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The present case‐control study aimed to investigate the role of interaction of glutathione‐s‐transferase (GST) genotypes with environmental risk factors in determining susceptibility to head and neck squamous cell carcinoma (HNSCC) involving 1,250 cases and equal number of healthy controls. An increase in the risk of HNSCC and its subsites (larynx, pharynx, and oral cavity) was observed among the cases with null genotypes of GSTM1 (odds ratio [OR] = 1.87) or GSTT1 (OR = 1.39) while reduced risk (OR = 0.81) was observed the cases with variant genotype of GSTP1. Tobacco use in the form of smoking or chewing interacted multiplicatively with GSTM1 or GSTT1 to increase the risk several folds (3–10 folds) in HNSCC and its subsites. Alcohol use also increased the risk (2–3 folds) to HNSCC and its subsites in cases with null or variant genotypes of GSTs, though this risk was of lesser magnitude when compared to the tobacco users. A synergistic effect of both, tobacco smoking and alcohol drinking, led to several folds (25‐folds) increased risk to HNSCC among the cases with null genotype of GSTM1 and GSTT1 when compared to nonsmokers and nondrinkers with wild genotype of GSTM1 and GSTT1 in controls. Furthermore, cases with variant genotypes of GSTP1 (Val/Val) showed superior treatment response with improved survival rate and lower risk of death when compared to the patients with wild type genotype (Ile/Ile). The data suggest that though polymorphism in GSTs may be a modest risk factor for determining HNSCC risk, gene‐environment interactions significantly modify the susceptibility to HNSCC by several folds.

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Adjuvant radiotherapy (RT) in buccal mucosa cancers is guided by histopathological factors. The decision to treat ipsilateral or bilateral draining lymph node is on physician discretion and guidelines do not have a defined indication regarding this. We aimed to analyze the failure patterns and survival in buccal mucosa cancers treated with adjuvant ipsilateral RT. Materials and Methods: One hundred sixteen cases of post-operative buccal mucosa cancers-pT3 or more, node positive, close margins (1-5 mm), lymphovascular invasion positive, perineural invasion positive, depth of invasion >4 mm-treated with RT to primary and ipsilateral nodes from May 2013 to May 2019 were retrospectively analyzed. Patients were treated to a dose of 60-66 Gy (44 Gy in the first phase and a coned down boost of 16-22 Gy in the second phase) with three-dimensional conformal radiotherapy on a linear accelerator. Primary end point was to assess control rates and secondary end point was to evaluate the overall survival (OS) and disease-free survival (DFS) outcomes. Results: Median age was 46 years with male; female ratio of 110:6. The edition of the American Joint Committee on Cancer stage distributions were I (3.4%), II (34.4%), III (24.1%), and IV (37.9%). At a median follow-up of 22 months, crude rates of local failure, regional failure, and contralateral neck failure were 9.4%, 10.3%, and 3.4%, respectively. The 2-year contralateral neck control rate was 94.9%. Pathological positive node portended poorer OS (86.6% vs. 68.6%; p = 0.015) and DFS (86.5% vs. 74.9%; p = 0.01). Conclusion: Incidence of contralateral recurrence with ipsilateral irradiation in buccal mucosa cancers is low with descent survival outcomes, particularly in node negative cases.

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