RESUMO
UNLABELLED: The Phosphoinositide-3-kinase catalytic alpha polypeptide (PIK3CA) is an important regulator of cell signaling pathways in human cancers. Mutations in PIK3CA were found to be associated with more aggressive clinical outcome and aberrant activation of cellular mechanisms in cancers. Hence the present study aimed to understand the mutations in the PIK3CA gene in head and neck squamous cell carcinomas (HNSCC). After the approval of the Institutional Ethics Committee we recruited 129 HNSCC patients and 150 healthy controls for screening of mutations in the helical (exon9) and kinase domain (exon 20) of the PIK3CA gene using PCR, SSCP and Sanger Sequencing. We found about 60.46% of HNSCC patients and 26% of controls with the following mutations 1634A>C (E545A) and 3075C>T (T1025T) in the helical and kinase domains of PIK3CA. Both these mutations 1634A>C and 3075C>T were more prominent in oral cancers, advanced stages of HNSCC and tobacco plus alcohol habits (p<0.05). Hence, we conclude that the distribution of mutations of PIK3CA in HNSCC were associated with demographic (tobacco and alcohol) and clinical parameters (advanced stage, primary site) of HNSCC. It is possible that when this pathway is overactive due to mutations, it may reduce apoptosis and allow proliferation of the tumor cells. Therefore we propose that these mutations may serve as prognostic biomarkers, and can also be proposed as novel therapeutic targets for HNSCC. KEYWORDS: PI3 kinase, gene polymorphism, helical domain, kinase domain, oral cancers.
RESUMO
OBJECTIVE: To define the demographic risk profile and stage at diagnosis among the head and neck cancer (HNC) patients reported in two hospital-based cancer registries in Andhra Pradesh. MATERIALS AND METHODS: A cross-sectional study was conducted in patients with histologically confirmed diagnosis of squamous cell carcinoma of the head and neck during 2002-2006. Data on the demographic profile and clinical information were obtained from hospital and clinical records. Staging was based on the American Joint Committee on Cancer and included primary tumor size (T), regional neck status (N), and group stage. The site of cancer was classified based on the International Classification of Disease for oncology (ICD-02). RESULTS: A total of 5458 cases of HNC were included in this study. Majority of the subjects were in the age range of 40-69 years with a significant male preponderance in all the age groups (P<0.001). The most common habit was the combination of smoking, alcohol, and chewing in both males and females (20.1 and 35.1%, respectively) (P<0.001). Tongue and buccal mucosa were the most common sites of cancer in both males (26.8 and 12.8%, respectively) and females (22.9 and 19.8%, respectively) (P<0.001). Tongue was the commonest site of cancer occurrence with respect to all the habits (both singly and in combination) except for chewing tobacco where buccal mucosa was the most common site. Males were more likely to be diagnosed in stage 3 (37.6%) and 4 (20.6%), while females were diagnosed in stage 1 (36.3%) and 2 (32.7%) (P<0.001). CONCLUSION: A male preponderance of cancer occurrence and combination of all the three habits (smoking, alcohol, and chewing) were found to be the significant risk factors. Males were more likely to be diagnosed later than females.
