Visfatin Polymorphisms,Lifestyle Risk Factors and Risk of Oral Squamous Cell Carcinoma in a Cohort of Taiwanese Males

Oral cancer is the eighth greatest generally diagnosed cancer amongst males worldwide and the fourth most generally malignancy amongst Taiwanese males. The pro-inflammatory adipocytokine visfatin promotes tumor growth. Elevated plasma visfatin levels have been identified in patients with oral squamous cell carcinoma (OSCC), although the biological mechanisms underlying the involvement of visfatin in the pathogenesis of OSCC are not well understood. Moreover, no information is available regarding associations between visfatin polymorphisms and carcinogenic lifestyle factors with OSCC. This study, therefore, investigated the effects of four visfatin gene polymorphisms (rs11977021, rs61330082, rs2110385, and rs4730153) and carcinogenic lifestyle factors (betel nut chewing, alcohol consumption and cigarette smoking) on the risk of developing OSCC in 1,275 Taiwanese males with OSCC, and 1,195 healthy males (controls). We also examined the associations between these visfatin genotypes and OSCC histopathological prognostic factors (pathological stage, tumor status, lymph node status, and metastasis). We found that compared with subjects with the CC genotype of SNP rs11977021, those with the CT+TT genotype were less likely to progress OSCC. In addition, an association was found between the rs4730153 variant and lymph node metastasis in the OSCC cohort.     

Structure-Function Analyses of Single Nucleotide Polymorphisms in Human N-Acetyltransferase 1

Human N-acetyltransferase 1 (NAT1) alleles are characterized by one or more single nucleotide polymorphisms (SNPs) associated with rapid and slow acetylation phenotypes. NAT1 both activates and deactivates arylamine drugs and carcinogens, and NAT1 polymorphisms are associated with increased frequencies of many cancers and birth defects. The recently resolved human NAT1 crystal structure was used to evaluate SNPs resulting in the protein substitutions R64W, V149I, R187Q, M205V, S214A, D251V, E261K, and I263V. The analysis enhances knowledge of NAT1 structure-function relationships, important for understanding associations of NAT1 SNPs with genetic predisposition to cancer, birth defects, and other diseases.     

Genetic characterization of Plasmodium falciparum allelic variants infecting mothers at delivery and their children during their first plasmodial infections

IntroductionInfants born to mothers with placental malaria at delivery develop Plasmodium falciparum parasitemia earlier than those born to mothers without placental infection. This phenomenon may be explained by the development of immune tolerance due to exposure to P. falciparum antigens in utero. The hypothesis of this study is that this increased susceptibility might be related to infections by parasites expressing the same blood stage allele’s antigens as those to which the infants were exposed in utero.MethodsThe comparison of P. falciparum msp2 (3D7 and FC27) and glurp gene polymorphisms of infected mothers at delivery to those of their offspring’s infections during infancy was realized and the possible associations of the different polymorphisms with clinical outcomes were assessed. A second approach consisted in the use of a Geographic Information System to determine whether the antigen alleles were homogeneously distributed in the area of study. This was necessary to analyze whether the biological observations were due to high exposure to a particular antigen allelic form in the environment or to high infant permissiveness to the same allelic antigen polymorphism as the placental one.ResultsInfants born to mothers with placental malaria at delivery were more susceptible to infections by parasites carrying the same glurp allele as encountered in utero compared to distinct alleles, independently of their geographic distribution.ConclusionThe increased permissiveness of infants to plasmodial infections with shared placental-infant glurp alleles sheds light on the role that P. falciparum blood stage antigen polymorphisms may play in the first plasmodial infections in infancy.     

The Incidence of Malignant Disease in 1,620 African (Bantu) Gold Miners

Job outlook among men aged 25 to 64 years followed after first myocardial infarction (MI) is examined in a study of incidence and prognosis of coronary heart disease (CHD) conducted by the Health Insurance Plan of Greater New York, Employment status of 470 men with first MI is similar to that of men clinically free of CHD at the start of follow-up: 79% of men with Ml and 83% of CHD-free men are employed at the end of 4 1/2 fears of follow-up. Age and clinical severity of Ml influence rate of return to work and the proportions of men returning, but hypertension is not a significant factor. Blue-collar workers return to work more slowly than white-collar workers. Under age 55, blue-collar workers are more likely to return to changed jobs; among older men, retirement is more common in the blue-collar group.     

药物基因组学研究进展

同一种药物对患有相同疾病的不同患者疗效不同是临床上常见的一种现象 ,以往的观点认为这是由于药代动力学的差异造成的。最近的研究表明 ,药效学原因所产生的差异更为广泛和显著 ,而药效学差异大多源于基因的差异。为此 ,提出了“药物基因组学”这个全新的概念。1　药物遗传学与药物基因组学药物遗传学 (ｐｈａｒｍａｃｏｇｅｎｅｔｉｃｓ)的概念是 2 0世纪5 0年代由ＦｒｉｅｄｒｉｃｈＶｏｇｅｌ[1] 首先提出的 ,它研究包括药物在内的外界化学物质 (尤其是有毒外源物质 )引起机体反应 (主要指毒性和不良反应 )的遗传多样性。在ＲＦＬＰ和…     

雌激素受体基因多态性与乳腺癌的关系

目的：研究雌激素受体α（ESR1）基因单核苷酸多态性（SNPs）与乳腺癌患者临床病理特征和乳腺癌易感性的关系。 方法：运用聚合酶链反应（PCR）和限制性片段长度多态性（RFLP）分析的方法检测193例中国汉族女性乳腺癌患者和71名正常女性对照者ESR1基因上RS2077647位点的基因型,以SPSS 11.0软件卡方检验处理数据。 结果：①RS2077647位点等位基因频率符合Hardy-Weinberg遗传平衡定律;②RS2077647位点的等位基因及基因型与患者年龄、肿瘤大小及PR表达相关,不同年龄组、不同肿瘤大小组和孕激素受体（PR）阴性与阳性组间,RS2077647的等位基因和基因型的频率不同,差异有显著性（P＜0.05）;③RS2077647位点等位基因及基因型频率在乳腺癌人群与正常对照者间分布差异无显著性（P＞0.05）。 结论:RS2077647位点基因的多态性与乳腺癌患者的年龄、肿瘤大小及PR表达相关,与乳腺癌易感性无关。     

新型口服抗凝药的药物基因组学研究进展

新型口服抗凝药（NOAC）在心脑血管血栓疾病的防治中发挥了重要作用。由于参与NOAC体内过程的转运体和代谢酶的基因多态性,不同个体口服相同剂量的NOAC后,其体内药代动力学参数存在差异。相对于药物转运体,药物代谢酶的基因多态性对NOAC的药代动力学性质影响较大,但目前相关研究较少。本文分析总结了基因多态性对NOAC药代动力学性质的影响。     

Association of oestrogen receptor alpha polymorphisms and androgen receptor CAG trinucleotide repeats with male infertility: a study in 109 Greek infertile men

This study was performed to examine the contribution of genetic polymorphism of oestrogen and androgen receptor (AR) genes in male infertility. We have studied in total 173 Greek men, 109 infertile patients and 64 controls (group A). Patients were divided in to three subgroups: group B (n=29) with idiopathic moderate oligospermia, group C (n=42) with azoospermia or idiopathic severe oligospermia and group D (n=38) with azoospermia or oligospermia of various known aetiologies. All patients and controls were genotyped for two polymorphisms of the oestrogen receptor alpha (ERalpha) gene and also for the (CAG)n repeat length polymorphism of the X-linked androgen receptor (AR)gene. The control group had statistically significant difference from group C regarding the XbaI polymorphism of ERalpha gene. Despite the fact that we did not observe any statistically significant differences in the mean and range of the CAG repeat number, the frequency of the higher repeats of the nucleotide repeat sequence (CAG)n of the AR gene was 2-4 times higher in groups B and C compared with the control group A. Our results indicate that both ERalpha and AR gene play significant role in male fertility. It is possible that a synergy may exist between unfavourable genotypes of these two genes in male infertility.     

Single‐nucleotide polymorphisms within the antioxidant defence system and associations with aggressive prostate cancer

What’s known on the subject? and What does the study add? Prior studies have identified potential interaction effects between antioxidant nutrients and germline gene variants with regards to prostate cancer risk. In particular, the rs4880 gene variant in SOD2 (or MnSOD) has been linked to several cancers, including prostate, and appears to interact with antioxidant status and cancer risk. We identified additional variants in SOD2 and SOD1 that may affect risk of prostate cancer, or interact with selenium status to affect prostate cancer risk.

OBJECTIVE

To study the effects of oxidative stress on prostate cancer development as the exact biological mechanisms behind the relationship remain uncertain. We previously reported a statistically significant interaction between circulating selenium levels, variants in the superoxide dismutase 2 gene (SOD2; rs4880), and risk of developing prostate cancer and presenting with aggressive prostate cancer.

PATIENTS AND METHODS

We genotyped men with localized/regional prostate cancer for 26 loci across eight genes that are central to cellular antioxidant defence: glutathione peroxidase (GPX1, GPX4), peroxisome proliferator‐activated receptor γ coactivator (PPARGC1A, PPARGC1B), SOD1, SOD2, and SOD3, and ‘X‐ray repair complementing defective repair in Chinese hamster cell 1’ (XRCC1). Among 489 men, we examined the relationships between genotypes, circulating selenium levels, and risk of presenting with aggressive prostate cancer at diagnosis, as defined by stage, grade and prostate‐specific antigen (PSA) level (213 aggressive cases).

RESULTS

Two variants in SOD2 were significantly associated with the risk of aggressive prostate cancer (rs17884057, odds ratio 0.83, 95% confidence interval 0.70–0.99; and rs4816407, 1.27, 1.02–1.57); men with A alleles at rs2842958 in SOD2 had lower plasma selenium levels (median 116 vs 121.8 µg/L, P= 0.03); and the association between plasma selenium levels and risk of aggressive prostate cancer was modified by SOD1 (rs10432782) and SOD2 (rs2758330).

CONCLUSION

While this study was cross‐sectional and these associations might be due to chance, further research is warranted on the potential important role of antioxidant defence in prostate cancer.     

胰岛素降解酶基因单核苷酸多态性与前列腺癌的关系研究

目的研究胰岛素降解酶(IDE)基因单核苷酸多态性与前列腺癌之间的关系。方法运用TaqMan探针SNP分析法测定192例胰腺癌患者和258例正常对照IDE基因rs4646953和rs2251101两个位点基因型,并分析IDE基因多态性与前列腺癌的关系。结果病例组IDE基因rs4646953位点TT、CT以及CC3种基因型等位基因频率分别为85.4%、14.1%和0.5%;对照组3种基因型等位基因频率分别为88.4%、10.1%和1.6%。病例组rs2251101位点TT、CT以及CC3种基因型频率分别为81.8%、16.7%和1.6%;对照组3种基因型等位基因频率分别为73.6%、23.3%和3.1%。病例组IDE基因rs4646953位点的基因型分布与正常对照组比较未见统计学差异(P=0.348),rs2251101位点病例组CT和CC基因型低于正常对照组(P=0.039)。结论 IDE基因rs2251101位点变异与前列腺癌相关。