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Genetic Polymorphism of CYP1A1 and GSTM1 Amongst Indian Tobacco Consumers with Risk Evaluation of Oral Cancer and Precancer Development

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Abstract

Xenobiotic metabolic enzymes CYP1A1 and GSTM1 are known to increase the risk of head and neck cancer. However, their role in the development of oral potentially malignant disorders (OPMDs) in the Indian population is uncertain. This study aimed to investigate the CYP1A1 and GSTM1 gene polymorphism in the urban population of the state of Delhi as well as to investigate the risk of disease progression. Genotype analysis via polymerase chain reaction was conducted in 1169 cases and 1046 controls with regard to GSTM1 and CYP1A1 (ile-val) genes. The oral lesions were biopsied for histopathological diagnosis. Follow-up of the subjects was done at 6-month intervals and the status of the lesions was recorded as static, progressed, or regressed. Descriptive analysis was done with a p-value ≤ 0.05 and odds ratio with a 95% confidence interval being considered for a measure of association. Subjects who consumed both tobacco and alcohol and developed OPMD lesions were 8.2 times more likely to harbour CYP1A1 Val/Val genotype (p = 0.047; OR = 8.224; 95% CI = 1.024–66.037). The highest progression rate and lowest regression rate were found for the CYP1A1 Val/Val genotype in our sample. The CYP1A1 Val/Val genotype may be associated with an increased risk of development of OPMDs amongst consumers of both tobacco and alcohol. Real-time activity-based sensing of isoforms of the CYP1A1 enzyme in living systems is needed to validate the same.

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Acknowledgements

We thank the field workers for their assistance with the administration of this study.

Funding

The study was supported by the ICMR Task Force Project: Project ID: 5/13/3/TF/2001/NCD-III.

Author information

Author notes

  1. Jatinder Kaur and Anubhuti Sood are equally contributing first authors.

Authors and Affiliations

  1. MolQ Laboratory, Molecular Quest Healthcare Pvt. Ltd, Gurgaon, Haryana, India

    Jatinder Kaur

  2. Department of Oral Pathology and Microbiology, Centre for Dental Education and Research, All India Institute of Medical Sciences, Delhi, India

    Anubhuti Sood

  3. Department of Biochemistry. AIIMS New Delhi, Delhi, India

    Ranju Ralhan

  4. Mount Sinai Hospital, Toronto, Canada

    Ranju Ralhan

  5. AIIMS New Delhi, Delhi, India

    Kamala Lakshmi

  6. Department of Otolaryngology, AIIMS, Delhi, India

    Sudhir Bahadur

  7. Centre for Community Medicine, AIIMS, Delhi, India

    Shashi Kant

  8. Department of Pathology, AIIMS, Delhi, India

    S. Datta Gupta

  9. Department of Biostatistics, AIIMS New Delhi, Delhi, India

    R. M. Pandey

  10. Department of Radiotherapy, IRCH, AIIMS, Delhi, India

    P. K. Julka

  11. Centre for Dental Education & Research (CDER), Department of Public Health Dentistry), AIIMS, New Delhi (Delhi), India

    Priyanka R

  12. BRA Institute Rotary Cancer Hospital, National Cancer Institute, New Delhi (Delhi), India

    G. K. Rath

  13. ICMR-NICPR, Noida, India

    Ravi Mehrotra

  14. ICMR-India Cancer Research Consortium (Chief Executive Officer), New Delhi (Delhi), India

    Ravi Mehrotra

  15. Department of Surgical Disciplines, All India, Institute of Medical Sciences (AIIMS), New Delhi (Delhi), India

    Deepika Mishra & Anurag Srivastava

Authors
  1. Jatinder Kaur
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Contributions

Contributions to the conception or design of the work, or the acquisition, analysis, or interpretation of data: AS, JK, RR, KL, RM, AnS, PR. Drafting the work or revising it critically for important intellectual content: AnS, PR, DM, AS, RM. Final approval of the version published—AS, RR, KL, AnS, PR, GKR, RMP, DM, RM, SB, SK, SDG. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved: AS, RR, KL, AnS, PR, SB, SK, SDG, GKR, RMP, DM, RM.

Corresponding author

Correspondence to Deepika Mishra.

Ethics declarations

Ethics Approval

This study was performed in line with the principles of the Declaration of Helsinki. This study was approved by the ethics committee at the Indian Council of Medical Research, New Delhi (India) (Project ID: 5/13/3/TF/2001/NCD-III).

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Informed consent was obtained from all the participants who agreed to participate in the study.

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Not required.

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The authors declare no competing interests.

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Appendix. Treatment strategies for OPMD cases

Appendix. Treatment strategies for OPMD cases

  1. I.

    Biopsy confired lesions:

    1. a)

      Leukoplakia/erythroplakia:

      • Incisional biopsy (size > 4 × 4 cm) of the large diffuse lesion.

    2. b)

      Oral submucous fibrosis (OSF):

      • Wedge biopsy from the area of OSF

      • Any ulcerated area or growth biopsied.

      • Trismus relieved by division of fibrous bands at palato-glossal arch and pterygomandibular raphe to achieve an inter-incisor distance of 3–4 cm.

      • Symptomatic treatment with infra-red and ultra-violet rays

      • Trismus screw and muscle relaxation exercises.

      • Multi-vitamin tablets with fibrinolysin combinations.

    3. c)

      Lichen planus and melanoplakia:

      • Treatment same as leukoplakia

      • Multi-vitamin tablets, balanced diet.

      • Counseling, yoga, and meditation for stress.

  2. II.

    Other Lesions:

    • Symptomatic treatment

    • Referral to concerned department (ENT, Oral Medicine, Dermatology) for appropriate treatment.

  3. III.

    Health Education:

    • Emphasis on the awareness of the harmful effects of tobacco use.

    • Importance of self-examination in detecting oral cancer.

    • To quit tobacco use.

    • Pamphlets containing relevant health education material about dental health and harmful effects of tobacco use distributed to the study subjects (copy of pamphlet enclosed).

  4. IV.

    Dental interventions:

    • Grinding of sharp cusps

    • Scaling and polishing

    • Extraction of grossly decayed teeth/root stumps/root canal treatment of teeth that can be saved.

    • Replacement of faulty dentures with well-fitting removable partial denture /fixed partial denture.

    • Replacement of denture material /filling materials if found to be allergic.

    Numbers I, II, and III in the mobile van. The rest of the cases seen in the Dental/Surgery/ENT OPD and Head and Neck Clinic at AIIMS.

Oral Cancer

  • Early small malignant lesions (less than 2 cm in diameter) a choice of radiotherapy or surgery.

Follow up regularly at 6-month intervals.

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Kaur, J., Sood, A., Ralhan, R. et al. Genetic Polymorphism of CYP1A1 and GSTM1 Amongst Indian Tobacco Consumers with Risk Evaluation of Oral Cancer and Precancer Development. Indian J Surg 85, 1130–1138 (2023). https://doi.org/10.1007/s12262-023-03670-x

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