Human papillomavirus infections as a marker to predict overall survival in lung adenocarcinoma.

Human papillomavirus (HPV) has been implicated in multiple cancers, but its significance in lung cancer has remained controversial. As the prevalence of HPV 16/18 infection was higher in lung adenocarcinoma among Taiwanese females, the aim of our study was to evaluate the clinical impact of HPV infections in lung adenocarcinoma. Two hundred and ten patients were enrolled to investigate the associations of HPV status in tumors with clinical characteristics as well as its impact on overall survival. The methods to assess HPV status were by immunohistochemistry for HPV L1 capsid protein and E6 protein and by nested polymerase chain reaction for HPV 16 and HPV 18. HPV infections were identified in 35.2% of patients, and associated with localized and smaller sized tumors (p = 0.022 and p = 0.002, respectively). Patients with HPV infections had a significantly better survival (p = 0.023, by log-rank test) and a significantly reduced mortality risk after adjustments of age, tumor extent, epidermal growth factor receptor (EGFR) mutations status and treatments [adjusted hazard ratio = 0.68, 95% confidence interval (CI) = 0.49-0.96, p = 0.026, by multivariate Cox proportional hazards models]. Specifically, patients with both HPV infections and EGFR mutations had the best survival outcome [1-year survival rate, 68.5% (95% CI = 52.2-4.8%)]. Our findings indicate that HPV infections represent an independent prognostic factor for overall survival in patients with lung adenocarcinoma.

NAT2 fast acetylator genotypes are associated with an increased risk for lung cancer with wildtype epidermal growth factor receptors in Taiwan.

Identifying the risk factors responsible for lung cancer especially for nonsmokers is critical for both its prevention and treatment. Studies have linked the polymorphisms in N-acetyltransferases (NAT2), a key enzyme for metabolism of hydrocarbons, with lung cancer in Asian female nonsmokers. Since a high percentage of lung adenocarcinoma in Asian female nonsmokers contains activating hotspot mutations in epidermal growth factor receptors (EGFR), we hypothesized that NAT2 polymorphisms might represent a risk factor in lung cancer with EGFR mutations. We studied NAT polymorphisms in 117 nonsmall cell lung cancer (NSCLC) patients and in 119 healthy controls and EGFR hotspot mutations in exons 18-21 in 100 of the 117 patients using polymerase chain reactions. NAT2 fast acetylator genotypes were significantly associated with patients with lung cancer (P = 0.04, odds ratio (OR): 1.90, 95% confidence interval (CI): 1.02-3.57). Further analyses revealed that NAT2 fast acetylator genotypes were significantly associated with NSCLC with wildtype EGFR (P = 0.008, OR: 3.16, 95% CI: 1.31-7.63), but not with those with EGFR mutations (P = 0.40). Therefore, NAT2 fast acetylator genotypes are a potential risk factor especially for lung cancer with wildtype EGFR.

Multiple analytical approaches demonstrate a complex relationship of genetic and nongenetic factors with cisplatin- and carboplatin-induced nephrotoxicity in lung cancer patients.

BACKGROUND: Cisplatin and carboplatin cause nephrotoxicity by forming platinum-DNA adducts and lead to cell death. METHODS: One-hundred and sixteen Taiwanese lung cancer patients who received cisplatin or carboplatin more than twice were recruited, and their genotypes were determined. The risk of renal dysfunction, injury to the kidney, failure of kidney function, loss of kidney function, and end-stage kidney disease (RIFLE) criteria were used to evaluate the occurrence of nephrotoxicity. A logistic regression, multiple regression with a classification and regression tree (CART), and the Framingham study risk score were used to analyze interactions between genetic and nongenetic factors in producing platinum-induced nephrotoxicity. RESULTS: ERCC1 118C and TP53 72Arg polymorphisms were associated with increased risks of platinum-induced nephrotoxicity. Other risk factors found included the platinum type, baseline serum creatinine (Scr), coadministration of vinorelbine, and the number of chemotherapy cycles. The overall prediction rate of the CART was 82.7%, with a sensitivity of 0.630 and specificity of 0.896. The Framingham study risk prediction model contained 7 factors. Its prediction rate was 84.5%, with a sensitivity of 0.643 and specificity of 0.909. CONCLUSIONS: Genetic polymorphisms of ERCC1 and TP53 are risk factors for nephrotoxicity. The CART analysis may provide a clinically applicable model to predict the risk of cisplatin- and carboplatin-induced nephrotoxicity.