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Association of genetic variability in enzymes metabolizing chemotherapeutic agents with treatment response in head and neck cancer cases
Author(s) -
Dhawan Ankur,
Ruwali Munindra,
Pant Mohan C,
Rahman Qamar,
Parmar Devendra
Publication year - 2017
Publication title -
asia‐pacific journal of clinical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.73
H-Index - 29
eISSN - 1743-7563
pISSN - 1743-7555
DOI - 10.1111/ajco.12446
Subject(s) - head and neck cancer , head and neck , medicine , cancer , association (psychology) , chemotherapeutic drugs , oncology , cancer research , surgery , psychology , psychotherapist
Aim The prevalence of genetic variants of thiopurine S‐methyltransferse ( TPMT ) and dihydropyrimidine dehydrogenase ( DPD ) in healthy controls (500) and the treatment response in 500 cases of head and neck cancer of north Indian origin was studied. Methods Blood collected from all the subjects was used for isolation of DNA followed by genotyping studies. The cases received cisplatin and 5‐fluorouracil (5‐FU) or chemo‐radiotherapy and treatment response was measured using WHO criteria. Results Low frequency of heterozygous mutant genotypes of TPMT*2 (2%), TPMT*3B (2.2%), TPMT*3C (4.6%), DPD IVS14+1G>A (3.6%) and G1601A (3%) was observed, although no homozygous mutants could be identified. Treatment response studies in cases receiving cisplatin and 5‐FU or chemo‐radiotherapy revealed that the number of nonresponders was higher in cases who carried variant genotypes of TPMT*3B (62.50%) or TPMT*3C (59.26%) or DPD IVS14+1G>A (61.90%). Likewise, the number of nonresponders was still higher in cases carrying combination of these genetic variants. Furthermore, the frequency of nonresponders was higher in cases who carried the variant genotypes of TPMT or DPD and were also tobacco users. Conclusions Our data clearly show that TPMT and DPD genes are polymorphic in the north Indian population and may be important in determining the treatment response in cases. The data have also suggest tobacco may play an important role in determining the outcome of cancer therapy and there is an urgent need for assessment of drugs for their efficacy/toxicity in smokers compared to nonsmokers.