Background: Cytochrome P450 2A6 (CYP2A6) is an enzyme responsible for the metabolism of tobacco-specific nitrosamines leading to the generation of the ultimate carcinogenic forms and the metabolism of nicotine. We here report that the genetic polymorphism of human CYP2A6 involving whole-gene deletion, CYP2A6^*4, is associated with primary lung cancer and the overall survival of patients.

Methods: We prepared genomic DNA samples from 387 Japanese patients with primary lung cancer and analyzed the whole-gene deletion genotype CYP2A6^*4 using a rapid genetic testing method we developed in this study. We analyzed the association of CYP2A6^*4 and NRF2 with overall survival.

Results: Patients harboring wild-type CYP2A6 genotype (^*1/^*1 or ^*1/^*4) and CYP2A6^*4/^*4 numbered 380 (98.2%) and 7 (1.8%), respectively. In a univariate analysis of factors that correlate with clinicopathological features, the frequency of the CYP2A6^*4/^*4 genotype was significantly higher in males than in females (P=0.025), in patients with adenocarcinoma than in those with non-adenocarcinoma (P=0.001), and in nonsmokers than in smokers (P=0.007). In a multivariate logistic analysis,the CYP2A6^*4/^*4 genotype was not associated with gender or smoking behavior. Interestingly, lung cancer patients carrying CYP2A6^*4/^*4 genotype and NRF2 SNP heterozygous (c.−617C/A) or wild-type homozygous (c.−617C/C) alleles exhibited remarkable survival (85.7%) of over 1,500 days after surgical operation. Analysis of male smokers showed that CYP2A6^*4/^*4 was associated with favorable survival outcome in patients with adenocarcinoma.

Conclusions: These results suggest that the CYP2A6^*4 is associated with lung cancer among Japanese population and is a potential prognostic biomarker for assessing overall survival of patients with lung cancer undergoing resection.

Objective: A policy survey regarding the development of hospital formulary and promotion of appropriate drug use in hospital settings was conducted.

Methods: We have conducted a similar survey every five years since 2000 to monitor hospital policy changes. This year, we selected 500 hospitals with 200 or more beds from a list of 2,583 national hospitals for 2015. A stratified random sampling method was used to identify 250 hospitals that adopted the diagnosis procedure combination (DPC)-based payment system and those that did not (250 non-DPC hospitals). Questionnaires consisting of eight items were posted to individuals who had primary responsibility of drug management, during a study period from November 2015 to January 2016.

Results: A total of 175 responses was returned (overall response rate 35%), with response rates of 42% for DPC hospitals and 28% for non-DPC hospitals (including general and mental hospitals). Inclusion of generic drugs in hospital formulary increased by 10 points from 10% in the 2010 survey. Approximately 85% of the hospitals developed their own formulary lists. According to the responses, the most important factors to select formulary drugs were effectiveness, safety, novelty, quality, formulation, price and cost-effectiveness. This trend was almost the same as that reported in the 2010 survey. Eighty-nine percent of DPC hospitals, 73% of general hospitals, and 45% of mental hospitals had specific criteria to select formulary drugs. Many hospitals reported that generic drugs were added to the formulary immediately after they became available in the market.

Conclusion: The results of this survey suggested that many hospitals became more cost-conscious due to social pressure of cutting medical expenditure. The findings that many hospitals already developed formulary lists, had standardized formulary review process, and switched to generic drugs showed increased awareness of appropriate drug choices and uses. However, very few hospitals introduced cost-effectiveness analysis in the review process, and it might take time before this analysis becomes commonly used.