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CYP1A1 , GSTM1 , GSTT1 and NQO1 polymorphisms and colorectal adenomas in Japanese men

World Journal of Gastroenterology 2013年第25期19卷 4023-4030页

作者： Tadamichi Hamachi Osamu Tajima Kousaku Uezono shinji tabata Hiroshi Abe Keizo Ohnaka Suminori Kono Department of Preventive Medicine Graduate School of Medical Sciences Kyushu University Self Defense Forces Fukuoka Hospital Kasuga-shi Self Defense Forces Kumamoto Hospital Department of Geriatric Medicine Graduate School of Medical Sciences Kyushu University

AIM: To investigate the role of functional genetic poly-morphisms of metabolic enzymes of tobacco carcinogens in the development of colorectal adenomas. METHODS: The study subjects were 455 patients with colorectal adenomas and 1052 controls with no polyps who underwent total colonoscopy in a preretirement health examination at two Self Defense Forces hospitals. The genetic polymorphisms studied wereCYP1A1*2A (rs 4646903), CYP1A1*2C (rs 1048943), GSTM1 (null or non-null genotype), GSTT1 (null or non-null genotype) and NQO1 C609T (rs 1800566). Genotypes were determined by the polymerase chain reaction (PCR)-restriction fragment length polymorphism or PCR method using genomic DNA extracted from the buffy coat. Cigarette smoking and other life-style factors were ascertained by a self-administered questionnaire. The associations of the polymorphisms with colorectal adenomas were examined by means of OR and 95%CI, which were derived from logistic regression analysis. Statistical adjustment was made for smoking, alcohol use, body mass index and other factors. The gene-gene interaction and effect modification of smoking were evaluated by the likelihood ratio test. RESULTS: None of the five polymorphisms showed a significant association with colorectal adenomas, nor was the combination of GSTM1 and GSTT1 . A borderline significant interaction was observed for the combination of CYP1A1*2C and NQO1 (P = 0.051). The OR associated with CYP1A1*2C was significantly lower than unity among individuals with the NQO1 609CC genotype. The adjusted OR for the combination of the CYP1A1*2C allele and NQO1 609CC genotype was 0.61 (95%CI: 0.42-0.91). Although the interaction was not statistically significant (P = 0.24), the OR for individuals carrying the CYP1A1*2C allele and GSTT1 null genotype decreased significantly compared with those who had neither CYP1A1*2C allele nor GSTT1 null genotype (adjusted OR: 0.69, 95%CI: 0.49-0.97). Smoking did not modify the associations of the individual

关键词： Colorectal adenoma Smoking Polymorphism CYP1A1 GSTM1 GSTT1 NQO1

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Recovery of serum testosterone following neoadjuvant and adjuvant androgen deprivation therapy in men treated with prostate brachytherapy

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World Journal of Radiology 2015年第12期7卷 494-500页

作者： Hideyasu Tsumura Takefumi Satoh Hiromichi Ishiyama Shuhei Hirano Kenichi tabata shinji Kurosaka Kazumasa Matsumoto Tetsuo Fujita Masashi Kitano Shiro Baba Kazushige Hayakawa Masatsugu Iwamura Department of Urology Kitasato University School of Medicine Department of Radiation Oncology Kitasato University School of Medicine

AIM: To investigate the time course of testosterone(T) recovery after cessation of androgen deprivation therapy(ADT) in patients treated with brachytherapy. METHODS: One-hundred and seventy-four patients treated between June 1999 and February 2009 were studied. Patients were divided into a short-term usage group(≤ 12 mo, n = 91) and a long-term usage group(≥ 36 mo, n = 83) according to the duration of gonadotropin-releasing hormone agonist therapy. Median follow-up was 29 mo in the short-term group and was 60 mo in the long-term ***: Cumulative incidence rates of T recovery to normal and supracastrate levels at 24 mo after cessationwere 28.8% and 74.6%, respectively, in the long-term usage group, whereas these values were 96.4% and 98.8% in the short-term usage group. T recovery to normal and supracastrate levels occurred significantly more rapidly in the short-term than in the long-term usage group(P < 0.001 and P < 0.001, respectively). Five years after cessation, 22.6% of patients maintained a castrate T level in the long-term usage group. On multivariate analysis, lower T levels(< 10 ng/d L) at cessation of ADT was significantly associated with prolonged T recovery to supracastrate levels in the longterm usage group(P = 0.002). CONCLUSION: Lower T levels at cessation of ADT were associated with prolonged T recovery in the longterm usage group. Five years after cessation of longterm ADT, approximately one-fifth of patients still had castrate T levels. When determining the therapeutic effect, especially biochemical control, we should consider this delay in T recovery.

关键词： Androgen deprivation Gonadotropinreleasing hormone agonist Prostate brachytherapy Prostate cancer Testosterone

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