ASSOCIATION OF CLPTM1L/TERT GENE POLYMORPHISM, SMOKING, AND RISK OF NASOPHARYNGEAL CARCINOMA AMONG MALE IN YOGYAKARTA

C MEGAWIMANTI S, Jajah Fachiroh, S.P., M.Si.,Ph.D ; Dewi Kartikawati Paramita, S.Si., M.Si., Ph.D

2018 | Skripsi | S1 PENDIDIKAN DOKTER

Latar belakang: Kanker Nasofarings (KNF) merupakan kanker yang paling sering muncul di area kepala dan leher. Kejadian kanker nasofarings dipengaruhi oleh beberapa factor diantaranya paparan lingkungan seperti kebiasaan merokok dan variasi genetik seperti polimorfisme. Polimorfisme pada gen CLPTM1L/TERT rs31489 mempengaruhi koding dari protein transmembran yang dapat menyebabkan apoptosis pada cell yang sensistif untuk cisplatin dan kanker paru yang disebabkan oleh substansi genotoksik seperti rokok. Tujuan: Megetahui hubungan antara polimorfisme gen CLPTM1L/TERT rs31489, kebiasaan merokok dan kanker Nasofaring pada laki laki di Yogyakarta Metode: Penelitian ini menggunakan desain kasus control tersarang yang berbasis rumah sakit. Seratus dua puluh sampel kasus dan 120 control diperoleh dari data sekunder yang diambil dari Rumah Sakit dr.Sardjito, dan DNA yang digunakan diisolasi dari buffycoat darah tepi. Variasi genetic rs31489 yang terletak pada gen CLPTM1L/TERT dapat dideteksi menggunakan ARMS-PCR (Amplification Refractory Mutation System - Polymerase Chain Reaction). Hubungan antara kebiasaan merokok, polimorfisme gen CLPTM1L/TERT dianalisis menggunakan regresi logistic analisis dengan penyesuaian menggunakan faktor demografi sebagai faktor perancu. Hasil: Karakteristik dasar untuk kategori umur (p=0,606) dan suku (p=0,776) dari kelompok kasus dan control tidak berbeda, kecuali pendidikan (p=0,001).Sebagian besar sampel berada di stadium IV (71,4%) dan WHO tipe III (94,2%). Populasi yang memiliki genotype CA (OR = 0,61; 95% CI= 0,353 - 1,061) dan genotipe AA (OR = 0,91; 95% CI = 0,374 - 2,207) memiliki efek yang protektif pada kejadian kanker Nasofarings jika dibandingkan dengan genotype CC (wild type). Merokok meningkatkan risiko terhadap KNF dibanding populasi yang tidak merokok (OR = 1,48; 95% CI = 0,853 -2,571). Pada populasi yang memiliki genotype CA dan tidak merokok risiko kejadian KNF sedikit lebih tinggi (OR= 0,64; 95% CI = 0,328-1,256) dibandingkan populasi yang merokok (OR=0,5; 95% CI =0,185 - 1,354). Pada populasi yang memiliki genotype AA dan tidak merokok, risiko KNF meningkat 1,703 kali ( 95% CI = 0,572 - 5,068) dibanding dengan perokok yang memiki efek potektif (OR =0,2; CI =0,034 - 1,174). Kesimpulan: Genotipe CA dan AA pada gen CLPTM1L/TERT rs31489 menunjukan efek protektif pada KNF pada laki laki di Yogyakarta. Merokok meningkatkan risiko KNF pada laki laki di Yogyakarta. Merokok menunjukkan efek protektif terhadap KNF pada laki laki di Yogyakarta yang memiliki genotipe CA dan AA pada gen CLPTM1L/TERT rs31489. Genotipe AA pada gen CLPTM1L/TERT rs31489 meningkatkan risiko KNF pada laki laki di Yogyakarta Kata kunci: kanker nasofarings, polimorfisme gen CLPTM1L/TERT dan kebiasaan merokok, ARMS-PCR.

Background: Nasopharyngeal Carcinoma (NPC) consider as most common malignancy in head and neck region. The incidence of nasopharyngeal carcinoma is influenced by several factors including environmental exposure such as smoking habit and genetic factors such as polymorphism. CLPTM1L/TERT rs31489 gene polymorphism affects transmembrane protein expression which induces apoptotic in cisplatin sensitive cells and lung cancer under genotoxic substance such as tobacco smoking. Objectives: To understand the association between CLPTM1L/TERT gene polymorphism rs31489, smoking habit and the risk of nasopharyngeal carcinoma among male in Yogyakarta. Method: This study used nested hospital-based case control study design. Secondary data was included 120 samples of case and 120 control were recruited from dr. Sardjito Hospital, and the DNA samples was isolated from the buffycoat of peripheral blood samples. Genetic variation of rs31489 that located in CLPTM1L/TERT gene was determined using ARMS-PCR (Amplification Refractory Mutation System - Polymerase Chain Reaction). The association between smoking habit, rs31489 polymorphism and Nasopharyngeal Carcinoma was analyzed using logistic regression analysis, using demographic factors as confounding factors. Result: The baseline characteristic of the case and control were not different in the basis of age (p= 0.606) and tribes (p=0.776), but education (p=0.001). Most of the samples was in stage IV (71.7%) and WHO type III (94.2%). Population who had CA genotype (OR = 0.61; 95%CI= 0.353 - 1.061) and AA genotype (OR = 0.91; 95%CI = 0.374 - 2.207) had protective effect to NPC compared to CC genotype (wildtype). Smoker posed risk to NPC compared to never smoker population (OR = 1.48; 95%CI = 0.853 -2.571). Population with homozygous mutant (CA) allele and never smoked had slightly higher risk of NPC (OR= 0.64; 95% CI = 0.328-1.256) compare to people who are ever smoked (OR=0.5; 95% CI =0.185 - 1.354). Likewise, population who has heterozygote mutant (AA) allele and never smoked has high risk of NPC (OR= 1.70; 95% CI = 0.572 - 5.068) compared to people who are ever smoked which has protective effect (OR =0.2; CI =0.034 - 1.174). Conclusion: CA genotype and AA genotype on CLPTM1L/TERT rs31489 showed protective effect towards NPC among male in Yogyakarta. Smoking habit increased the risk of NPC among male in Yogyakarta. Smoking showed protective effect towards NPC among male in Yogyakarta who had CA and AA genotype on CLPTM1L/TERT rs31489. AA genotype on CLPTM1L/TERT rs31489 increased the risk of nasopharyngeal carcinoma among male who never smoke in Yogyakarta. Keywords: nasopharyngeal carcinoma, CLPTM1L/TERT polymorphism, smoking habit, ARMS-PCR

Kata Kunci : nasopharyngeal carcinoma, CLPTM1L/TERT polymorphism, smoking habit, ARMS-PCR