Elisna Syahruddin

Genetic Polymorphism of CYP2A6 and Its Relationship with Nicotine Metabolism in Male Bataknese Smokers Suffered from Lung Cancer in Indonesia

BACKGROUND: Cytochrome P450 2A6 (CYP2A6) is known as an enzyme which is responsible for the metabolism of chemical compounds. AIM: This study aimed to analyse the relationship between CYP2A6 gene polymorphism with nicotine metabolism rates and lung cancer incidence among smokers of Batak ethnic group in Indonesia. METHODS: This study was a case-control study involving 140 research subjects through a purposive sampling technique from three hospitals in Medan, Indonesia. An examination of nicotine metabolism rates was conducted for all subjects using the 3HC/cotinine ratio parameter with LC-MS/MS technique. The examination of the CYP2A6 gene was performed with PCR-RFLP. Data were analysed with Conditional Logistic Regression test using Epi Info 7.0 software. RESULTS: The allele frequencies of CYP2A6*1A, CYP2A6*1B, and CYP2A6*4A found were 44.3%, 48.9%, and 6.8%, respectively. The *1B allele showed the highest metabolism rate. It is found that slow metabolizer individuals were 5.49 times more likely to develop lung cancer (P = 0.01, 95%CI 1.2-24.8). CONCLUSION: Among the Bataknese smokers studied, the CYP2A6*1B allele was found to be the most common allele and showed the highest rate of nicotine metabolism. However, the results show the insignificant relationship among CYP2A6 genetic polymorphism, nicotine metabolism, and lung cancer incidence.

The Role of CYP2A6 Genetic Polymorphism in Nicotine Dependence and Tobacco Consumption among Bataknese Male Smokers

AIM: This research aimed to analyse the relationship between CYP2A6 gene polymorphism with nicotine dependence and its relation to the number of cigarette consumption among Bataknese smokers. METHOD: This study was a cross-sectional study involving 140 research subjects in Medan, Indonesia. RESULTS: Nicotine dependence rates were found to be significantly associated with the number of cigarette consumption expressed in the Brinkman Index. CONCLUSION: The *1A wild-type alleles have a greater risk of high-very high dependence rate compared to the other variants.

Efficacy of gefitinib and radiotherapy combination in Indonesian patients with lung adenocarcinoma

Abstract Introduction. Combinations of gefitinib and radiotherapy have been observed to have synergistic and anti-proliferative effects on lung cancer in vitro. In the clinical setting, patients who presented with respiratory difficulties such as superior vena cava syndrome (SVCS), radiotherapy should be given immediately to address the emergency while waiting for the results of epidermal growth factor receptor (EGFR) mutation test. However, there has been no study that described the role of radio-therapy in Indonesian patients with EGFR-mutant lung adenocarcinoma. Methods. This preliminary study aimed to evaluate the efficacy and toxicities of gefitinib and radiotherapy combination in lung adenocarcinoma patients in Persahabatan National Respiratory Referral Hospital, Jakarta, Indonesia. Subjects were consecutively recruited between January 2013 and December 2016. Results. Thirty-one lung adenocarcinoma with EGFR mutations were enrolled. Most of them were male (51.61%) with a median age of 54.5 years old (range 38-70 years old). EGFR mutation characteristics were on exon 21 L858R point mutation (61.30%), exon 21 L861Q point mutation (16.12%) and exon 19 deletion (22.58%). Radiotherapy was given at doses between 30-60 Gy. Among these subjects, median progression-free survival (PFS) was 185 days (95%CI; 123.69 – 246.30), 1-year survival rate (1-yr) was 45.2%, and median overall survival (OS) was 300 days (95%CI; 130.94 – 469.06). There were no grade 3/4 hematological and nonhematological toxicities recorded. The most frequent grade 1 and 2 non-hematological toxicities were skin rash, diarrhea, and paronychia that might be related to tyrosine kinase inhibitor (TKI). Conclusion. The combination of TKI with radiation may be considered in EGFR-mutant lung adenocarcinoma subjects.

Uncommon EGFR mutations in cytological specimens of 1,874 newly diagnosed Indonesian lung cancer patients

Purpose We aimed to evaluate the distribution of individual epidermal growth factor receptor (EGFR) mutation subtypes found in routine cytological specimens. Patients and methods A retrospective audit was performed on EGFR testing results of 1,874 consecutive cytological samples of newly diagnosed or treatment-naïve Indonesian lung cancer patients (years 2015–2016). Testing was performed by ISO15189 accredited central laboratory. Results Overall test failure rate was 5.1%, with the highest failure (7.1%) observed in pleural effusion and lowest (1.6%) in needle aspiration samples. EGFR mutation frequency was 44.4%. Tyrosine kinase inhibitor (TKI)-sensitive common EGFR mutations (ins/dels exon 19, L858R) and uncommon mutations (G719X, T790M, L861Q) contributed 57.1% and 29%, respectively. Approximately 13.9% of mutation-positive patients carried a mixture of common and uncommon mutations. Women had higher EGFR mutation rate (52.9%) vs men (39.1%; p<0.05). In contrast, uncommon mutations conferring either TKI responsive (G719X, L861Q) or TKI resistance (T790M, exon 20 insertions) were consistently more frequent in men than in women (67.3% vs 32.7% or 69.4% vs 30.6%; p<0.05). Up to 10% EGFR mutation–positive patients had baseline single mutation T790M, exon 20 insertion, or in coexistence with TKI-sensitive mutations. Up to 9% patients had complex or multiple EGFR mutations, whereby 48.7% patients harbored TKI-resistant mutations. One patient presented third-generation TKI-resistant mutation L792F simultaneously with T790M. Conclusion Routine diagnostic cytological techniques yielded similar success rate to detect EGFR mutations. Uncommon EGFR mutations were frequent events in Indonesian lung cancer patients.

Adenocarcinoma of the lung with positive epidermal growth factor receptor mutation in pregnancy

Lung cancer during pregnancy is a rare condition. We report a case of 28-year-old nonsmoker female, who was admitted to our hospital with massive left pleural effusion in the 21st week of gestation. Chest radiograph showed total left hemithorax opacity with contralateral mediastinal deviation. Pleural biopsy and cytological examination of pleural fluid revealed adenocarcinoma invasion with positive epidermal growth factor receptor mutation status. Cesarean section was performed at 32 weeks of pregnancy, and targeted therapy was given to this patient after delivery. Computed tomography of the thorax showed a mass lesion in the left hemithorax with liver metastases. Unfortunately, the patient died 10 days after delivery.

Pain management in lung cancer

Lung cancer is the leading cause of cancer-related mortality worldwide. Not only burdened by the limited overall survival, lung cancer patient also suffer from various symptoms, such as pain, that implicated in the quality of life. Cancer pain is a complicated and transiently dynamic symptom that results from multiple mechanisms. This review will describe the pathophysiology of cancer pain and general approach in managing a patient with lung cancer pain. The use of opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), and adjuvant analgesia, as part of the pharmacology therapy along with interventional strategy, will also be discussed.