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ORIGINAL ARTICLE
Year : 2016  |  Volume : 12  |  Issue : 1  |  Page : 126-130

Is there an association between oral submucous fibrosis and ABO blood grouping?


1 Department of Public Health Dentistry, People's College of Dental Sciences and Research Centre, Bhopal, Madhya Pradesh, India
2 Department of Periodontics, RKDF Dental College, Bhopal, Madhya Pradesh, India
3 Department of Public Health Dentistry, People's Dental Academy, Bhopal, Madhya Pradesh, India
4 Department of Oral Medicine and Radiology, Governament Dental College, Shimla, Himachal Pradesh, India
5 Department of Physiotherapy, Southern Institute of Medical Sciences College of Physiotherapy, Guntur, Andhra Pradesh, India
6 Department of English, People's College of Research and Technology, Bhopal, Madhya Pradesh, India

Date of Web Publication13-Apr-2016

Correspondence Address:
Venu K Gopal Reddy
Department of Public Health Dentistry, People's College of Dental Sciences and Research Centre, Bhopal - 462 037, Madhya Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.151857

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 > Abstract 

Background: Oral submucous fibrosis (OSMF) is one of the most common premalignant conditions in Indian subcontinent due to the traditional use of Areca nut and its various preparations. The genetic predisposition has also been reported in its etiopathogenesis. The rate of malignant transformation is between 7% to 14%.
Aim: To evaluate whether ABO blood group is related to OSMF risk.
Subjects and Methods: It was a cross-sectional hospital-based study. A convenient sample of 164 study subjects constituted the cases and 180 subjects constituted the comparison group.
Statistical Analysis Used: The results were analyzed using chi-square test and odds ratio.
Results: The chi-square analysis could not establish any significant relationship between OSMF and ABO blood group. But, when the strength of the association was measured using odds ratio, subjects with blood group A had 1.181 times higher risk of developing OSMF in comparison to other groups.
Conclusion: The subjects with blood group A were at higher risk of developing OSMF in comparison to others. By performing blood group determination using a routine method at outreach programs, the susceptible individuals can be identified and counselled to quit the habit, thereby avoiding potential complications.

Keywords: ABO blood group, areca nut, odds ratio, oral submucous fibrosis, premalignant condition


How to cite this article:
Gopal Reddy VK, Moon NJ, Sharva V, Guruprasad, Reddy EK, Chandralkala S. Is there an association between oral submucous fibrosis and ABO blood grouping?. J Can Res Ther 2016;12:126-30

How to cite this URL:
Gopal Reddy VK, Moon NJ, Sharva V, Guruprasad, Reddy EK, Chandralkala S. Is there an association between oral submucous fibrosis and ABO blood grouping?. J Can Res Ther [serial online] 2016 [cited 2019 Dec 10];12:126-30. Available from: http://www.cancerjournal.net/text.asp?2016/12/1/126/151857




 > Introduction Top


Cancer is now one of the five main causes of death, in all societies. It is not only responsible for significant mortality but also causes physical, mental, financial, and sociological mutilation to an individual. According to a World Health Organization (WHO) report, in India out of ten cases of cancer, four are oral cancers and it is the 6th most common cause of death.[1] Over 90% of oral cancer lesions are oral squamous cell carcinomas (OSCC).[2] It represents the 3rd most common form of malignancy in the developing countries while it is the 8th most common in developed countries.[3] Ferlay et al., in 2013 reported a 5-year oral cancer prevalence of 6.6% among Indians and mortality due to the same as 7.6% annually.[4] A report of Indian Council of Medical Research (ICMR) in 2013 has revealed that the age-adjusted rate of oral cancer among males is as high as 17.1 per 1,00,000 population and among females is as high as 7.6 per 1,00,000 population.[5] Deepa et al., in 2012 reported an oral cancer incidence of 12.6 per 1,00,000 population.[6] Majority of OSCCs are preceded by pre-existing potentially malignant disorders like leukoplakia and oral submucous fibrosis (OSMF). This concept of a two-step process of cancer development in the oral mucosa, i. e., the initial presence of a precursor (premalignant, precancerous) lesion subsequently developing into cancer is well-established.[7]

OSMF was first described by Sushrutha (2500–3000 BC) as Vidhari, who had recognized it as a mouth and throat melady.[8] OSMF is an insidious, chronic disease affecting any part of the oral cavity and sometimes the pharynx. Although occasionally preceded and/or associated with vesicle formation, it is always associated with juxta epithelial inflammatory reaction, followed by fibro elastic change of lamina propria, with epithelial atrophy leading to stiffness of the oral mucosa causing trismus and inability to eat.[9] The global scenario reveals that it is predominantly reported in people of South Asian region or South Asian immigrants to other parts of the world as a result of the traditional use of Areca nut and its various preparations endemic to these areas.[10] Currently, 5 million people are suffering from this precancerous condition in Indian subcontinent.[11] The worst affected are the youth between the age group of 20–40 years.[8] The estimated prevalence of OSMF in India is in the range of 0.03–3.2%.[12] There is convincing epidemiological evidence implicating Areca-nut chewing either directly or indirectly as the main etiological factor in the pathogenesis of OSMF. The genetic predisposition has also been implicated in the etiopathogenesis of OSMF.[13] The rate of malignant transformation of this premalignant condition is anywhere between 7–14%.[14] The precancerous nature of OSMF was first reported by paymaster who found occurrence of OSCC in one-third of his patients.[6]

The existence of blood groups in humans dates back to 20th century when Karl Landsteiner in 1901 described the existence of serologic differences between individuals, segregating people into one of the four groups depending upon whether their red cells contained agglutinogen “A,” agglutinogen “B,” neither A nor B (O) or both A and B (AB).[15] This invention later led to a number of serological, immunological, and genetical studies to investigate and to establish the relative susceptibility of some blood group phenotypes to certain diseases. The possibilities of the association between ABO blood group and malignancies were explored for the first time by Alexander in 1921. The study reports of Arid et al., in 1953 and Walter in 1956 revealed that blood group A was associated with increased risk of stomach cancer.[16] It was also reported that there is an existence of association between blood group antigens particularly in blood group A and oral pathologies.[17] Jaleel et al., in 2012 reported that people with blood group A had 1.46 times higher risk of developing oral cancer in comparison to other groups.[15] Mortazavi et al., in 2014 reported that patients with blood group B were 3.5 times at risk of developing oral cancer than others.[18] Akhtar et al., in 2011reported a high incidence of oral cancers in blood group B.[19] Thus, opening new arenas in oral disease research.

The blood group play an important role in immunogenetics as it is an easily accessible factor in patient's genetic make-up. Till date, there are a plethora of studies reporting the association between blood group antigens and various diseases. Surprisingly, no data has been reported relating blood group phenotypes with the OSMF. Hence, the present research was undertaken to evaluate whether ABO blood group is related to OSMF risk. If any such association exists, individuals who are known Areca-nut chewers and with susceptible blood group antigen will be counselled to quit the habit, thereby intervening the exposure to the disease at the earliest and avoiding complications.


 > Subjects and Methods Top


The present cross-sectional study was conducted in the department of Oral Medicine and Radiology of a private dental institution in Bhopal city. Ethical clearance was obtained from institutional ethical committee after obtaining the approval from research approval committee. The examiner was trained and calibrated in the department of oral medicine and radiology in diagnosing the patients of OSMF by examining 20 patients using predetermined diagnostic criteria proposed by C. B. More [20] prior to pilot study. The Kappa value obtained was 0.86. It was followed by a pilot study in order to calculate the sample size. The sample size was calculated by using the following formula:

n = z 2 pq/d 2 where,

n = desired sample size

z = standard variate, i. e., 1.96 at 95% confidence level

p = estimated prevalence, i. e., 12%

q = alternate proportion (1-p), i. e., 0.88

d = precision or acceptable error, i. e., 5%.

A total of 164 patients with OSMF constituted the final sample size. A comparable sample of 180 individuals, who were free from OSMF, constituted the comparison group. Patients with known blood dyscrasias were excluded from the study. A standard proforma was used to record the demographic details and clinical findings of each subject. The OSMF was diagnosed using the predetermined diagnostic criteria.[20] An informed written consent was obtained from the subjects, i. e., from both cases and comparison group before subjecting them to hematological investigation for blood group determination. The blood group determination was done using rapid slide method. This method was based on the principle of presence or absence of blood group specific substances like A, B, and O in the red blood cells (RBCs). The phenomenon of agglutination (Clumping) due to the interaction between aglutinogens (antigens) present on the RBC membrane and agglutinins (antibodies) present in the plasma forms the basis for this procedure. A finger prick was done with a disposable lancet. Then, clean glass slides were taken and one drop each of antiserum-A and antiserum-B was placed on the slides with the help of a dropper. The blood drop was placed on each of the antiserum on the slide. The two were mixed with the help of separate applicator sticks. After waiting for 10 minutes, the slide was gently rocked back and forth and examined for the presence of agglutination. If there was no agglutination, the RBCs were remained separated and evenly distributed. If agglutination occurred, the RBCs were merged together in clumps and lost their outline. The individual subjects with different blood groups were segregated accordingly. The data obtained was subjected to statistical analysis. The association between various blood groups antigens and OSMF was analyzed using Chi-square test and odds ratio. P < 0.05 was considered statistically significant.


 > Results Top


[Table 1] shows the distribution of ABO blood groups among cases and comparison group. Out of 164 OSMF patients, 20.1% had blood group A, 34.1% had B, 6.7% had AB, and 39.0% had blood group O. Among 180 subjects constituting the comparison group, 23.3% had blood group A, 31.7% had B, 6.7% had AB, and 38.3% had blood group O. When a comparison was made between blood groups and study subjects (case and comparison group), the Chi-square analysis could not establish any significant relationship.
Table 1: Distribution of blood group antigens among cases and comparison group

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[Table 2] reveals the strength of association between ABO blood groups and OSMF when assessed by odds ratio. It was found that people with blood group A had 1.181 times higher risk of developing OSMF compared to people with other blood groups. The relative risk for subjects with blood group AB was 1.012, followed by subjects with blood group O with a relative risk of 0.971 and blood group B having a relative risk of 0.944 (P > 0.05).
Table 2: Odds ratio showing the strength of association between ABO blood groups and oral submucous fibrosis

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The distribution of ABO blood groups among cases and comparison group according to gender shows that out of 138 male OSMF cases, 20.2% had blood group A, 30.4% had B, 6.5% had AB, and 42.0% had blood group O, whereas in the comparison group, there were 23.4%, 27.5%, 6.2%, and 40.6% people with the four blood groups, respectively. Among 26 female cases with OSMF, 19.2% had blood group A, 53.8% had B, 7.6% had AB, and 23.0% had O, while in the comparison group, 22.8%, 48.5%, 8.5%, and 28.5% had the four blood groups, respectively.

Majority of the OSMF cases (75%) were found in the age-group of 20–40 years, irrespective of the blood group they had. Very few cases were seen in the other age-groups.

When the different types of habits were compared, majority of the OSMF cases (i. e., 99% patients) had the habit of chewing Areca nut and its various preparations. The remaining 1% of the study subjects had given the history of consumption of spicy food.


 > Discussion Top


The idea of exploring the association between human genetic make-up and disease pathology is challenging. Understanding the relationship between human genetics and disease is the current field of the interest for the researchers. The human genetics is emerging as a basic biological science for understanding an individual's state of health and disease.

The attempts to establish a scientific association between ABO blood group systems and various diseases dates back to 20th century following the discovery of ABO blood group antigens by Karl Landsteiner. The ABO blood group is genetically determined and therefore is not a modifiable risk factor as are cigarette smoking, body mass index, diet, or other lifestyle-related variables.[21] The first association between the ABO blood group and disease risk was reported in English patients with stomach cancer where blood group A was associated with increased risk of stomach cancer. It was a study report of 1930s which revealed that blood group A was associated with oral pathologies that opened new insights into oral disease research. It was reported that blood group O is caries immune. Denture wearers of blood group O were more susceptible to denture stomatitis. Maxillofacial deformities were least in blood group A individuals and greater with blood group B indicating the role of ABO blood groups in various oral pathologies.[17]

In the present study, an attempt was made to explore whether ABO blood group is related to OSMF risk in order to avoid potential complications resulting from this premalignant condition in susceptible individuals as it was established that malignant transformation potential of this condition stands anywhere between 7–14%. Although, chewing Areca nut was established as the most common etiological factors in OSMF, some researchers have reported the role of genetic factors.[15] A study by Tu. HF et al., reported that 5A genotype of matrix metalloproteinase (MMP3) promoter acts as a risk factor for OSMF among male areca users.[22]

The present study demonstrates that ABO blood group is not significantly associated with OSMF. However, when the strength of the association was measured using odds ratio, it was found that blood group A is at higher odds of developing OSMF compared to other blood groups, although majority of the Indian population belong to blood group B. Our finding is in agreement with a study report of Vaish et al., in 1979 who found that blood group A is highly susceptible to OSMF and oral lichenplanus (OLP), followed by O, AB, and B in logical sequence in their proportion in descending order.[23] It is well-known that OSMF is a premalignant condition and has the potential to transform itself into oral cancers whose genetic association with blood group antigens is well-established. A study report of Tyagi et al., in 1965 revealed a non-significant association of various blood groups in patients with oral cancer. However, preponderance of blood groups A and AB was observed in their study population.[24] Another study by Mittal VP found increased incidence of oral cancer in blood group A followed by O.[25] A study report of Jaleel et al., reveled that blood group A is at a greater risk to develop oral cancer in comparison to other blood groups.[16] In contrary, a study by Ghoii et al., found preponderance of blood group B in oral cancer patients.[26] On the basis of present study, the statement of Bakare et al., proves to be true who said that the variants of ABO blood group might play an important role in immunology and in disease prevention.[27]

Areca-nut chewing is proposed as the main etiological factor in the development of OSMF. The role of other facors like vitamin deficiencies and spicy foods is almost negligible. In the present study, even though the patients of all the blood groups had the habit of chewing Areca nut, patients belonging to blood group A are having higher odds of developing OSMF.

The gender-wise distribution of the disease reveals that the male to female ratio is 5.3:1, thus showing a greater predilection for males. This could be probably because in India more number of males are indulged in to the habit of chewing arecanut and its various preparations when compared with females. Our finding is in agreement with that of Hazarey et al., in India who reported a male to female ratio of 4.9:1 among OSMF patients.[28] Thus, there appears to be a definite gender predilection for OSMF. Despite of conducting a good research on one of the most common premalignant conditions, the limitation in our study is found to be that it was a hospital-based study and the conclusions derived cannot be generalized. Further studies should be conducted at the community level so as to achieve more definite conclusions.


 > Conclusion Top


This study reports that ABO blood group is not significantly associated with OSMF. But, the subjects with blood group A have 1.18 times higher risk of developing OSMF compared to other blood groups. Blood groups are easily accessible factor (s) of human genetic make-up. By simple blood group determination, i. e., by slide method, during community outreach programs, the individuals with blood group A can be identified and can be counselled to quit the habit, thereby avoiding potential complications.

 
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