Rajkumar, T (2011) Molecular Studies on common cancers of South India. Post-Doctoral thesis, Doctor of Science (D.Sc.), The Tamil Nadu Dr. M.G.R. Medical University, Chennai.
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Abstract
1. The author, a qualified Medical Oncologist, on his return from UK in 1994 after taking his Ph.D. in Molecular Oncology set up the first Molecular Oncology laboratory in South India. 2. The author has shown that HPV is an important causative agent in the causation of cervical cancer in Indian women. 3. His study for the first time in the country identified 12 high risk subtypes and 7 low risk subtypes in Indian women with and without cancer. 4. HPV16 and 18 were the most common subtypes seen. The study for the first time showed the prevalence of other high risk subtypes HPV33, 56, 45, 31, 51 and 52 in Indian cervical cancer patients. The study also showed a high rate of multiple infection with high risk sub-types (16.8%). Both these issues could have implications in the effectiveness of HPV vaccines in preventing cervical cancer. 5. The author has shown for the first time a high prevalence of high risk HPV infection in control women (14%). HPV16 was also the most common subtype seen in controls as well. 6. The author’s study has identified other risk factors including paan-chewing with or without tobacco (first such report), high parity (>4 live births), report of extramarital sexual activity in her husband, early menopause, age at first sexual intercourse (<15 years), age at first pregnancy (<17) and 2 or more sexual partners. High consumption of fruits and vegetables reduced the risk by nearly 50% for cervical cancer. 7. Using microarray and RQ RT-PCR techniques, the author has identified a 7 gene signature which can help predict response to radiotherapy in patients with stage IIB and IIIB cervical cancer. This will help avoid unnecessary chemotherapy and reduce the cost of treatment and the toxicity. 8. Author has shown Bcl2 protein overexpression to be a poor prognostic indicator in cervical cancers. This was later confirmed in a larger study (doctoral thesis work of Dr.Vijayalakshmi) which also identified c-myc as a strong prognostic indicator, independent of stage. 9. The author has identified several genes which have been for the first time found to be differentially expressed in invasive cervical cancer compared to varying grades of dysplasia and normal cervical tissue. These offer the potential for targeted therapy. The ability to retard the growth of cervical cancer cell lines using a dominant negative UBE2C, has shown the potential of targeted therapy for cervical cancer. This is also first such attempt in cervical cancer. 10. The author has studied MMP3 protein expression in cervical cancers, dysplasias and normal cervical tissue for the first time. Overexpression was associated with poorer response to treatment. 11. The author has found p16 protein to be overexpressed in dysplasias and in cervical cancer. This could be potentially useful as a surrogate marker for higher grade dysplasias likely to progress. 12. The author was part of the Multi-centre study which evaluated the role of HPV in oral and oro-pharyngeal cancers. This study showed a sub-set of oro-pharyngeal cancers to be associated with high risk HPV, especially HPV16. 13. The study helped identify other risk factors for oral cavity cancers, which include tobacco smoking, drinking alcohol, paanchewing with or without tobacco, poor oral hygiene, low Body Mass Index (BMI) and oral sex. High consumption of fruits and vegetables helped reduce the risk of oral cavity cancer. 14. The author established the country’s first comprehensive hereditary cancer detection and prevention program. This program does gene testing (BRCA1, BRCA2, MSH2, MLH1, RET, p53) free of cost for eligible patients. 15. The author had identified 6 novel BRCA1 mutations, all of which have been submitted to GenBank. His study has shown the BRCA1 185delAG to be the common mutation seen in the south Indian patients. However, this is not a founder mutation, as these are ethnically different individuals and from different regions and in some with no prior family history of cancer. 16. Teaming up with an International study group, the author did not find BRCA2 c.157_157insAlu mutation in any of the 91 south Indian patients tested. This mutation was confirmed to be a founder mutation specific to patients with Portuguese origin. 17. The author was the first to carry out gene expression studies on gastric cancer in our country. This helped identify 18 new genes as being differentially expressed in gastric cancer, for the first time. Using the Quantibody protein array, he has identified potential biomarkers for early diagnosis of gastric cancer. 18. The Author was the only Indian to participate in the International Collaboration of Epidemiological Studies of Cervical Cancer. This helped confirm the findings in a larger cohort of patients (>10,000) and controls (>30000). The metaanalysis confirmed parity, age at first child birth, tobacco smoking, use of combined oral contraceptives (>5 year current users) or injectable progestagens, multiple sexual partners (≥6), and early age of first sexual intercourse (≥14).
| Item Type: | Thesis (Post-Doctoral) |
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| Uncontrolled Keywords: | Molecular Studies, common cancers, South India. |
| Subjects: | Respiratory Medicine > Medical Oncology > Respiratory Medicine > Medical Oncology |
| Depositing User: | Subramani R |
| Date Deposited: | 20 Jan 2019 10:34 |
| Last Modified: | 24 Oct 2022 13:46 |
| URI: | http://repository-tnmgrmu.ac.in/id/eprint/10415 |
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