 and 5 . Table 4 represented the cancers as reported for each patient as per the gynecological organs involved and were 715 incidences (hence multiple entries as per organ involved in one patient), while Table  5 represents the primary involved organs involved in patients (n = 543). Furthermore, we did not find any direct significant association between the distribution of ABO BGs and various GC’s. Table 4 The association of ABO blood group and various gynecological cancers in our studied population Blood group Recorded Gynecological cancer* ( n  = 715) O A B AB p Total n  = 269 % n  = 148 % n  = 91 % n  = 24 % Cervix  Yes 83 41 (49.4) 23 (27.7) 13 (15.7) 6 (7.2) 0.432*  No 460 228 (49.6) 125 (27.2) 78 (17.0) 18 (3.9) Endometrium  Yes 327 167 (51.1) 88 (26.9) 53 (16.2) 10 (3.1) 0.187*  No 216 102 (47.2) 60 (27.8) 38 (17.6) 14 (6.5) Ovaries  Yes 183 85 (46.4) 50 (27.3) 34 (18.6) 11 (6.0) 0.581*  No 360 184 (51.1) 98 (27.2) 57 (15.8) 13 (3.6) Peritoneum  Yes 52 23 (44.2) 14 (26.9) 11 (21.2) 3 (5.8) 0.873*  No 491 246 (50.1) 134 (27.3) 80 (16.3) 21 (4.3) Fallopian tube  Yes 53 22 (41.5) 16 (30.2) 10 (18.9) 4 (7.5) 0.661*  No 490 247 (50.4) 132 (26.9) 81 (16.5) 20 (4.1) Vagina/Vulva  Yes 17 8 (47.1) 4 (23.5) 3 (17.6) 2 (11.8) 0.441†  No 515 261 (20.7) 144 (28.0) 88 (17.1) 22 (4.3) * chi-squared test †fisher’s exact test Table 5 The association of ABO blood group and various gynecological cancers (Patient Corrected) in our studied population Blood group  Patient Corrected Gynecological cancer* ( n =532) O A B AB p † Total n =269 % n =148 % n =91 % n =24 % Cervix 63 32 (50.8) 17 (27.0) 10 (15.9) 4 (6.3) 0.275 Endometrium 283 149 (51.0) 81 (27.7) 43 (14.7) 10 (3.4) Ovaries 114 60 (52.2) 29 (25.2) 20 (17.4) 5 (4.3) Fallopian 31 10 (31.3) 11 (34.4) 8 (25.0) 2 (6.3) Vagina/Vulva 14 9 (64.3) 2 (14.3) 1 (7.1) 2 (14.3) Mix 27 9 (33.3) 8 (29.6) 9 (33.3) 1 (3.7) †fisher’s exact test *11 patients didn’t have a record of ABO Blood Group The association of ABO blood group and various gynecological cancers in our studied population * chi-squared test †fisher’s exact test The association of ABO blood group and various gynecological cancers (Patient Corrected) in our studied population †fisher’s exact test *11 patients didn’t have a record of ABO Blood Group A significant association was noticed between the type B blood group and serous histology type, mixed/unknown/other histology in EC patients with a p -value equal to 0.024 for the recorded patient independent GCs (Supplementary Tables). Additionally, we also found a significant association between type B blood group and serous histology type in patient independent fallopian tube GCs ( p -value = 0.015). Furthermore, our study revealed a significant correlation between AB blood group and recurrence rates in ovarian cancer ( p -value = 0.026). We did not find any significant associations between ABO blood groups and the other enlisted clinico-pathological characteristics in any other patient independent GCs (Tables 6 , 7 , 8 , 9 , 10 and 11 ). Table 6 The association of clinico-pathological characteristics of cervical cancer patients with ABO blood groups Blood group Cervical Cancer Patients O A B AB p Total n  = 32 % n  = 17 % n  = 10 % n  = 4 % Tumor type  Tumor type Adenocarcinoma   Yes 8 5 (15.6) 2 (11.8) 0 (0.0) 1 (25.0) 0.412   No 55 27 (84.4) 15 (88.2) 10 (100.0) 3 (75.0)  Tumor type Squamous cell carcinoma(SCC)   Yes 35 16 (50.0) 9 (52.9) 7 (70.0) 3 (75.0) 0.626   No 28 16 (50.0) 8 (47.1) 3 (30.0) 1 (25.0)  Tumor type Carcino-sarcoma (MMMT)   Yes 1 0 (0.0) 0 (0.0) 1 (10.0) 0 (0.0) 0.222   No 62 32 (100.0) 17 (100.0) 9 (90.0) 4 (100.0)  Tumor type Adeno-squamous-carcinoma   Yes 2 2 (6.3) 0 (0.0) 0 (0.0) 0 (0.0) 0.721   No 61 30 (93.8) 17 (100.0) 10 (100.0) 4 (100.0)  Tumor type sarcoma   Yes 1 1 (3.1) 0 (0.0) 0 (0.0) 0 (0.0)  > 0.99   No 62 31 (96.9) 17 (100.0) 10 (100.0) 4 (100.0)  Tumor type carcinoma   Yes 9 4 (12.5) 4 (23.5) 1 (10.0) 0 (0.0) 0.667   No 54 28 (87.5) 13 (76.5) 9 (90.0) 4 (100.0) Histology Tumor  Histology serous   Yes 2 2 (6.3) 0 (0.0) 0 (0.0) 0 (0.0) 0.721   No 61 30 (93.8) 17 (100.0) 10 (100.0) 4 (100.0)  Histology Endometrioid   Yes 5 4 (12.5) 1 (5.9) 0 (0.0) 0 (0.0) 0.688   No 58 28 (87.5) 16 (94.1) 10 (100.0) 4 (100.0)  Histology clear cell   Yes 2 1 (3.1) 1 (5.9) 0 (0.0) 0 (0.0)  > 0.99   No 61 31 (96.9) 16 (94.1) 10 (100.0) 4 (100.0)  Histology Neuro-endocrine   Yes 3 3 (9.4) 0 (0.0) 0 (0.0) 0 (0.0) 0.651   No 60 29 (90.6) 17 (100.0) 10 (100.0) 4 (100.0)  Histology Epithelial   Yes 12 4 (12.5) 5 (29.4) 3 (30.0) 0 (0.0) 0.312   No 51 28 (87.5) 12 (70.6) 7 (70.0) 4 (100.0)  Histology Mixed/unknown/other   Yes 29 13 (40.6) 8 (47.1) 6 (60.0) 2 (50.0) 0.767   No 34 19 (59.4) 9 (52.9) 4 (40.0) 2 (50.0)  TNM stage T   T1 6 5 (15.6) 1 (5.9) 0 (0.0) 0 (0.0) 0.736   T2 3 2 (6.3) 0 (0.0) 0 (0.0) 1 (25.0)   T3 8 5 (15.6) 2 (11.8) 1 (10.0) 0 (0.0)   T4 6 2 (6.3) 2 (11.8) 2 (20.0) 0 (0.0)   Not found 40 18 (56.3) 12 (70.6) 7 (70.0) 3 (75.0)  TNM stage N   N0 4 3 (9.4) 1 (5.9) 0 (0.0) 0 (0.0) 0.876   N1 9 5 (15.6) 2 (11.8) 2 (20.0) 0 (0.0)   Nx 9 6 (18.8) 2 (11.8) 0 (0.0) 1 (25.0)   Not found 41 18 (56.3) 12 (70.6) 8 (80.0) 3 (75.0)  TNM Stage   M0 3 3 (9.4) 0 (0.0) 0 (0.0) 0 (0.0) 0.537   M1 7 3 (9.4) 2 (11.8) 2 (20.0) 0 (0.0)   Mx 11 8 (25.0) 2 (11.8) 0 (0.0) 1 (25.0)   Not found 42 18 (56.3) 13 (76.5) 8 (80.0) 3 (75.0)  Tumor grade   G1 4 4 (12.5) 0 (0.0) 0 (0.0) 0 (0.0) 0.252   G2 14 4 (12.5) 5 (29.4) 3 (30.0) 2 (50.0)   G3 34 16 (50.0) 11 (64.7) 6 (60.0) 1 (25.0)   Not found 11 8 (25.0) 1 (5.9) 1 (10.0) 1 (25.0)  FIGO Stage   Stage I 9 4 (12.5) 3 (17.6) 1 (10.0) 1 (25.0) 0.550   Stage II 10 5 (15.6) 2 (11.8) 1 (10.0) 2 (50.0)   Stage III 15 10 (31.3) 4 (23.5) 1 (10.0) 0 (0.0)   Stage IV 20 8 (25.0) 6 (35.3) 6 (60.0) 0 (0.0)   No known stage 9 5 (15.6) 2 (11.8) 1 (10.0) 1 (25.0)  Tumor anatomical side   Anterior–posterior 1 0 (0.0) 1 (5.9) 0 (0.0) 0 (0.0) 0.612   Left 3 2 (6.3) 0 (0.0) 1 (10.0) 0 (0.0)   Other 27 13 (40.6) 6 (35.3) 6 (60.0) 2 (50.0)   Not found 32 17 (53.1) 10 (58.8) 3 (30.0) 2 (50.0)  Recurrence   Yes 12 5 (15.6) 5 (29.4) 1 (10.0) 1 (25.0) 0.493   No 51 27 (84.4) 12 (70.6) 9 (90.0) 3 (75.0)  Adverse events   Yes 27 15 (46.9) 6 (35.3) 4 (40.0) 2 (50.0) 0.876   No 36 17 (53.1) 11 (64.7) 6 (60.0) 2 (50.0)  Survival status   Alive 32 18 (56.3) 7 (41.2) 5 (50.0) 2 (50.0) 0.784   Dead of disease 26 12 (37.5) 7 (41.2) 5 (50.0) 2 (50.0)   Not found 5 2 (6.3) 3 (17.6) 0 (0.0) 0 (0.0) fisher’s exact test Table 7 The association of clinico-pathological characteristics of endometrial cancer patients with ABO blood groups Blood group Endometrial Cancer Patients O A B AB p Total n  = 149 % n  = 81 % n  = 43 % n  = 10 % Tumor type  Tumor type Adenocarcinoma   Yes 158 77 (51.7) 46 (56.8) 29 (67.4) 6 (60.0) 0.322*   No 125 72 (48.3) 35 (43.2) 14 (32.6) 4 (40.0)  Tumor type Squamous cell carcinoma(SCC)   Yes 4 1 (.7) 2 (2.5) 1 (2.3) 0 (0.0) 0.461†   No 279 148 (99.3) 79 (97.5) 42 (97.7) 10 (100.0)  Tumor type Carcino-sarcoma (MMMT)   Yes 20 12 (8.1) 7 (8.6) 1 (2.3) 0 (0.0) 0.430*   No 263 137 (91.9) 74 (91.4) 42 (97.7) 10 (100.0)  Tumor type Adenosarcoma   Yes 7 4 (2.7) 2 (2.5) 1 (2.3) 0 (0.0)  > 0.99†   No 276 145 (97.3) 79 (97.5) 42 (97.7) 10 (100.0)  Tumor type Adeno-squamous-carcinoma   Yes 2 1 (.7) 1 (1.2) 0 (0.0) 0 (0.0)  > 0.99†   No 281 148 (99.3) 80 (98.8) 43 (100.0) 10 (100.0)  Tumor type sarcoma   Yes 13 7 (4.7) 4 (4.9) 1 (2.3) 1 (10.0) 0.636†   No 270 142 (95.3) 77 (95.1) 42 (97.7) 9 (90.0)  Tumor type carcinoid   Yes 1 1 (.7) 0 (0.0) 0 (0.0) 0 (0.0)  > 0.99†   No 282 148 (99.3) 81 (100.0) 43 (100.0) 10 (100.0)  Tumor type carcinoma   Yes 81 44 (29.5) 23 (28.4) 11 (25.6) 3 (30.0) 0.966*   No 202 105 (70.5) 58 (71.6) 32 (74.4) 7 (70.0) Histology Tumor  Histology serous   Yes 51 26 (17.4) 13 (16.0) 12 (27.9) 0 (0.0) 0.152*   No 232 123 (82.6) 68 (84.0) 31 (72.1) 10 (100.0)  Histology Endometrioid   Yes 185 94 (63.1) 57 (70.4) 25 (58.1) 9 (90.0) 0.178*   No 98 55 (36.9) 24 (29.6) 18 (41.9) 1 (10.0)  Histology Mucinous   Yes 4 2 (1.3) 1 (1.2) 0 (0.0) 1 (10.0) 0.178†   No 279 147 (98.7) 80 (98.8) 43 (100.0) 9 (90.0)  Histology clear cell   Yes 12 7 (4.7) 3 (3.7) 2 (4.7) 0 (0.0)  > 0.99†   No 271 142 (95.3) 78 (96.3) 41 (95.3) 10 (100.0)  Histology Neuro-endocrine   Yes 1 1 (.7) 0 (0.0) 0 (0.0) 0 (0.0)  > 0.99†   No 282 148 (99.3) 81 (100.0) 43 (100.0) 10 (100.0)  Histology Epithelial   Yes 11 6 (4.0) 4 (4.9) 1 (2.3) 0 (0.0) 0.891†   No 272 143 (96.0) 77 (95.1) 42 (97.7) 10 (100.0)  Histology Mixed/unknown/other   Yes 48 28 (18.8) 10 (12.3) 9 (20.9) 1 (10.0) 0.493*   No 235 121 (81.2) 71 (87.7) 34 (79.1) 9 (90.0)  TNM stage T   T1 147 76 (51.0) 42 (51.9) 23 (53.5) 6 (60.0) 0.338†   T2 28 12 (8.1) 14 (17.3) 2 (4.7) 0 (0.0)   T3 31 18 (12.1) 6 (7.4) 6 (14.0) 1 (10.0)   T4 1 0 (0.0) 0 (0.0) 1 (2.3) 0 (0.0)   Not found 76 43 (28.9) 19 (23.5) 11 (25.6) 3 (30.0)  TNM stage N   N0 55 27 (18.1) 18 (22.2) 9 (20.9) 1 (10.0) 0.559†   N1 15 7 (4.7) 6 (7.4) 2 (4.7) 0 (0.0)   N2 1 0 (0.0) 0 (0.0) 0 (0.0) 1 (10.0)   Nx 144 76 (51.0) 38 (46.9) 24 (55.8) 6 (60.0)   Not found 68 39 (26.2) 19 (23.5) 8 (18.6) 2 (20.0)  TNM Stage   M0 69 33 (22.1) 25 (30.9) 9 (20.9) 2 (20.0) 0.850†   M1 26 15 (10.1) 5 (6.2) 5 (11.6) 1 (10.0)   Mx 125 68 (45.6) 32 (39.5) 21 (48.8) 4 (40.0)   Not found 63 33 (22.1) 19 (23.5) 8 (18.6) 3 (30.0)  Tumor grade   G1 79 44 (29.5) 17 (21.0) 15 (34.9) 3 (30.0) 0.207†   G2 73 34 (22.8) 28 (34.6) 7 (16.3) 4 (40.0)   G3 102 51 (34.2) 29 (35.8) 19 (44.2) 3 (30.0)   Not found 29 20 (13.4) 7 (8.6) 2 (4.7) 0 (0.0)  FIGO Stage   Stage I 150 79 (54.1) 42 (54.5) 23 (54.8) 6 (60.0) 0.361†   Stage II 23 8 (5.5) 11 (14.3) 2 (4.8) 2 (20.0)   Stage III 37 25 (17.1) 5 (6.5) 6 (14.3) 1 (10.0)   Stage IV 27 13 (8.9) 9 (11.7) 5 (11.9) 0 (0.0)   No known stage 38 21 (14.4) 10 (13.0) 6 (14.3) 1 (10.0)  Tumor anatomical side   Anterior 10 5 (3.4) 4 (4.9) 0 (0.0) 1 (10.0) 0.770†   Posterior 5 1 (.7) 3 (3.7) 1 (2.3) 0 (0.0)   Anterior–posterior 46 24 (16.1) 12 (14.8) 8 (18.6) 2 (20.0)   Left 3 2 (1.3) 0 (0.0) 1 (2.3) 0 (0.0)   Right 4 2 (1.3) 1 (1.2) 1 (2.3) 0 (0.0)   Bilateral 7 2 (1.3) 3 (3.7) 1 (2.3) 1 (10.0)   Other 83 41 (27.5) 27 (33.3) 11 (25.6) 4 (40.0)   Not found 125 72 (48.3) 31 (38.3) 20 (46.5) 2 (20.0)  Recurrence   Yes 39 20 (13.4) 11 (13.6) 5 (11.6) 3 (30.0) 0.494*   No 244 129 (86.6) 70 (86.4) 38 (88.4) 7 (70.0)  Adverse events   Yes 118 61 (40.9) 34 (42.0) 17 (39.5) 6 (60.0) 0.683*   No 165 88 (59.1) 47 (58.0) 26 (60.5) 4 (40.0)  Survival status   Alive 194 106 (71.1) 55 (67.9) 28 (65.1) 5 (50.0) 0.510*   Dead of disease 89 43 (28.9) 26 (32.1) 15 (34.9) 5 (50.0) * chi-squared test † fisher’s exact test Table 8 The association of clinico-pathological characteristics of ovarian cancer patients with ABO blood groups Blood group Ovarian Cancer Patients O A B AB p Total n  = 60 % n  = 29 % n  = 20 % n  = 5 % Tumor type  Tumor type Adenocarcinoma   Yes 35 16 (26.7) 9 (31.0) 8 (40.0) 2 (40.0) 0.688*   No 79 44 (73.3) 20 (69.0) 12 (60.0) 3 (60.0)  Tumor type Squamous cell carcinoma(SCC)   Yes 2 2 (3.3) 0 (0.0) 0 (0.0) 0 (0.0)  > 0.99†   No 112 58 (96.7) 29 (100.0) 20 (100.0) 5 (100.0)  Tumor type Carcino-sarcoma (MMMT)   Yes 2 1 (1.7) 1 (3.4) 0 (0.0) 0 (0.0) 0.725†   No 112 59 (98.3) 28 (96.6) 20 (100.0) 5 (100.0)  Tumor type Adenosarcoma   Yes 1 1 (1.7) 0 (0.0) 0 (0.0) 0 (0.0)  > 0.99†   No 113 59 (98.3) 29 (100.0) 20 (100.0) 5 (100.0)  Tumor type sarcoma   Yes 2 1 (1.7) 0 (0.0) 1 (5.0) 0 (0.0) 0.455†   No 112 59 (98.3) 29 (100.0) 19 (95.0) 5 (100.0)  Tumor type carcinoma   Yes 48 23 (38.3) 16 (55.2) 6 (30.0) 3 (60.0) 0.237*   No 66 37 (61.7) 13 (44.8) 14 (70.0) 2 (40.0)  Tumor type Granulosacell Tumor   Yes 5 5 (8.3) 0 (0.0) 0 (0.0) 0 (0.0) 0.355†   No 109 55 (91.7) 29 (100.0) 20 (100.0) 5 (100.0) Histology Tumor  Histology serous   Yes 55 29 (48.3) 14 (48.3) 9 (45.0) 3 (60.0) 0.948*   No 59 31 (51.7) 15 (51.7) 11 (55.0) 2 (40.0)  Histology Endometrioid   Yes 3 1 (1.7) 1 (3.4) 1 (5.0) 0 (0.0) 0.639†   No 111 59 (98.3) 28 (96.6) 19 (95.0) 5 (100.0)  Histology Mucinous   Yes 13 5 (8.3) 4 (13.8) 3 (15.0) 1 (20.0) 0.491†   No 101 55 (91.7) 25 (86.2) 17 (85.0) 4 (80.0)  Histology clear cell   Yes 3 1 (1.7) 1 (3.4) 1 (5.0) 0 (0.0) 0.639†   No 111 59 (98.3) 28 (96.6) 19 (95.0) 5 (100.0)  Histology Epithelial   Yes 15 8 (13.3) 4 (13.8) 1 (5.0) 2 (40.0) 0.251†   No 99 52 (86.7) 25 (86.2) 19 (95.0) 3 (60.0)  Histology Mixed/unknown/other   Yes 29 16 (26.7) 6 (20.7) 6 (30.0) 1 (20.0) 0.876*   No 85 44 (73.3) 23 (79.3) 14 (70.0) 4 (80.0)  TNM stage T   T1 21 12 (20.0) 5 (17.2) 3 (15.0) 1 (20.0) 0.750†   T2 11 6 (10.0) 3 (10.3) 1 (5.0) 1 (20.0)   T3 21 9 (15.0) 8 (27.6) 3 (15.0) 1 (20.0)   Tx 1 0 (0.0) 1 (3.4) 0 (0.0) 0 (0.0)   Not found 60 33 (55.0) 12 (41.4) 13 (65.0) 2 (40.0)  TNM stage N   N0 19 9 (15.0) 6 (20.7) 3 (15.0) 1 (20.0) 0.173†   N1 7 4 (6.7) 0 (0.0) 2 (10.0) 1 (20.0)   Nx 25 11 (18.3) 11 (37.9) 2 (10.0) 1 (20.0)   Not found 63 36 (60.0) 12 (41.4) 13 (65.0) 2 (40.0)  TNM Stage   M0 31 13 (21.7) 13 (44.8) 4 (20.0) 1 (20.0) 0.167†   M1 7 3 (5.0) 0 (0.0) 3 (15.0) 1 (20.0)   Mx 11 7 (11.7) 3 (10.3) 1 (5.0) 0 (0.0)   Not found 65 37 (61.7) 13 (44.8) 12 (60.0) 3 (60.0)  Tumor grade   G1 6 2 (3.3) 2 (6.9) 2 (10.0) 0 (0.0) 0.782†   G2 8 4 (6.7) 4 (13.8) 0 (0.0) 0 (0.0)   G3 58 31 (51.7) 14 (48.3) 10 (50.0) 3 (60.0)   Not found 42 23 (38.3) 9 (31.0) 8 (40.0) 2 (40.0)  FIGO Stage   Stage I 22 12 (20.0) 6 (20.7) 3 (15.0) 1 (20.0) 0.790†   Stage II 2 1 (1.7) 1 (3.4) 0 (0.0) 0 (0.0)   Stage III 50 26 (43.3) 15 (51.7) 6 (30.0) 3 (60.0)   Stage IV 19 9 (15.0) 4 (13.8) 6 (30.0) 0 (0.0)   No known stage 21 12 (20.0) 3 (10.3) 5 (25.0) 1 (20.0)  Tumor anatomical side   Anterior 1 0 (0.0) 0 (0.0) 1 (5.0) 0 (0.0) 0.548†   Posterior 1 1 (1.7) 0 (0.0) 0 (0.0) 0 (0.0)   Anterior–posterior 1 0 (0.0) 0 (0.0) 0 (0.0) 1 (20.0)   Left 21 11 (18.3) 4 (13.8) 5 (25.0) 1 (20.0)   Right 22 10 (16.7) 8 (27.6) 3 (15.0) 1 (20.0)   Bilateral 38 20 (33.3) 12 (41.4) 5 (25.0) 1 (20.0)   Other 2 2 (3.3) 0 (0.0) 0 (0.0) 0 (0.0)   Not found 28 16 (26.7) 5 (17.2) 6 (30.0) 1 (20.0)  Recurrence   Yes 20 13 (21.7) 4 (13.8) 0 (0.0) 3 (60.0) 0.008†   No 94 47 (78.3) 25 (86.2) 20 (100.0) 2 (40.0)  Adverse events   Yes 52 30 (50.0) 11 (37.9) 7 (35.0) 4 (80.0) 0.217*   No 62 30 (50.0) 18 (62.1) 13 (65.0) 1 (20.0)  Survival status   Alive 62 32 (53.3) 18 (62.1) 11 (55.0) 1 (20.0) 0.366†   Dead of disease 40 21 (35.0) 10 (34.5) 7 (35.0) 2 (40.0)   Not found 12 7 (11.7) 1 (3.4) 2 (10.0) 2 (40.0) * chi-squared test † fisher’s exact test Table 9 The association of clinico-pathological characteristics of fallopian tube cancer patients with ABO blood groups Blood group Fallopian Tube Cancer Patients O A B AB p Total n  = 10 % n  = 11 % n  = 8 % n  = 2 % Tumor type  Tumor type Adenocarcinoma   Yes 13 5 (50.0) 3 (27.3) 4 (50.0) 1 (50.0) 0.691   No 18 5 (50.0) 8 (72.7) 4 (50.0) 1 (50.0)  Tumor type Carcino-sarcoma (MMMT)   Yes 1 0 (0.0) 1 (9.1) 0 (0.0) 0 (0.0)  > 0.99   No 30 10 (100.0) 10 (90.9) 8 (100.0) 2 (100.0)  Tumor type carcinoma   Yes 16 6 (60.0) 6 (54.5) 3 (37.5) 1 (50.0) 0.857   No 15 4 (40.0) 5 (45.5) 5 (62.5) 1 (50.0) Histology Tumor  Histology serous   Yes 20 7 (70.0) 4 (36.4) 7 (87.5) 2 (100.0) 0.085   No 11 3 (30.0) 7 (63.6) 1 (12.5) 0 (0.0)  Histology Endometrioid   Yes 2 1 (10.0) 1 (9.1) 0 (0.0) 0 (0.0)  > 0.99   No 29 9 (90.0) 10 (90.9) 8 (100.0) 2 (100.0)  Histology Mucinous   Yes 1 0 (0.0) 1 (9.1) 0 (0.0) 0 (0.0)  > 0.99   No 30 10 (100.0) 10 (90.9) 8 (100.0) 2 (100.0)  Histology clear cell   Yes 2 2 (20.0) 0 (0.0) 0 (0.0) 0 (0.0) 0.284   No 29 8 (80.0) 11 (100.0) 8 (100.0) 2 (100.0)  Histology Epithelial   Yes 2 0 (0.0) 1 (9.1) 1 (12.5) 0 (0.0) 0.763   No 29 10 (100.0) 10 (90.9) 7 (87.5) 2 (100.0)  Histology Mixed/unknown/other   Yes 8 3 (30.0) 5 (45.5) 0 (0.0) 0 (0.0) 0.129   No 23 7 (70.0) 6 (54.5) 8 (100.0) 2 (100.0)  TNM stage T   T1 4 3 (30.0) 0 (0.0) 1 (12.5) 0 (0.0) 0.553   T2 1 0 (0.0) 1 (9.1) 0 (0.0) 0 (0.0)   T3 10 3 (30.0) 5 (45.5) 2 (25.0) 0 (0.0)   Not found 16 4 (40.0) 5 (45.5) 5 (62.5) 2 (100.0)  TNM stage N   N0 1 0 (0.0) 0 (0.0) 1 (12.5) 0 (0.0) 0.218   N1 3 1 (10.0) 0 (0.0) 1 (12.5) 1 (50.0)   N2 1 1 (10.0) 0 (0.0) 0 (0.0) 0 (0.0)   Nx 11 5 (50.0) 5 (45.5) 1 (12.5) 0 (0.0)   Not found 15 3 (30.0) 6 (54.5) 5 (62.5) 1 (50.0)  TNM Stage   M0 1 0 (0.0) 0 (0.0) 0 (0.0) 1 (50.0) 0.154   M1 2 0 (0.0) 0 (0.0) 2 (25.0) 0 (0.0)   Mx 9 4 (40.0) 4 (36.4) 1 (12.5) 0 (0.0)   Not found 19 6 (60.0) 7 (63.6) 5 (62.5) 1 (50.0)  Tumor grade   G1 1 0 (0.0) 1 (9.1) 0 (0.0) 0 (0.0) 0.961   G2 1 1 (10.0) 0 (0.0) 0 (0.0) 0 (0.0)   G3 24 8 (80.0) 8 (72.7) 6 (75.0) 2 (100.0)   Not found 5 1 (10.0) 2 (18.2) 2 (25.0) 0 (0.0)  FIGO Stage   Stage I 2 0 (0.0) 0 (0.0) 1 (12.5) 1 (50.0) 0.214   Stage II 1 1 (10.0) 0 (0.0) 0 (0.0) 0 (0.0)   Stage III 14 5 (50.0) 7 (63.6) 2 (25.0) 0 (0.0)   Stage IV 6 1 (10.0) 3 (27.3) 2 (25.0) 0 (0.0)   No known stage 8 3 (30.0) 1 (9.1) 3 (37.5) 1 (50.0)  Tumor anatomical side   Left 1 0 (0.0) 1 (9.1) 0 (0.0) 0 (0.0) 0.963   Right 3 2 (20.0) 0 (0.0) 1 (12.5) 0 (0.0)   Bilateral 19 6 (60.0) 7 (63.6) 4 (50.0) 2 (100.0)   Other 3 1 (10.0) 1 (9.1) 1 (12.5) 0 (0.0)   Not found 5 1 (10.0) 2 (18.2) 2 (25.0) 0 (0.0)  Recurrence   Yes 8 2 (20.0) 3 (27.3) 2 (25.0) 1 (50.0) 0.930   No 23 8 (80.0) 8 (72.7) 6 (75.0) 1 (50.0)  Adverse events   Yes 22 3 (30.0) 10 (90.9) 7 (87.5) 2 (100.0) 0.006   No 9 7 (70.0) 1 (9.1) 1 (12.5) 0 (0.0)  Survival status   Alive 10 7 (70.0) 1 (9.1) 1 (12.5) 1 (50.0) 0.006   Dead of disease 17 2 (20.0) 9 (81.8) 6 (75.0) 0 (0.0)   Not found 4 1 (10.0) 1 (9.1) 1 (12.5) 1 (50.0) fisher’s exact test Table 10 The association of clinico-pathological characteristics of vaginal/vulval cancer patients with ABO blood groups Blood group Vagina/Vulva Cancer Patients O A B AB p Total n = 9 % n = 2 % n = 1 % n = 2 % Tumor type  Tumor type Adenocarcinoma   Yes 3 3 (33.3) 0 (0.0) 0 (0.0) 0 (0.0)  > 0.99   No 11 6 (66.7) 2 (100.0) 1 (100.0) 2 (100.0)  Tumor type Squamous cell carcinoma(SCC)   Yes 5 2 (22.2) 2 (100.0) 0 (0.0) 1 (50.0) 0.131   No 9 7 (77.8) 0 (0.0) 1 (100.0) 1 (50.0)  Tumor type sarcoma   Yes 2 2 (22.2) 0 (0.0) 0 (0.0) 0 (0.0)  > 0.99   No 12 7 (77.8) 2 (100.0) 1 (100.0) 2 (100.0)  Tumor type carcinoma   Yes 2 1 (11.1) 0 (0.0) 0 (0.0) 1 (50.0) 0.604   No 12 8 (88.9) 2 (100.0) 1 (100.0) 1 (50.0) Histology Tumor  Histology Endometrioid   Yes 4 4 (44.4) 0 (0.0) 0 (0.0) 0 (0.0) 0.520   No 10 5 (55.6) 2 (100.0) 1 (100.0) 2 (100.0)  Histology Epithelial   Yes 4 1 (11.1) 2 (100.0) 0 (0.0) 1 (50.0) 0 . 059   No 10 8 (88.9) 0 (0.0) 1 (100.0) 1 (50.0)  Histology Mixed/unknown/other   Yes 3 2 (22.2) 0 (0.0) 0 (0.0) 1 (50.0) 0.769   No 11 7 (77.8) 2 (100.0) 1 (100.0) 1 (50.0)  TNM stage T   T1 2 0 (0.0) 2 (100.0) 0 (0.0) 0 (0.0) 0.040   T3 2 2 (22.2) 0 (0.0) 0 (0.0) 0 (0.0)   T4 1 0 (0.0) 0 (0.0) 0 (0.0) 1 (50.0)   Not found 9 7 (77.8) 0 (0.0) 1 (100.0) 1 (50.0)  TNM stage N   N1 2 1 (11.1) 1 (50.0) 0 (0.0) 0 (0.0) 0.220   N2 1 0 (0.0) 0 (0.0) 0 (0.0) 1 (50.0)   Nx 2 1 (11.1) 1 (50.0) 0 (0.0) 0 (0.0)   Not found 9 7 (77.8) 0 (0.0) 1 (100.0) 1 (50.0)  TNM Stage   M1 3 1 (11.1) 1 (50.0) 0 (0.0) 1 (50.0) 0.253   Mx 2 1 (11.1) 1 (50.0) 0 (0.0) 0 (0.0)   Not found 9 7 (77.8) 0 (0.0) 1 (100.0) 1 (50.0)  Tumor grade   G1 2 1 (11.1) 1 (50.0) 0 (0.0) 0 (0.0) 0.346   G2 2 1 (11.1) 1 (50.0) 0 (0.0) 0 (0.0)   G3 6 4 (44.4) 0 (0.0) 0 (0.0) 2 (100.0)   Not found 4 3 (33.3) 0 (0.0) 1 (100.0) 0 (0.0)  FIGO Stage   Stage I 2 0 (0.0) 2 (100.0) 0 (0.0) 0 (0.0) 0.242   Stage II 1 1 (11.1) 0 (0.0) 0 (0.0) 0 (0.0)   Stage III 2 2 (22.2) 0 (0.0) 0 (0.0) 0 (0.0)   Stage IV 2 2 (22.2) 0 (0.0) 0 (0.0) 0 (0.0)   No known stage 7 4 (44.4) 0 (0.0) 1 (100.0) 2 (100.0)  Tumor anatomical side   Anterior 1 1 (11.1) 0 (0.0) 0 (0.0) 0 (0.0) 0.537   Anterior–posterior 1 1 (11.1) 0 (0.0) 0 (0.0) 0 (0.0)   Left 1 0 (0.0) 1 (50.0) 0 (0.0) 0 (0.0)   Right 2 1 (11.1) 1 (50.0) 0 (0.0) 0 (0.0)   Bilateral 2 2 (22.2) 0 (0.0) 0 (0.0) 0 (0.0)   Other 4 2 (22.2) 0 (0.0) 0 (0.0) 2 (100.0)   Not found 3 2 (22.2) 0 (0.0) 1 (100.0) 0 (0.0)  Recurrence   Yes 6 4 (44.4) 1 (50.0) 0 (0.0) 1 (50.0)  > 0.99   No 8 5 (55.6) 1 (50.0) 1 (100.0) 1 (50.0)  Adverse events   Yes 8 6 (66.7) 1 (50.0) 0 (0.0) 1 (50.0) 0.832   No 6 3 (33.3) 1 (50.0) 1 (100.0) 1 (50.0)  Survival status   Alive 8 4 (44.4) 1 (50.0) 1 (100.0) 2 (100.0) 0.933   Dead of disease 4 3 (33.3) 1 (50.0) 0 (0.0) 0 (0.0)   Not found 2 2 (22.2) 0 (0.0) 0 (0.0) 0 (0.0) fisher’s exact test Table 11 The association of clinico-pathological characteristics of mixed cancer patients with ABO blood groups Blood group Mixed Cancer Patients O A B AB p Total n  = 9 % n  = 8 % n  = 9 % n  = 1 % Tumor type  Tumor type Adenocarcinoma   Yes 9 4 (44.4) 3 (37.5) 2 (22.2) 0 (0.0) 0.789   No 18 5 (55.6) 5 (62.5) 7 (77.8) 1 (100.0)  Tumor type Squamous cell carcinoma(SCC)   Yes 3 0 (0.0) 2 (25.0) 1 (11.1) 0 (0.0) 0.360   No 24 9 (100.0) 6 (75.0) 8 (88.9) 1 (100.0)  Tumor type Carcino-sarcoma (MMMT)   Yes 2 1 (11.1) 0 (0.0) 1 (11.1) 0 (0.0)  > 0.99   No 25 8 (88.9) 8 (100.0) 8 (88.9) 1 (100.0)  Tumor type sarcoma   Yes 3 0 (0.0) 2 (25.0) 1 (11.1) 0 (0.0) 0.360   No 24 9 (100.0) 6 (75.0) 8 (88.9) 1 (100.0)  Tumor type carcinoma   Yes 9 4 (44.4) 0 (0.0) 4 (44.4) 1 (100.0) 0.049   No 18 5 (55.6) 8 (100.0) 5 (55.6) 0 (0.0)  Tumor type Granulosacell Tumor   Yes 1 0 (0.0) 1 (12.5) 0 (0.0) 0 (0.0) 0.333   No 26 9 (100.0) 7 (87.5) 9 (100.0) 1 (100.0) Histology Tumor  Histology serous   Yes 10 3 (33.3) 0 (0.0) 6 (66.7) 1 (100.0) 0.013   No 17 6 (66.7) 8 (100.0) 3 (33.3) 0 (0.0)  Histology Endometrioid   Yes 10 3 (33.3) 4 (50.0) 3 (33.3) 0 (0.0) 0.859   No 17 6 (66.7) 4 (50.0) 6 (66.7) 1 (100.0)  Histology Mucinous   Yes 4 2 (22.2) 1 (12.5) 1 (11.1) 0 (0.0)  > 0.99   No 23 7 (77.8) 7 (87.5) 8 (88.9) 1 (100.0)  Histology clear cell   Yes 1 0 (0.0) 0 (0.0) 1 (11.1) 0 (0.0)  > 0.99   No 26 9 (100.0) 8 (100.0) 8 (88.9) 1 (100.0)  Histology Epithelial   Yes 2 0 (0.0) 1 (12.5) 1 (11.1) 0 (0.0) 0.769   No 25 9 (100.0) 7 (87.5) 8 (88.9) 1 (100.0)  Histology Mixed/unknown/other   Yes 11 4 (44.4) 2 (25.0) 5 (55.6) 0 (0.0) 0.598   No 16 5 (55.6) 6 (75.0) 4 (44.4) 1 (100.0)  TNM stage T   T1 3 2 (22.2) 0 (0.0) 1 (11.1) 0 (0.0) 0.162   T2 4 2 (22.2) 2 (25.0) 0 (0.0) 0 (0.0)   T3 6 1 (11.1) 2 (25.0) 3 (33.3) 0 (0.0)   T4 3 0 (0.0) 3 (37.5) 0 (0.0) 0 (0.0)   Not found 11 4 (44.4) 1 (12.5) 5 (55.6) 1 (100.0)  TNM stage N   N0 1 1 (11.1) 0 (0.0) 0 (0.0) 0 (0.0) 0.453   N1 2 1 (11.1) 1 (12.5) 0 (0.0) 0 (0.0)   N2 1 0 (0.0) 1 (12.5) 0 (0.0) 0 (0.0)   Nx 12 3 (33.3) 5 (62.5) 4 (44.4) 0 (0.0)   Not found 11 4 (44.4) 1 (12.5) 5 (55.6) 1 (100.0)  TNM Stage   M0 1 1 (11.1) 0 (0.0) 0 (0.0) 0 (0.0) 0.407   M1 6 1 (11.1) 4 (50.0) 1 (11.1) 0 (0.0)   Mx 6 1 (11.1) 2 (25.0) 3 (33.3) 0 (0.0)   Not found 14 6 (66.7) 2 (25.0) 5 (55.6) 1 (100.0)  Tumor grade   G1 2 1 (11.1) 0 (0.0) 1 (11.1) 0 (0.0) 0.836   G2 5 2 (22.2) 2 (25.0) 1 (11.1) 0 (0.0)   G3 17 5 (55.6) 4 (50.0) 7 (77.8) 1 (100.0)   Not found 3 1 (11.1) 2 (25.0) 0 (0.0) 0 (0.0)  FIGO Stage   Stage I 3 2 (22.2) 1 (12.5) 0 (0.0) 0 (0.0) 0.239   Stage II 5 2 (22.2) 2 (25.0) 1 (11.1) 0 (0.0)   Stage III 10 3 (33.3) 1 (12.5) 5 (55.6) 1 (100.0)   Stage IV 6 0 (0.0) 4 (50.0) 2 (22.2) 0 (0.0)   No known stage 3 2 (22.2) 0 (0.0) 1 (11.1) 0 (0.0)  Tumor anatomical side   Anterior 2 0 (0.0) 1 (12.5) 1 (11.1) 0 (0.0) 0.855   Anterior–posterior 2 0 (0.0) 1 (12.5) 1 (11.1) 0 (0.0)   Left 1 1 (11.1) 0 (0.0) 0 (0.0) 0 (0.0)   Right 3 1 (11.1) 2 (25.0) 0 (0.0) 0 (0.0)   Bilateral 9 2 (22.2) 3 (37.5) 3 (33.3) 1 (100.0)   Other 5 3 (33.3) 0 (0.0) 2 (22.2) 0 (0.0)   Not found 5 2 (22.2) 1 (12.5) 2 (22.2) 0 (0.0)  Recurrence   Yes 10 1 (11.1) 4 (50.0) 5 (55.6) 0 (0.0) 0.159   No 17 8 (88.9) 4 (50.0) 4 (44.4) 1 (100.0)  Adverse events   Yes 19 5 (55.6) 7 (87.5) 7 (77.8) 0 (0.0) 0.249   No 8 4 (44.4) 1 (12.5) 2 (22.2) 1 (100.0)  Survival status   Alive 9 5 (55.6) 0 (0.0) 3 (33.3) 1 (100.0) 0.081   Dead of disease 15 4 (44.4) 6 (75.0) 5 (55.6) 0 (0.0)   Not found 3 0 (0.0) 2 (25.0) 1 11.1) 0 0.0) fisher’s exact test The association of clinico-pathological characteristics of cervical cancer patients with ABO blood groups fisher’s exact test The association of clinico-pathological characteristics of endometrial cancer patients with ABO blood groups * chi-squared test † fisher’s exact test The association of clinico-pathological characteristics of ovarian cancer patients with ABO blood groups * chi-squared test † fisher’s exact test The association of clinico-pathological characteristics of fallopian tube cancer patients with ABO blood groups fisher’s exact test The association of clinico-pathological characteristics of vaginal/vulval cancer patients with ABO blood groups fisher’s exact test The association of clinico-pathological characteristics of mixed cancer patients with ABO blood groups fisher’s exact test In case of the patient dependent GCs, data analysis revealed a significant association between ovarian cancers and recurrence, fallopian tube cancers and adverse events and survival status, vaginal/vulval cancers and TNM stage and mixed GCs and tumor type (carcinoma). Furthermore, multinomial analysis between various confounding factors and GCs revealed that the risk of Cervical, Endometrial and Ovarian cancers to be significant for Type B BG ( P  < 0.05) (Table  12 ). Table 12 Multinomial analysis between confounding factors of all gynecological cancers and ABO blood groups Blood group B Wald OR 95% CI p A Age .00 .00 1.00 (.99 1.02) 0.970 BMI .04 2.63 1.04 (.99 1.09) 0.105 Underweight .66 .83 1.93 (.47 7.86) 0.361 Normal weight .28 .35 1.32 (.53 3.28) 0.553 Overweight -.06 .03 .95 (.48 1.88) 0.872 Obese 0 b Cervix -.56 .95 .57 (.18 1.76) 0.330 Endometrium -.66 1.62 .52 (.19 1.42) 0.203 Ovaries -.62 1.29 .54 (.19 1.56) 0.256 Vagina -1.40 2.26 .25 (.04 1.53) 0.133 Fallopian .14 .04 1.15 (.31 4.20) 0.833 Mix 0 b B Age .00 .05 1.00 (.98 1.02) 0.825 BMI .00 .00 1.00 (.94 1.06) 0.961 Underweight .84 1.12 2.32 (.49 11.02) 0.289 Normal weight -.04 .01 .96 (.31 2.93)) 0.938 Overweight -.20 .23 .82 (.36 1.87) 0.631 Obese 0 b Cervix -1.25 4.31 .29 (.09 .93) 0.038 Endometrium -1.29 6.26 .28 (.10 .76) 0.012 Ovaries -1.20 4.75 .30 (.10 .89) 0.029 Vagina -2.17 3.48 .11 (.01 1.12) 0.062 Fallopian -.31 .21 .73 (.19 2.77) 0.644 Mix 0 b AB Age .01 .73 1.01 (.98 1.05) 0.394 BMI -.05 .92 .95 (.85 1.06) 0.338 Underweight -1.28 .71 .28 (.01 5.47) 0.399 Normal weight -1.18 1.40 .31 (.04 2.17) 0.236 Overweight -1.50 3.61 .22 (.05 1.05) 0.057 Obese 0 b Cervix .04 .00 1.04 (.10 10.69) 0.976 Endometrium -.71 .40 .49 (.05 4.43) 0.526 Ovaries -.31 .07 .73 (.07 7.21) 0.790 Vagina .51 .14 1.66 (.12 23.24) 0.705 Fallopian .38 .08 1.47 (.11 19.75) 0.772 Mix 0 b Multinomial analysis between confounding factors of all gynecological cancers and ABO blood groups

Conclusion

In conclusion, our study demonstrated that Type O + BG to be most common among our population. Furthermore, among our patients, the most common cancer was and the rarest was vaginal/valval cancer. No significant association was found between the anatomical site, stage, complication, and survival status of all types of GCs. Furthermore, a significant association between BG type B was found with serous histology of endometrial and ovarian cancers, while BG type AB was associated with fallopian tube cancers. The recurrence rate in ovarian cancer patients was significantly associated with AB blood group. Multinomial analysis also revealed a significant association of BG type B with cervical, endometrial and ovarian cancers.

Discussion

ABO blood type is a major component of a patient's genetic makeup and is associated with various types of cancer [ 12 , 24 , 31 ]. Although previous studies have reported to establish blood group types as a major risk factor in contribution to cancer formation and its association with overall cancer risk remains debatable [ 12 , 13 , 17 – 20 ]. ABO blood group are the phenotypes of the two antigens A and B, on a polypeptide called H antigen which is the product of a single multi-exon ABO gene located on the chromosome 9q34.2. Antigen A and B are oligosaccharides, A being N-acetylgalactosamine (GalNAc) and B being galactose (Gal) and lack of expression of either antigen results in the O phenotype [ 31 ]. In our current study, the overall distribution of ABO blood group in gynecological cancer patients was found to be O > A > B > AB, the results were consistent with a local study that was conducted in Northern Asir region in Saudi Arabia [ 37 ] and few international [ 19 , 21 ]. Zhang et al., (2014) in their meta-analysis reported that the individuals having A blood type have a higher risk of cancer, while as the individuals having type O have decreased risk [ 14 ]. The vast majority of the dependent variables, such as FIGO stage, survival status and recurrence were not significantly associated with ABO blood group in endometrial cancer patients. However, we found a notable association between BG type B and the serous type of endometrial cancer, highlighting a unique pattern in the occurrence of this cancer subtype. Additionally, our research further revealed a remarkable association specifically between BG type B and serous histology type in fallopian tube cancer patients. This is particularly noteworthy as fallopian tube cancer is secondary to and shares histological characteristics with ovarian cancer [ 38 ]. Gates et al. (2011) in their retrospective study reported that that while blood group O was the most common, blood types of AB and B to be associated with a borderline significant increased risk of ovarian cancer [ 39 ]. The magnitude of the association was identical for BG type AB and type B, indicating that the B antigen may influence ovarian carcinogenesis. Several recent studies have investigated the role of ABO BG and EC; however, the reported results are often contradictory and do not show a consistent correlation [ 40 , 41 ]. A recent study also demonstrated that endometrial cancer patients with BG type A have lesser chance for developing poorly differentiated tumors [ 40 ]. Gitas et al. (2020) found no connection between the serous subtype and the grade or stage of endometrial cancer, nor any meaningful association between ABO blood types and these factors [ 41 ]. Another study also reported similar results that the BG distribution did not significantly differ among different tumor grades or subtypes, including EC and non-EC [ 19 ]. In an Iranian retrospective study, it was reported that, in breast cancer, O was the most common BG, followed by B, A, and AB; and in cervical cancer, A, B, and AB were the next most common blood groups. However, the study did not find any significant association with ABO and Rh BG [ 42 ]. Contrary to this, some Asian studies have reported that BG type B to be most common among their populations followed by O, A and AB [ 43 – 45 ], but no association with any cancers. In another study on esophageal cancer, Yang et al. found that individuals with blood type O had relatively poorer overall survival rates than those with non-O blood groups [ 46 ]. Nevertheless, it is important to note that our study did not find any association between survival status and the occurrence of fallopian tube cancer, adding a critical dimension to the understanding of these malignancies. Current understanding suggests a potential link between ABO BG antigens and cancer, via elicitation of the inflammatory pathway molecules that impacts cancer development and progression [ 32 , 47 – 49 ]. The ABO gene locus, and the genetic variations thereof, has been linked to circulating amounts of inflammatory mediators such as tumor necrosis factor-alpha (TNF-α), soluble intercellular adhesion molecule (ICAM)−1, E-selectin, and P-selectin, which are vital for immune cell recruitment [ 50 – 52 ]. ABO BG antigens are major histocompatibility (MHC) antigens, indicating a possible role in influencing immune responses to cancer cells [ 53 ]. Additionally, these proteins, along with TNF-α, are key players in mediating systemic inflammatory responses [ 54 , 55 ]. Chronic inflammation, which can be altered by blood type, is associated with different stages of tumor growth, including cellular transformation, promotion, survival, proliferation, invasion, angiogenesis, and metastasis [ 56 , 57 ]. Additionally, non-O BGs, particularly BG A, have significantly reduced expression of soluble ICAM-1 compared to blood group O; which may promote metastatic spread of tumors, as cancer cells use similar adhesion mechanisms [ 32 ]. Furthermore, our study found a significant association between recurrence rates in OC and AB blood group. This was in tune with the previous study, which found no significant correlation between ABO BGs and the survival rate [ 58 ]. A previous study found that ABO BG to be associated with survival rate among OC patients and reported that non-A blood group patients had significantly better survival rate than A blood group patients [ 29 ]. However, in another retrospective study on ovarian cancer (OC), patients with B blood type showed a better overall survival (OS) compared with non-B blood- type patients, suggesting a role of B antigen in the susceptibility of cancer initiation and progression [ 59 ]. It is critical to remember that all these ABO blood types, and cancer associations should not be interpreted as definitive risk factors. It is also important to know that the link between ABO blood type and cancer is an ongoing field, but definitive causality has not yet been established and the mechanism is still unknown [ 33 ]. Having a certain blood type does not mean you will get or be immune to cancer. In fact, cancer risk is influenced and increased by a complex interaction of genetic and environmental factors which are smoking, gene mutations, obesity, and hormonal factors [ 60 ]. Conversely, our study has found no significant association between the risk of relapse in valvular cancer and BG type. Montavon et al. (2018), reported that patients with BG O and B showed significantly increased risk for OC relapse compared to BG A – 59% for O and 82% for B [ 13 ]. Furthermore, patients with valvular cancer and blood group O have an increased risk of relapse compared to patients with BG type A. However, one study reported no significant impact of ABO blood type on progression-free survival or overall survival in epithelial ovarian cancer (EOC) patients [ 39 , 47 ]. Thus, ABO blood type status may be a predictive factor for relapse-free survival in ovarian and vulvar malignancies [ 13 ]; but clinical relevance of ABO blood groups in gynecological cancer prognosis remains questionable due to inconsistent findings across studies [ 13 , 39 , 47 , 61 ]. This study has potential limitations. First, it lacks generalisability as the study was carried out in only one oncology centre in the western region of the Kingdom. Thus, the results might not be applicable in a broader and different context. Furthermore, due to the retrospective nature of the study, the data had some irregularities in many parameters including the primary site of the cancers. Hence, there was an overlap on the tumour site. Hence, in future studies, it is recommended to include multiple cancer centres in different regions to achieve better contextual results, which are applicable to a broader population.

Introduction

Gynecological Cancer (GC) affects the female’s reproductive system and are categorized into five types depending on the organ affected—cervical, endometrial, ovarian, vaginal, and vulvar cancer [ 1 ]. GCs account for an approximately 15%, (1,398,601) of new cases among women worldwide in 2020, with the corresponding mortality rate of 48%. Cervical cancer is the second most prevalent type of GCs and fourth leading cause of cancer mortality in women [ 2 ]. In Saudi Arabia, GCs represent ~ 13.46% of all cancer incidence with 1836 new cases reported in 2020 [ 3 ]. Among GCs, the three commonest are cervical cancer (CC), endometrial cancer (EC) and ovarian cancer (OC) and account for more than one-third of the newly diagnosed cancers globally in females, while others are usually either secondary to these three or rare in etiology [ 4 ]. GCs pose a serious threat to women’s health because they are so difficult to detect and there is a lack of reliable early-stage screening or detection tools except for cervical cancer (CC). Symptoms of GCs, especially endometrial (EC) and ovarian cancer (OC), usually appear in advanced stages which result in high mortality rate and poor outcome [ 5 , 6 ]. Establishing cancer control and prognostic factors are important in estimating the impact of cancer in terms of incidence and mortality. Several research studied multiple prognostic aspects of some GCs [ 7 , 8 ]. Age, late menopause, obesity, and histological typing are important prognostic factors in endometrial cancer [ 9 ]. Small et al. (2017), reported that most high-grade cervical pre-cancers are caused by two human papillomavirus (HPV) types (16 and 18) [ 10 ]. In ovarian cancer, current literature identifies the ovulation cycles, genetic disposition, family history, and endometriosis as the major risk factors [ 11 ]. One important risk factor for all types of GCs is the ABO blood group (BG) system, which classifies human blood according to the antigen (A, B or both), which are present on glycosphingolipids found on erythrocytes cell surface [ 12 , 13 ]. ABO BG has been reported to have an association with certain types of cancers such as gastric and breast cancer [ 14 ]. In one of the sentinel meta-analysis, the A blood group was associated with an increased risk of gastric cancer compared to non-A blood types, while the O blood group was associated with a lower risk compared to non-O blood types; it is worth noting that patients with the A blood type were also at a higher risk of Heliobacter pylori infection [ 15 ]. It has also been reported that patients with blood type A faced twice the risk of developing pancreatic cancer in comparison to individuals with blood type O [ 16 ]. Furthermore, previous studies have indicated that individuals with blood types B and AB exhibit a significantly increased risk of esophageal squamous cell carcinoma (ESCC) compared to those with blood type O. Among these blood types, individuals with blood type AB are found to have the highest risk of developing ESCC [ 17 ]. Various studies across the world have reported, though not consistently, an association between the ABO BGs and incidence, prognosis, and clinicopathologic characteristics of numerous cancers [ 13 , 18 – 30 ]; but ABO BGs’ relationship, its usage as prognostic tool and role played in the development and progression of carcinogenesis is still an enigma for researchers [ 12 , 31 – 33 ]. Most of the previous research focused on the association between ABO blood groups and ovarian cancer and little is known about other types of GCs (cervical, endometrial, vaginal, vulvar) [ 26 ]. In addition, there is lack of in-depth research focused in the area featuring the role of various demographic factors like age, social background, and income, all of which plays a major role in morbidity and mortality rate. Although many studies globally demonstrated that ABO BGs were linked to various cancers, coupled with the fact that only a few studies have been carried out, in the past decade, to explore the association of ABO antigens with the susceptibility of various cancers [ 34 – 36 ], there is still much to explore. Since there is a dearth of epidemiological data on GCs from the MENA region especially from Saudi Arabia, research to explore the link between ABO blood group linked susceptibility to GCs is still warranted. Therefore, our aim was to investigate the association of GCs with the ABO BGs in Saudi population. The findings of this study will improve cancer prevention, detection, and treatment as well as guide the way to better diagnosis and treatment by investigating the association of GCs with the ABO blood group.

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