Evaluation of Relationship between ABO bloods with Oral Cancer and Compared with Healthy Individuals
RaziyehsadatRezvaninejad1, HesamZiaadini2, RayehehossadatRezvaninejad3*
1Department of Oral Medicine, Faculty of Dentistry, HormozganUniversity of Medical Sciences, Hormozgan, Iran
2Student Research Committee, Faculty of Dentistry, HormozganUniversity of Medical Sciences, Hormozgan, Iran
3Dental Clinic of Bandar Abbas School of Dentistry, ShahidNaser St, Imam Khomeini Blvd, Bandar Abbas, Hormozgan, Iran
* Email: [email protected], Tel: +98 913 242 0499
Abstract
Objective: In Iran, due to the increased risk factors for oral cancer, the prevalence of this disease is increasing. Genetic factors such as ABO blood types may influence the severity and the incidence of oral cancer. This study aimed to investigate the relationship between ABO blood groups and oral cancer and compare it with healthy individuals.
Study Design: In this case-control study, 64 patients with oral cancer were compared with 60 healthy controls in terms of ABO blood groups. Data were collected using a checklist prepared from patients' records which included demographic information, blood group and Rh status information and clinical information, pathology report, lesion information and smoking habits. Data were analyzed by independent t-test, chi-square and one-way analysis of variance.
Results: The mean age of patients with oral cancer was 58.73 ± 14.06. Among the patients, 56.3% were male, and 43.8% were female. The frequency of male smokers was significantly higher than female smokers. The distribution of smoking was significantly higher in patients than the control group (P <0.001). The prevalence of blood group A in patients with oral cancer was significantly higher than the control group (P = 0.034). The difference in Rh frequency between patients and the control group was not statistically significant.
Conclusion: The presence of antigen A on cells may increase the risk of oral cancer according to our study, while blood type O was less common in these patients.
Keywords: Oral cancer, ABO blood group, Rh, OSCC
INTRODUCTION
Oral cancers include a broad spectrum of malignant neoplasms which develop inside the mouth. Tumors on lips, tongue, gum, the floor of the mouth, hard and soft palate, tonsils, salivary glands, oropharynx, nasopharynx, and hypopharynx are classified as the different types of oral cancers. Squamous cell carcinomas (SCCs) account for more than 90% of oral cancer cases. Approximately 9% of cancers include salivary gland carcinomas, sarcomas, and lymphomas, and the remaining 1% include metastatic cancers developed in lungs, breasts, prostate, and kidneys (1). The oral cancer incidence rate is rising. Due to population growth, enhanced life expectancy and increased exposure to risk factors, its prevalence is ever increasing. In our country, due to the increased exposure to risk factors, the prevalence of this disease is rising. In terms of the consequences of oral cancer, there is a growing need to develop programs for prevention, early diagnosis and thus improve the quality of life of affected people (2).Clinical manifestations of carcinomas in the mucosal surfaces of the oral cavity is varied. Tumors can be found in various forms including ulcers, prominent fungal- like masses, papilloma, warts, white plaques, red plaques, or a combination of white and red
plaques (3). A large number of primary oral cancers are asymptomatic, while advanced lesions are often scarred with a prominent, hard margin, and pain is often absent until the last stages of the disease (4). New studies suggest that blood type may be regarded as a marker of the higher risk for heart disease, Alzheimer disease and even cancer. People's blood type may affect their risk of developing diseases. However, the results of these studies are still under survey, and scientists have not yet managed to make a convincing conclusion about why blood types are associated with an increased incidence of certain diseases. Even though no one can change the blood type, knowing the potential risks can be helpful in prevention (5).
The ABO blood group system has been employed in most studies to investigate genetic factors. Genetic factors such as ABO blood types may affect the morbidity, severity, and incidence of some diseases (6). The association between blood types and various diseases such as cancers, diabetes mellitus, skin diseases, heart disease, genetic disorders, tooth decay and blood diseases has been surveyed (7, 8). Some of these studies have shown an increased relative risk for these diseases regarding blood groups, but the obtained results are not consistent (9). Due to the difference in the distribution of ABO genes and their possible association with the disease as well as due to this fact that few studies have been accomplished in this regard in the country, this study was conducted to investigate the association between ABO blood groups and oral cancer and compare the results with those of healthy individuals.
METHODS AND MATERIALS Study design
The present study is a case-control survey. In this study, all patients with oral squamous cell carcinoma (64 patients) at ShahidMohammadi Cancer Therapy Center in Bandar Abbas were selected by census and included in the study. Sixty healthy blood donors with no family history of oral cancer were randomly selected as the control group. Inclusion criteria included oral cancer based on histopathological examination of oral squamous cell carcinoma (OSCC) and patients with unknown malignancies were excluded.
Data were collected using a checklist provided from patients' records. This checklist consisted of three sections. The first part includes demographic information (age, gender) of patients, the second part includes information about blood groups and Rh status, and the third part includes clinical information, pathology report, information about the lesion including malignancy, lymphatic and bone invasion and smoking habit in patients. After obtaining the necessary permissions to collect data, first, all the records were reviewed, and the records of patients with malignancies in the mouth, jaw and face and surrounding tissues were chosen.
Cases without pathological confirmation were excluded from the study, and only patients whose pathology report included one of the several types of malignancies in the oral, maxillofacial, and surrounding tissues were evaluated. Then the necessary information was obtained and recorded in the provided checklist
Statistical analysis
Data were analyzed employing SPSS software as well as independent t-test, chi-square and one-way analysis of variance (ANOVA). A p-value less than 0.05 was considered as statistically significant.
RESULTS
In the current study, the blood type of 64 oral cancer patients were compared with the ones of 60 healthy individuals with no history of oral cancer. The average age of patients was measured to be 58.73 ±14.06 (23-84 years. It should be noted that 36 subjectswere male
±12.94 years and the mean age of female patients was calculated to be 58.16 ±15.60 years.
The observed difference was not statistically significant (P = 0.77).
The finding of our study revealed that the mean size of tumors in patients was 2.47 ±0.88 (4.78-1.13 cm). Furthermore,the mean tumor size in male patients was 2.45± 0.92, while the mean tumor size in female patients was 2.51± 0.83. Nonetheless, the difference was not statistically significant (p = 0.80). It was also found that 18 patients (1.28%) had lymphatic involvement and 5 patients (7.8%) had experienced invasion to bone tissue.
According to figure 1, the frequency of male patients smoking 10-20 cigarettes per day was higher than other cases and only 8.3% (3 people) of male patients did not smoke. 64.3% (18 patients) of female patients did not smoke and 7 patients (25%) smoked less than 10 cigarettes per day. The difference in the frequency distribution of smoking between male and female patients was statistically significant (P <0.001). According to figure 2, both women and men in the control group had a higher frequency of non-smokers than smokers. The percentage of men who smoked less than 10 cigarettes and 10-20 cigarettes was higher than women. This difference was not statistically significant (P = 0.07).
According to the results summarized in Table 1, the mean age of patients with oral cancer was higher than the mean age of healthy individuals. This difference was statistically significant. There was no statistically significant difference between the patient and control groups in terms of gender. The frequency of non-smokers in the control group was higher than the case group and also the frequency of patients who smoked 10-20 or more cigarettes was higher in the case groupcompared with the control group. Frequency differences between patient and control groups with respect to smoking were statistically significant. The results also showed that the percentage frequency of blood group A in cancer patients was higher than the control group. Other blood groups had a higher frequency in the control group compared with the case group. This difference was considered as statistically significant.
Moreover, the results of the table demonstrated that Rh + frequency in the control group was higher than the case group. This difference was not statistically significant.
Figure 1. Frequency distribution of smoking in patients based on gender.
6 7
14
2 13
1 3
18
0 2 4 6 8 10 12 14 16 18 20
Male Female
Less than 10 cigarette Between 10 to 20 cigarette
Figure 2. Frequency distribution of smoking in control group based on gender.
Table 1. Mean age difference, the frequency distribution of gender, smoking, the frequency distribution of blood and Rh groups in patient and control groups
Variable Subgroup Patient Control P-Value
Age 58.73±14.06 42.12±7.42 <0.001
Gender Male 36(56.3%) 33(55.0%)
0.88
Female 28(43.8%) 27(45.0%)
Smoking
Less than 10
cigarette 13(20.3%) 10(16.7%)
<0.001 Between 10 to
20 cigarette 16(25.0%) 4(6.7%) More than 20
cigarette 14(21.9%) 0
Non-Smoker 21(32.8%) 46(76.7%)
Rh Rh+ 54(84.4%) 52(86.7%)
0.71
Rh- 10(15.6%) 8(13.3%)
Blood type
A 23(35.9%) 8(13.6%)
0.034
B 15(23.4%) 20(33.9%)
AB 4(6.3%) 7(11.9%)
O 22(34.4%) 24(40.7%)
Figure 3 represents the frequency distribution of patients based on the location of the malignancy. According to the results, tongue (29.7%) followed by the alveolar ridge and vestibular mucosa (23.4%) were regarded as the most common malignant sites, whilethe lowest frequency was observed in the hard palate (7.8%).
7 7
4
2 22
18
0 5 10 15 20 25
Male Female
Less than 10 cigarette Between 10 to 20 cigarette Non-Smoker
Figure 3.Frequency distribution of patients based on the site of malignancy.
DISCUSSION
The findings of the current study indicated this fact that the frequency of A blood type was significantly higher in patients compared with the healthy subjects. It was also reported that the frequency of Rh+ in the case group was lower than the control group. Besides, Jalil BF pointed out that in comparison with other blood groups, people with A blood group are 1.46 times more susceptible to develope oral cancer, which was consistent with the results of the present study (10). Furthermore, Raghavan et al. showed an increase in A blood type susceptibility to oral cancer, which was similar to the present study (11). The results of Toto et al. (12) were consistent with the results of our study.
Nevertheless, contrary to the present study results, in the study of Sharma et al. (13) and Mortazavi et al. (14), the frequency of A blood type was significantly higher among patients with oral cancer. It is worth mentioning that, Deepak et al. (15) showed that the most common blood type in patients with oral cancer was blood type AB, while blood group O indicated the lowest frequency. Several other studies (16, 17) also showed that patients with A and B antigens had a higher incidence of oral cancer than healthy subjects. In the study of Mortazavi et al., just like the present study, the difference in Rh between case and control group was not statistically significant (14).
The high prevalence of some carcinomas in patients with A blood type may be attributed to the high dependence of some microorganisms on this antigen which leads to malignancy (18, 19). It is worth mentioning that people with A blood type are more susceptible to developing oral cancer. This can be explained by the fact that A antigens are found in the epithelial cells of other tissues, including the oral mucosa as well as in the erythrocyte membrane. The relative regulation of glycosyltransferase, which is involved in the biosynthesis of antigens A and B, is associated with tumor growth (18). Partial or complete elimination of epithelial blood group antigens resulting from abnormalities in their synthesis causes changes in their cell surface. This indicates that the antigen pattern changes at the cell surface of a tumor, and consequently result in malignancy (20). H antigen is a blood type antigen that is present in all people, regardless of blood type. It is a precursor of A and B antigens. In people with A and B blood groups, the progressive antigen H is converted to antigens A and B, respectively, while in people with blood groups O, it keeps its original form. People with blood type O have the highest H antigen levels, which plays a protective role against oral cancer.
Therefore, people with O blood type are less prone to oral cancer (21).
9
19
9
7
5
15
0 2 4 6 8 10 12 14 16 18 20
The site of malignancy
Lip Tongue
Gingiva Floor of the mouth
Hard palate Alveolar ridge and vestibular mucosa
The mean age of patients with oral cancer was significantly higher than the control group.
Furthermore, the mean age of male patients was higher than female patients. Oral cancer is mainly a disease associated with old age (22). The results of Chidzange et al.'s (23), Yaghoubi et al.'s (24), and Sargaran and Moradzadeh's studies were similar to our findings (25). In the study of Yaghoubi et al. (24), in agreement with the present study, male patients' mean age was higher than female patients. However, in the study of Arotibio et al. (26), the mean age of women was higher than men's mean age.
The frequency of male patients was higher than females, showing male-to-female ratio of 1.4 to 1. Similar to the present study in the study of Shiva and Moosavi (27), male-to-female ratio was 0.3 to 1, in the study of Jacobson et al. it was 1.7 to 1 and in the study of Al-Rawi and chidzange was 2 to 1, which was close to the present study (23, 29). Male-to-female ratio varies in various parts of the world. In a study conducted in Spain, 8.4 to 1 ratio was reported (30). In Iran, the ratio of 5 to 1 was reported in Fars province (31). In the study of Hosseinpour et al., The number of affected women was higher than men (32). A study in India demonstrated that men were more likely to have oral cancer than women (33). It should be mentioned that oral cancer is more common in men than in women. Interestingly, male-to- female ratio in 1950 was 6 to 1, while, today, it is measured to be less than 2 to 1 (34).
Smoking was an effective factor in causing cancer so that the frequency of smokers in the patient group was higher than the control group, and also the frequency of patients who smoked 10-20 or more cigarettes in the patient group was significantly higher than the control group. It was also reported that the risk of oral cancer in smokers is twice as high as that in non-smokers. Banokzi concluded in a study that tobacco consumption plays an important role in the development of oral cancer and leukoplakia (35). Evidence suggests that smoking is an effective factor in the development of leukoplakia and squamous cell carcinoma (36). Some studies report a similar risk of cancer in smokers and hookah users, and other researchers report a greater adverse effect of hookah users on the oral mucosa compared with cigarette smokers (37-50).
The present study results showed that the most common affected site was located on tongue (29.7%), followed by the alveolar ridge and vestibular mucosa (23.4%). In the study of Sargaran et al., the most common affected sites were the alveolar ridge and vestibule, and then tongue. In the studies of Delavarian et al. (51), Jovanovic et al. (52) and Izarzagaza et al.
(53), similar to the results of the present study, tongue has been introduced as the most common affected site. Rabiei et al. introduced lips and tongue as the most common sites of developing oral cancer (54). It worth mentioning that the higher incidence of oral cancer in the tongue may be attributed to greater muscle activity of the tongue. One of the limitations of the present study is the retrospective data collected based on patients' hospital records, and thus they may not represent all cases of oral cancer in the population. Therefore, further study in this field is recommended. In future studies, it is recommended to investigate the family members of patients with oral cancer who are genetically related to these patients to survey the impacts of genetic factors on the development of the disease.
CONCLUSION
According to our study, the presence of antigen A on cells may increase the risk of oral cancer, whereas O blood type was less common in these patients. Given the higher prevalence of oral cancer in Ablood type and people over the age of 50, we can target people over the age of 50 withA blood type who are used to smoking and teach them that they are more susceptibleto oral cancer, compared to people with other blood types. We can also consider a screening schedule for this group.
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