| Abstract|| |
Background: An individual's risk towards development of cancer depends not only on environmental factors or extrinsic exposure to carcinogens but also on individual's genetic susceptibility. Aim: To determine two genetically established parameters such as prevalence of GSTM1 null polymorphism and analysis of Palmar dermatoglypics (PD) in patients with Oral Leukoplakia (OL) and Controls. Materials and Methods: Group I (cases) 30 patients with established histopathological diagnosis of OL and Group II (controls) 30 patients without any habits of tobacco, alcohol usage and without OL were selected. After informed consent, the palm prints were recorded using a Canon PIXMA MP250 scanner and 2 ml of blood was collected and transported under cold cycle and taken for evaluation of GSTM1 null polymorphism using Multiplex PCR. Results: There exists a highly significant difference in GSTM1 null polymorphism (p-0.002), Finger ridge patterns (arches- p-0.027, loops p-0.001, whorls p-0.001), hypothenar pattern (p-0.015), ATD angle (p-0.001), AB count (p-0.007) between cases and controls. Similarly, when analysing the GSTM1 null polymorphism with PD among cases, there exists a significant association between loops (p-0.001), AB count (p-0.058) and hypothenar pattern (p-0.076), respectively 43% of OL cases had alteration in both which implies that those patients are at a higher risk of developing cancer. Conclusion: Not all patients who smoke or chew tobacco develop cancer. This could probably be due to the individual's genetic susceptibility. Environment gene interactions, in the form of GSTM1 polymorphism, and carcinogenesis, share links that can help in the prediction of risk for oral cancer development, and use of such markers can aid in prediction of oral cancer susceptibility in exposed individuals. Palm prints once formed do not change throughout life and are not influenced by environment. It can also serve as genetic markers to predict the risk of occurrence of oral cancer.
Keywords: GSTM1 null polymorphism, PD, tobacco
|How to cite this article:|
Yogesh L, Aswath N. GSTM1 null polymorphism and palmar dermatoglypics in oral leukoplakia. Indian J Dent Res 2021;32:69-73
|How to cite this URL:|
Yogesh L, Aswath N. GSTM1 null polymorphism and palmar dermatoglypics in oral leukoplakia. Indian J Dent Res [serial online] 2021 [cited 2021 Oct 17];32:69-73. Available from: https://www.ijdr.in/text.asp?2021/32/1/69/321366
| Introduction|| |
Carcinogenesis is a multistep process and individual's risk to the cancer development depends not only on environmental factors or extrinsic exposure to carcinogens but also on the individual's genetic susceptibility. In head and neck cancer, tobacco exposure and alcohol consumption are predominantly the most important external factors for tumour formation., In spite of the risk of tobacco exposure, the majority of patients who smoke or chew tobacco do not get oral cancer and also the vice versa. Factors influencing tobacco-exposed individuals to develop a malignancy may include a combination of both tobacco exposure and genetic susceptibility.
Individual's susceptibility to cancer may be partly explained by variability in enzymatic activities of metabolic genes. Genetic mutations related to enzyme production for tobacco products metabolism may lead to greater risk of carcinogenesis in relation to oral mucosa. The majority of tobacco carcinogens are metabolized via complex enzymatic mechanisms concerning both activation and detoxification reactions. Individual's vulnerability to cancer may be partly explained by unpredictability in enzymatic activities of phase I and phase II metabolic genes. Hence variations in the expression of these genes due to heritable genetic polymorphisms may change the course of carcinogenesis by changing the exposure levels of tobacco resultant carcinogens.
Given equal exposure to the same carcinogens, individuals will differ in their internal processing of the carcinogen depending on genetic background, acquired individually and other past or continuing exposures. Phase I enzymes [e.g. genes of cytochrome P450 (CYP) family] are commonly accountable for translation of exogenous exposures into carcinogenic metabolites. The majority of these metabolites are extremely reactive with DNA and accountable for adduct configuration and consequent DNA mutation. Excretion of these intermediate metabolites need phase II enzymes [e.g. glutathione S-transferase (GST) and N-acetyl transferase (NAT) families] to diminish the DNA-adduct formations.
GST and its polymorphism
GSTs are dimeric proteins that help in catalysing the conjugation reactions between glutathione and tobacco smoke substrates, like aromatic heterocyclic radicals and epoxides. GSTs also modulate the stimulation of further enzymes and proteins implicated in cellular functions, like DNA repair. Hence it is important for maintaining cellular genomic integrity there by playing an important role in cancer vulnerability., GST M1 products catalyse the conjugation of glutathione to epoxide derivatives of polycyclic aromatic hydrocarbons, the major carcinogens established in the tobacco smoke. Numerous polymorphisms take place in the genes encoding GSTs. Three different polymorphisms have been expressed at the GSTM1 locus on chromosome 1p13.3.5. Two loci in particular, GSTM1 (mu-type) and GSTT1 (theta-type) may be of significance for vulnerability to HNSCC. The GSTM1 gene exhibits a deletion polymorphism, particularly in case of homozygosity (GSTM1 null) may lead to the complete absence of phenotypic enzyme activity. The GSTM1 (null) genotype has been established to be considerably linked with an increased risk of oral squamous cell carcinoma (OSCC).,, As a result, variations in the expression of these genes due to heritable genetic polymorphisms modulate carcinogenesis by varying the exposure levels of tobacco derived carcinogens.
Dermatoglyphics is the systematic study of fingerprints from palms, fingers, soles and toes of human beings and animals. These ridges are epidermal in origin and they develop on the volar surfaces around 6th weeks of gestation and attain maximum size around 12th to 13th weeks. This means that the genetic message contained in the genome normal or abnormal is deciphered during this period and is also reflected by dermatoglyphics. Dermatoglyphic patterns remain unchanged during life and may occasionally play an important role in analysis of numerous disorders with genetic background. Various studies have revealed relationship between dermatoglyphics and different forms of cancer. Dermatoglyphics may be of immense clinical implication to isolate those individuals who are at a greater risk for developing these diseases.
To determine two genetically established parameters such as prevalence of GSTM1 null polymorphism and analysis of Palmar dermatoglypics (PD) in patients with Oral Leukoplakia (OL) and Controls.
| Materials and Methods|| |
A case control study was done among the outpatients visiting the Department of Oral Medicine and Radiology. Patients willing to participate in the study were included after obtaining informed consent. Institutional ethical clearance was also obtained. Out of the total 60 patients included, group I (30 patients) were the cases with established histopathological diagnosis of Oral Leukoplakia (OL) and Group II (30 patients) were controls who did not have the habit of using neither tobacco, nor alcohol and without OL. For Group I all cases clinically diagnosed and histopathologically confirmed as OL associated with the use of tobacco were included. The exclusion criteria for Group I were other white lesions such as lichen planus, frictional keratosis, white spongy nevus, oral submucous fibrosis, linea alba etc., and patients with systemic disorders such as diabetes, hypertension, congenital cardiac diseases, myocardial infarction, bronchial asthma, pulmonary tuberculosis, schizophrenia, bile ducts atresia etc., which might lead to an overlap of the dermatoglyphic pattern and hand injuries. Normal healthy patients without any habits of usage of tobacco and alcohol and individuals without OL were included as controls (Group II). Exclusion Criteria for Group II included patients with systemic disorders which might alter the dermatoglyphic pattern and Hand injuries.
After obtaining informed Consent the following procedures were done. (1) The palm prints were recorded using Canon PIXMA MP250 scanner [Figure 1]. They were evaluated qualitatively for the presence of arches, loops and whorls [Figure 2] Hypothenar pattern [Figure 3] and quantitatively for AB Count [Figure 4] ATD angle [Figure 5]. (2) Two millilitres of blood was collected, transported under cold cycle and taken for evaluation of GSTM1 null polymorphism using Multiplex Polymerase Chain Reaction. Analysis of PD were done based on previous study done by the author. Evaluation of GSTM 1 null polymorphism using Multiplex PCR was done based on the method described by Gronau et al. [Figure 6]. The values of PD analysis and Gene analysis were entered in the formulated excel sheet and the results were statistically analysed.
|Figure 1: Fingerprint recorded using Canon MPC scanner and the scanned image|
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|Figure 6: Gel electrophoresis image showing the presence of glutathione S transferace M1 (GSTM1) gene in the wells (white color) and the in between blank spaces in the lane indicate the absence of the gene|
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| Results|| |
The results of qualitative and quantitative analysis were presented in the [Table 1], [Table 2], [Table 3]. The results were further analysed by comparing the PD and GSTM1null polymorphism among cases to ascertain the genetic susceptibility of individuals with OL in developing oral cancer [Table 4]. The mean values for individual PD variables among cases were calculated (arches –2, loop -5, whorls -3, ATD angle -38, AB count -39) and compared with GSTM1 null polymorphism. Arches <2 and >2, loops >5 and <5, whorls >3 and <3, ATD angle <38 and >38, AB count <39 and > 39 were compared. Statistical analysis by Fisher's exact test reveals significant association between loops (P value-0.001), AB count (p value-0.058), and hypothenar pattern (p value-0.076) with GSTM1 null polymorphism among cases.
|Table 1: Finger ridge patterns among the study groups – Independent t test|
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|Table 2: Showing the mean ATD angle, AB count among the study groups – Independent t test|
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|Table 4: Cumulative analysis of GSTM1 null polymorphism with palmar dermatoglyphics among cases (Fischer's Exact Test)|
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| Discussion|| |
Oral cancer, being the most common cancer in India is caused by etiological factors like tobacco, alcohol, virus, dietary, and genetic factors. Genetic susceptibility to external carcinogen may be important in the occurrence of squamous cell carcinoma, as many persons though exposed to tobacco and alcohol do not develop oral cancer and vice versa. Hence, identifying individuals at high risk for OL will be of great value to reduce the occurrence of the future risk of oral cancer.
The glutathione-s-transferases (GSTs) are a family of enzymes known to play significant roles in the detoxification of several carcinogens found in tobacco. GST also modulate DNA repair. This group of enzymes is therefore important for maintaining cellular genomic integrity and, hence, may play an important role in cancer susceptibility. GSTM1null polymorphisms are characterized by the complete loss of enzyme. The GSTM1 null polymorphism was demonstrated to be a risk factor for developing OL in betel quid/tobacco chewers in study based on ethnic Indian population. Various studies suggest an association between the GSTM1 null genotype with oral cavity or head and neck cancer., Various palmar dermatoglyphics and GSTM1 null polymorphism studies have already established significant association with OL individually., Since both PD and GSTM1 gene are genetically associated, an attempt has been made to correlate the two though the gene that determines both the parameters are different.
Palmar dermatoplyhics is an easy and inexpensive modality. In our study, there was predominance of loops and whorls, decrease in arches, ATD angle, AB ridge count, and presence of hypothenar pattern among cases than in controls. In a similar study done by Venkatesh Naik Masoor et al. there was predominance of arches and loops, decrease in whorls, AB ridge count, and presence of hypothenar pattern among cases than in controls.GSTMI null polymorphism was noticed among 67% of cases. When correlation of palmar dermatoglyphics with GSTM1 null polymorphism was done 43% of OL cases had alteration in which both implies that those patients are at a higher risk of developing cancer.
| Conclusion|| |
Not all patients who smoke or chew tobacco develop cancer. This could probably be due to the individual's genetic susceptibility. Environment gene interactions, in form of GSTM1 polymorphism and carcinogenesis, share links that can help in the prediction of risk for oral cancer development, and use of such markers can aid in prediction of oral cancer susceptibility in exposed individuals. Palm prints once formed do not change throughout life and is not influenced by environment. It can also serve as genetic markers to predict the risk of occurrence of oral cancer.
The small number of subjects was a major limitation. The null polymorphism was studied in the expression of GSTM1 gene alone, while several genes perform same function which implies the need to study several genetic polymorphisms to identify individual's risk. Further longitudinal studies need to be undertaken.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Sciubba JJ. Oral cancer and its detection. History taking and the diagnostic phase of management. J Am Dent Assoc 2001;132:12-8.
Van der Waal I, Axéll T. Oral leukoplakia: A proposal for uniform reporting. Oral Oncol 2002;38:521-6.
Gronau M, Koenig-Greger D, Jerg M, Riechelmann H. Gene polymorphisms in detoxification enzymes as susceptibility factor for head and neck cancer. Otolaryngol Head Neck Surg 2003;128:674-80.
Drummond SN, De Marco L, Noronha JC, Gomez RS. GSTM1polymorphism and oral squamous cell carcinoma. Oral Oncol 2004;40:52-5.
Duarte EC, Silva MS, Gomez MV, Gomez RS. GSTM1 polymorphism and oral leukoplakia. J Oral Pathol Med 2006;35:202-5.
Matthias C, Bockmühl U, Jahnke V, Jones PW, Hayes JD, Alldersea J, et al
. Polymorphism in cytochrome P450 CYP2D6, CYP1A1, CYP2E1 and glutathione S-transferase, GSTM1, GSTM3, GSTT1 and susceptibility to tobacco-related cancers: Studies in upper aerodigestive tract cancers. Pharmacogenetics 1998;8:91-100.
Fryer AA, Strange RC. The glutathione S-transferases: Influence of polymorphism on cancer susceptibility. IARC Sci Publ 1999;148:23149.
Chern HD, Chiang CP, Chien YC, Chuang J, Hung HC, Kuo YS, et al
. Genetic polymorphisms of CYP2E1, GSTM1, and GSTT1; environmental factors and risk of oral cancer. Cancer Epidemiol Biomarkers Prev 1997;6:901-5.
Hahn M. Genetic polymorphisms of drug metabolizing enzymes and susceptibility to oral cavity cancer. Oral Oncol 2002;38:486-90.
Sinha CK, Meel M, Bayan B. Using dermatoglyphics pattern to identify the left handed unique pattern and its biological significance-if any. World Appl Sci J 2012;20:11071113.
Weizman Z, Vardi O, Binsztok M. Dermatoglyphic (fingerprint) patterns in celiac disease. J Pediatr Gastroenterol Nutr 1990;10:451-3.
Lakshanika, Aswath N. A new innovative technique for analysis of palmar dermatoglyphics in oral leukoplakia patients. Res J Pharm Biol Chem Sci 2016;7:1940-8.
Atasu M. Dermatoglyphic findings in dental caries: A preliminary report. J Clin Pediatr Dent 1998;22:147-9.
Palot H. Dermatoglyphics findings in oral cancer. Balkan J Stomatol 2004;8:105-8.
Agarwal R, Chowdhary DS, Agarwal N, Rajnee, Dhamdra JS. Digital dermatoglyphics in head and neck cancer. J Postgrad Med Inst 2011;25:101-5.
Vijayaraghavan A, Aswath N. Qualitative andquantitative analysis of palmar dermatoglyphics among smokeless tobacco users. Indian J Dent Res 2015;26:483-7.
] [Full text]
Venkatesh E, Bagewadi A, Keluskar V. Palmar dermatoglyphics in oral leukoplakia and OSCC patients. J Indian Acad Oral Med Radiol 2008;3:94-9.
Dr. Nalini Aswath
Department of Oral Medicine and Radiology, Sree Balaji Dental College and Hospital, Chennai - 100, Tamil Nadu
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
[Table 1], [Table 2], [Table 3], [Table 4]