The prognosis of lung cancer remains poor with overall five year survival figures varying between five and 10% worldwide, However, it has been shown that surgery in patients with early stage disease in non-small cell lung cancer can achieve five year survival rates up to 80%, suggesting that early or delay diagnosis can influence prognosis. Nevertheless, studies addressing this have been inconclusive and mostly derived from Western countries.
While evidence indicates that early stage disease has better prognosis, the effect of delay in presentation and treatment of patients with non-small cell lung cancer (NSCLC) on survival is debatable. A retrospective study of 122 Malaysian patients with NSCLC was performed to examine the presentation and treatment delay, and its relation with patient survival. Median (25-75% IQR) interval between onset of symptoms and first hospital consultation (patient delay) and between first hospital consultation and treatment or decision to treat (doctor delay) were 2 (1.0- 5.0) and 1.1 (0.6-2.4) months respectively. The median survival rates in patient delay of <1, 1 to 3, and >3 months were 4.1 (9.9-1.7), 5.1 (10.9-3.2) and 5.7 (12.3-2.1) months respectively (log rank p=0.648), while in doctor delay, <30, 30-60, >60 days, the rates were 4.1 (10.8-1.8), 7.6 (13.7-3.2) and 5.3 (16.0-3.0) months respectively (p=0.557). Most patients presented and were treated in a relatively short time, and delays did not appear to influence survival. This Asian data is consistent with those from Western population, reiterating the need for public health measures that can identify disease early..
In Malaysia, many patients opted out of cancer-specific treatment for various reasons. This study was undertaken to investigate the survival rate of patients with stages I to III non-small cell lung cancer (NSCLC) who opted out of treatment, compared with those who accepted treatment. Case records of 119 patients diagnosed with NSCLC between 1996 and 2003 in two urban-based hospitals were retrospectively examined. Survival status was ascertained from follow-up medical clinic records or telephone contact with patients or their next-of-kin. Median (25-75% IQR) survival rate for 79 patients who accepted and 22 patients who opted out of treatment, were 8.6 (16.0-3.7) and 2.2 (3.5-0.8) months respectively [log rank p< 0.001, Kaplan-Meier survival analysis]. Except for proportionately more patients with large cell carcinoma who declined treatment, there was no significant difference between the two groups in relation with age, gender, ethnicity, tumour stage, and time delays between symptom onset and treatment or decision-to-treat. We concluded that there was a small but significant survival benefit in accepting cancer-specific treatment. The findings imply that there is no effective alternative therapy to cancer-specific treatment in improving survival. However, overall prognosis for patients with NSCLC remains dismal.
Nasopharyngeal carcinoma (NPC) is a multifactorial and polygenic disease with high incidence in Asian countries. Epstein-Barr virus infection, environmental and genetic factors are believed to be involved in the tumorigenesis of NPC. The association of single nucleotide polymorphisms (SNPs) in LPLUNC1 and SPLUNC1 genes with NPC was investigated by performing a two-stage case control association study in a Malaysian Chinese population. The initial screening consisted of 81 NPC patients and 147 healthy controls while the replication study consisted of 366 NPC patients and 340 healthy controls. The combined analysis showed that a SNP (rs2752903) of SPLUNC1 was significantly associated with the risk of NPC (combined P = 0.00032, odds ratio = 1.62, 95% confidence interval = 1.25-2.11). In the subsequent dense fine mapping of SPLUNC1 locus, 36 SNPs in strong linkage disequilibrium with rs2752903 (r(2) ≥ 0.85) were associated with NPC susceptibility. Screening of these variants by electrophoretic mobility shift and luciferase reporter assays showed that rs1407019 located in intron 3 (r(2) = 0.994 with rs2752903) caused allelic difference in the binding of specificity protein 1 (Sp1) transcription factor and affected luciferase activity. This SNP may consequently alter the expression of SPLUNC1 in the epithelial cells. In summary, our study suggested that rs1407019 in intronic enhancer of SPLUNC1 is associated with NPC susceptibility in which its A allele confers an increased risk of NPC in the Malaysian Chinese population.
To identify a gene(s) susceptible to nasopharyngeal carcinoma (NPC), we carried out a genome-wide association study (GWAS) through genotyping of more than 500,000 tag single-nucleotide polymorphisms (SNPs), using an initial sample set of 111 unrelated NPC patients and 260 controls of a Malaysian Chinese population. We further evaluated the top 200 SNPs showing the smallest P-values, using a replication sample set that consisted of 168 cases and 252 controls. The combined analysis of the two sets of samples found an SNP in intron 3 of the ITGA9 (integrin-alpha 9) gene, rs2212020, to be strongly associated with NPC (P=8.27 x 10(-7), odds ratio (OR)=2.24, 95% confidence intervals (CI)=1.59-3.15). The gene is located at 3p21 which is commonly deleted in NPC cells. We subsequently genotyped additional 19 tag SNPs within a 40-kb linkage disequilibrium (LD) block surrounding this landmark SNP. Among them, SNP rs189897 showed the strongest association with a P-value of 6.85 x 10(-8) (OR=3.18, 95% CI=1.94-5.21), suggesting that a genetic variation(s) in ITGA9 may influence susceptibility to NPC in the Malaysian Chinese population.