Genetic variants of the XRCC7 gene involved in DNA repair and risk of human bladder cancer

Objective:   To investigate the association between the polymorphisms of the KU70 and X-ray repair cross complementing group 7 ( XRCC7 ) genes and the risk of bladder cancer.
Methods:   This hospital-based case-control study included 213 patients with newly diagnosed bladder transitional cell carcinoma and 235 cancer-free controls frequency-matched by age and sex. Two polymorphisms, KU70 and XRCC7, using a method involving polymerase chain reaction-restriction fragment length polymorphism were genotyped.
Results:   The risk of bladder cancer decreased in a dose–response manner as the number of XRCC7 6721G alleles increased (adjusted odds ratio [OR] = 0.70, 95% confident interval [CI] = 0.47–1.03 for 6721GT and OR = 0.31, 95% CI = 0.10–0.99 for 6721GG; P _trend = 0.013). However, when we used 6721 (GT + GG) as the reference, we found a statistically significant increased risk of bladder cancer associated with the 6721TT genotype (OR = 1.53, 95% CI = 1.04–2.25). In the stratification analysis, this increased risk was more pronounced among subgroups of patients aged >65 years (OR = 2.27; 95% CI = 1.25–4.10) and ever smokers (OR = 2.06, 95% CI = 1.15–3.68). Furthermore, we observed a 3.24-fold increased risk (95% CI = 1.35–7.78) for smokers aged >65 years carrying 6721TT genotype compared with those carrying the 6721 (GG + GT) genotype. However, the KU70 −61C > G polymorphism was not associated with a significantly increased risk of bladder cancer.
Conclusions:   The XRCC7 but not the KU70 polymorphism appears to be involved in the etiology of human bladder cancer. Larger studies with more detailed data on environmental exposure are needed to verify these initial findings.     

Independent risk factors for renal damage in a series of primary vesicoureteral reflux: A multivariate analysis

Aim:   The aim of this study was to investigate risk factors associated with different extents of renal parenchyma involvement in a paediatric series of primary vesicoureteral reflux (VUR).
Methods:   A total of 549 patients with VUR were analyzed. The variable of interest was renal scar, assessed by technetium-99m dimercaptosuccinic acid scan, and classified into three subtypes: focal scar, multiple cortical scarring and diffuse scars with a contracted renal unit. The multinomial regression model was applied to identify independent variables associated with each subtype of renal damage.
Results:   After adjustment, four variables remained independently associated with a contracted renal unit: reflux grades III–V (odds ratio (OR) = 9.7; 95% confidence interval (CI) = 4.1–21.0), age at diagnosis (OR = 3; 95% CI = 1.6–5.1), unilateral reflux (OR = 2.1; 95% CI = 1.2–3.8), and male sex (OR = 2; 95% CI = 1.1–3.8). Two variables were associated with multiple scars: reflux grades III–V (OR = 13.8; 95% CI = 7.4–26.0) and age at diagnosis (OR = 1.9; 95% CI = 1.2–3.0). Two variables were associated with a focal scar: reflux grades III–V (OR = 7.9, 95% CI CI = 3.8–16.4) and male sex as a protective factor (OR = 0.5; 95% CI = 0.25–1.0).
Conclusion:   Our findings suggest that the development of a contracted renal unit is probably due to congenital malformation, more commonly observed in male infants with high-grade reflux.     

XPC gene polymorphisms and risk of idiopathic azoospermia or oligozoospermia in a Chinese population

A retrospective case–control study was carried out in the Han-Chinese population to determine the polymorphisms of xeroderma pigmentosum complementation group C ( XPC ) gene on the risk of idiopathic azoospermia or oligozoospermia. The Ala499Val (C>T) and Lys939Gln (A>C) polymorphism of XPC gene were genotyped by polymerase chain reaction-restriction fragment length polymorphism in three groups of infertile men (172 patients of azoospermia, 25 patients of severe oligozoospermia, 55 patients of oligozoospermia) and 228 fertile men. Increased risk of idiopathic azoospermia, but not oligozoospermia was associated with the XPC variant genotypes of Ala499Val (C>T) [adjusted odds ratio (OR) = 1.67, 95% confidence interval (CI) = 1.04–2.68 for CT heterozygote and adjusted OR = 2.03, 95% CI = 1.10–3.75 for TT homozygote] compared with CC homozygous wide-type. The Lys939Gln (A>C) polymorphism was not related to spermatogenic failure. The combined risk alleles analysis and haplotype analysis showed that ORs increased as the number of the risk alleles increased and the 499T-939C haplotype had a significantly increased risk of idiopathic azoospermia (OR = 7.97; 95% CI = 3.51–18.07) compared with other haplotypes. The results suggest that XPC Ala499Val (C>T) polymorphism is correlated with high risk of idiopathic azoospermia in the Han-Chinese population.     

Genetic polymorphisms of CYP1A1, CYP2E1, GSTM1, and GSTT1 associated with head and neck cancer

BACKGROUND: Alcohol intake and tobacco smoke, in addition to other environmental and genetic factors, have been associated with head and neck cancer. We evaluated the role of metabolic enzyme polymorphisms on the risk of head and neck cancer in a hospital-based case-control study. METHODS: CYP1A1MspI, CYP2E1PstI, GSTM1, and GSTT1polymorphisms were evaluated in 103 histologically confirmed head and neck cancer cases and 102 controls by means of polymerase chain reaction-restriction fragment length polymorphism methods. RESULTS: GSTM1null increased the risk of head and neck cancer (odds ratio [OR], 2.2; 95% confidence interval [95% CI], 1.24-3.79), oral cancer (OR, 2.8; 95% CI, 1.28-5.98), and pharyngeal cancer (OR, 2.2; 95% CI, 1.08-4.63). CYP2E1PstI polymorphism indicated a risk for oral cancer (OR, 3.6; 95% CI, 1.29-11.56). The joint effect of GSTM1 null and CYP1A1 polymorphism increased the risk of head and neck cancer (OR, 2.4; 95% CI, 1.13-5.10). CONCLUSIONS: GSTM1 null alone or associated with CYP1A1 increased the risk of head and neck cancer; the CYP2E1PstI mutated allele increased the risk for only oral cancer.     

The influence of CTLA‐4 single nucleotide polymorphisms on acute kidney allograft rejection in Turkish patients

Cytotoxic T‐lymphocyte antigen‐4 (CTLA‐4) is a cell surface protein, which down‐regulates the immune response at CTLA‐4/CD28/B7 pathway. We aimed to investigate the influence of the ?318C/T, +49A/G, ?1661A/G and CT60A/G, and CTLA‐4 gene polymorphisms on acute rejection of kidney allograft in Turkish patients. The study design was a case–control study that consists of three groups: Group 1 (n = 34) represented the kidney transplant (Ktx) recipients who experienced acute rejection, Group 2 (n = 47) was randomly assigned Ktx recipients without acute rejection, and Group 3 (n = 50) consisting of healthy volunteers to evaluate the normal genomic distribution. The polymerase chain reaction–restriction fragment length polymorphism technique was used to determine the polymorphisms. Genotype and allele frequencies among three groups denoted similar distributions for +49A/G, ?1661A/G, and CT60A/G. Conversely, ?318C/T genotype was three times more frequent in the acute rejection group than in the non‐rejection group (OR = 3.45; 95%CI = 1.18–10.1, p = 0.015) and two times more frequent than the healthy control group (OR = 2.45; 95% CI = 0.98 – 6.11, p = 0.047). Additionally, having a T allele at ?318 position was significantly associated with acute rejection (0.147 vs. 0.043, OR = 3.45; 95% CI = 1.13–10.56, p = 0.02). 318C/T gene polymorphism and T allelic variant were found to be associated with increased acute rejection risk in Turkish kidney allograft recipients.     

生物转化酶基因多态性与前列腺癌易感性的研究

目的 探讨生物转化酶类细胞色素P450（CYP）基因CYP1A1m1、m2和谷胱甘肽转硫酶（GST）M1基因多态性与前列腺癌易感性的关系。方法 采用寡核苷酸芯片对83例前列腺癌患者（前列腺癌组）和115例非前列腺癌对照者（对照组）的中国汉族人基因组DNA进行CYP1A1、GSTM1基因多态性分析。结果 GSTM1缺失型在前列腺癌组和对照组均为48例（57．8％,41．7％）,两组比较差异有统计学意义（X^2=4．99,P=0．025）,GSTMl缺失型使患前列腺癌的危险度增加1．9倍（95％CI=1．10～3．40）。GSTM1缺失型随着前列腺癌的分期、分级的提高,其相对危险度明显提高。前列腺癌组CYP1A1基因的两个多态位点m1、m2基因型频率和等位基因的频率与对照组相比均无统计学意义（P〉0．05）。结论 中国汉族人群GSTM1缺失型可能与前列腺癌的发病风险相关,与前列腺癌的分级、分期有关,对临床预测前列腺癌预后可能有一定意义。     

Polymorphism of cytochrome P450 2B6 and prostate cancer risk: A significant association in a Japanese population

Objectives:   To explore whether Lys262Arg polymorphism of the Cytochrome P450 2B6 (CYP2B6) gene could act as a genetic marker for prostate cancer risk among Japanese men.
Methods:   A total of 350 patients with sporadic prostate cancer and 328 controls were examined. A single nucleotide polymorphism with non-synonymous amino acid change located at Lys262Arg of the CYP2B6 gene was genotyped using a TaqMan assay.
Results:   The frequency of the Arg/Arg genotype among prostate cancer patients was significantly higher than that among the controls ( P  = 0.027). The frequency of the G allele of the Lys262Arg polymorphism was also significantly higher in prostate cancer patients than in the controls (30.4% vs 24.8%, P  = 0.025). Patients with the Lys/Arg plus Arg/Arg genotypes carried a low Gleason score more frequently than those with the Lys/Lys genotype ( P  = 0.042). The frequency of the G allele of the Lys262Arg polymorphism was significantly higher in the low Gleason score group than that in the high Gleason score group (34.3% vs 26.8%, P  = 0.038).
Conclusions:   Lys262Arg polymorphism of the CYP2B6 gene may be a genetic marker for evaluating the risk of sporadic prostate cancer in native Japanese men.     

Association of genetic polymorphism of glutathione S-transferase (GSTM1, GSTT1, GSTP1) with bladder cancer susceptibility

The glutathione-S-transferases (GSTs) comprise a class of enzymes that detoxify carcinogenic compounds by conjugating glutathione to facilitate their removal. Polymorphisms in GSTM1, GSTT1, and GSTP1 genes have been related to risk for bladder cancer. Studies focusing on GSTs gene variants relationship with the risk of bladder cancer have produced conflicting and inconsistent results. We examine the association between genetic polymorphism of glutathione S-transferase P1, GSTM1, GSTT1 genes and development of bladder transitional cell carcinoma (TCC). The study population consisted of 166 histologically confirmed male bladder TCC cases and 332 healthy male controls. Genotyping was done using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method and also investigated combined gene interactions. The GSTP1 Val/Val genotype was significantly associated with bladder cancer (OR = 4.32, 95% CI: 2.64–6.34), whereas the association observed for GSTM1 null (OR = 1.32, 95% CI: 0.82–2.62; P = 0.67) and GSTT1 null genotype (OR = 1.18, 95% CI: 0.79–1.67; P = 0.74) did not reach statistical significance. There was a significant multiple interaction between GSTM1, GSTT1, and GSTP1 genotypes in risk of bladder cancer (P for interaction = 0.02). The risk associated with the concurrent presence of GSTM1 positive and GSTP1 Ile/Val or Val/Val (OR = 3.71, 95% CI: 2.34–5.54) and GSTT1 positive and GSTP1 Ile/Val or Val/Val (OR = 2.66, 95% CI: 1.54–4.72) was statistically significant. Patients carrying GSTP1 Val/Val genotype were at increased risk for developing high-grade (OR = 7.68, 95% CI: 4.73–19.25) and muscle invasive (OR = 10.67, 95% CI: 6.34–21.75) bladder cancer. High risk for bladder TCC also was observed with respect to combined GSTT1 null/GSTP1 Ile/Val or Val/Val (OR = 4.76, 95% CI: 2.68–18.72) and GSTM1 null/GSTT1 null/GSTP1 Ile/Val or Val/Val (OR = 6.42, 95% CI: 4.76–14.72) genotype variant. This study suggests that the GSTP1 polymorphism and its combination with GSTM1, and GSTT1 may be associated with bladder cancer susceptibility in the Iranian population. Further confirmation in large population-based studies is needed.     

The investıgatıon of GSTT1, GSTM1 and SOD polymorphism in bladder cancer patıents

Glutathione S transferases (GSTT1, GSTM1, GSTP1) are enzymes that activate the detoxification of endogenous and exogenous agents. The genetic polymorphism in these genes may change the response of individuals to environmental toxicants. The genetic polymorphisms of GSTT1, GSTM1, GSTP1 have been studied extensively in the determination of individual cancer risks. Some studies showed a strong relationship between polymorphism of GSTs and superoxidedismutase enzymes. Using the polymerase chain reaction (PCR) the prevalence of genetic polymorphisms of GSTT1, GSTM1 and MnSOD (Manganese Superoxide Dismurase) was investigated in 104 cases and controls to seek any association with the risk of bladder cancer. The frequency of GSTT1 +/+ polymorphism was 65% (33/51) in the cases and 79% (42/53) in the controls. The frequency of the GSTM1 +/+ polymorphism was 33% (17/51) in the cases and 58% (31/53) in the controls. The frequency of the GSTM1 null genotype was 42% (22/53) in the controls and 68% (34/51) in the patients. The frequency of the SOD AA genotype was 36% (17/51) in the cases and 33% (19/53) in the controls. There was no association between the GSTT1 and SOD polymorphism and bladder cancer incidence. The incidence of the GSTM1 null genotype was increased in bladder cancer patients compared to controls (OR = 1.755, 95% CI = 1.119–2.751).     

Polymorphisms of N-acetyltransferase 2, glutathione S-transferase mu and theta genes as risk factors of bladder cancer in relation to asthma and tuberculosis

PURPOSE: We investigated whether the polymorphisms of N-acetyltransferase 2 (NAT2), glutathione S-transferase-mu (GSTM1) and glutathione S-transferase-theta (GSTT1) genes were risk factors of bladder cancer among Korean people in relation to other risk factors. MATERIALS AND METHODS: In this case-control investigation of 113 patients with primary bladder cancer and 221 control subjects, we compared the association of bladder cancer with genetic polymorphisms of NAT2, GSTM1 and GSTT1, demographic characteristics, smoking status, and medical histories in a molecular epidemiological way. RESULTS: The risk of bladder cancer was significantly increased in patients with a medical history of tuberculosis (OR 3.61, 95% CI 1.57 to 8.26) and bronchial asthma (OR 4.15, 95% CI 1.61 to 10.75), while smoking history turned out to be insignificant. GSTM1 null genotype was a significant risk factor of bladder cancer (OR 1.81, 95% CI 1.12 to 2.93). On the other hand, slow acetylator and GSTT1 genotypes were insignificant. Also, we could not find any association between GSTM1, GSTT1, slow acetylator genotypes and bladder cancer risk among smokers. The rapid acetylator, GSTM1 null and GSTT1 null genotypes with a medical history of asthma or tuberculosis combinations were significant risk factors in Korean subjects. CONCLUSIONS: Among Korean subjects, GSTM1 null genotype was a significant risk factor for bladder cancer. The reason why bronchial asthma and tuberculosis are risk factors in Korean subjects is yet unknown, but a variety of factors, including enzyme activities for detoxification, medication for these diseases and immunological background might be involved.     

GSTA1, GSTM1, GSTP1, and GSTT1 polymorphisms and susceptibility to smoking-related bladder cancer: A case-control study

ObjectivesGlutathione S-transferases (GSTs) are a family of enzymes involved in detoxification. Genes encoding for GSTA1, GSTM1, GSTP1, and GSTT1 proteins are polymorphic, which can result in complete or partial loss of enzyme activity. Previous studies have associated polymorphisms of GSTA1, GSTM1, and GSTP1 genes with a higher risk of bladder cancer, but this is still controversial. Potential role of GSTA1 polymorphism in susceptibility to bladder cancer in Whites is lacking. We examined association between GSTA1, GSTM1, GSTP1, and GSTT1 gene variants and bladder cancer risk and evaluated whether they were modified by smoking.Materials and methodsA hospital-based case-control study recruited 201 incidence cases and 122 age-matched controls. Deletion polymorphism of GSTM1 and GSTT1 was identified by polymerase chain reaction method. Single nucleotide polymorphism of GSTA1 and GSTP1 was identified by restriction fragment length polymorphism method. Uniconditional multivariate logistic regression was applied to model association between genetic polymorphisms and bladder cancer risk, as well as effect modification by smoking.ResultsNo significant difference was observed in the distributions of GSTM1, GSTT1, GSTA1, and GSTP1 gene variants between patients and controls. None of the examined polymorphisms was significantly associated with bladder cancer risk independently. The results of gene–smoking interaction analyses indicated a significant combined effect of smoking and all common GST polymorphisms tested (P for trend = 0.001). However, the most significant effect on bladder cancer risk was observed in smokers carrying lower activity GSTA1-AB/BB and GSTM-null genotype (OR = 3.5, P < 0.05) compared with GSTA1-AA and GSTM1-active non-smokers. Overall, the risk observed did not significantly differ with respect to quantity of cigarettes smoked. However, heavy smokers with GSTM1-null genotype had 2 times higher risk of bladder cancer than GSTM1-null light smokers (OR = 4.8 vs. OR = 2.0) when GSTM1-active non-smokers served as reference group. Smokers carrying both GSTM1-null and GSTA1-AB + BB genotypes exhibited the highest risk of bladder cancer (OR = 2.00, P = 0.123).ConclusionsNull or low-activity genotypes of the GSTA1, GSTM1, GSTT1, and GSTP1 did not contribute independently towards the risk of bladder cancer in our patients. However, in association with smoking, both low activity GSTA1 and GSTM1-null genotype increase individual susceptibility to bladder cancer.     

Glutathione S-transferase gene polymorphisms (GSTM1, GSTT1, GSTP1) and prostate cancer: a case-control study in Tehran, Iran

We evaluated the relationship between polymorphisms in the glutathione S-transferases (GSTs) GSTM1, GSTT1 and GSTP1 genes and prostate cancer (PCa). PCR-restriction fragment length polymorphism assay was used to genotype the GSTM1, GSTT1, and GSTP1 polymorphisms in 168 PCa cases and 336 frequency matched controls. The GSTM1 null, and GSTT1 null genotypes were associated with an increased odds ratio (OR) for PCa (OR=3.28, 95% confidence interval (CI): 2.47-5.64; P=0.005, and OR=3.21, 95% CI: 2.52-5.64; P=0.005, respectively) (Pcorrected=0.0062). The frequency of GSTP1 Val/Val genotype was 14.3% in cases compared with 2.4% in controls, this polymorphism thus being associated with a significantly increased risk of PCa (OR=3.72, 95% CI: 1.67-5.65; P=0.002). The risk associated with the concurrent absence of both of the genes (OR=4.8, 95% CI: 2.34-6.78) was greater than the product of risk in men with either null (OR=1.52, 95% CI: 0.82-2.31) genotype combinations (P=0.001, Pcorrected=0.0045). The combination of GSTP1 Ile/Val or Val/Val polymorphism with the GSTT1 null and GSTM1 null type resulted in an OR of 6.21 (95% CI: 4.83-16.87) (P=0.0001, Pcorrected=0.0062). A higher frequency of the GSTM1 null genotype and GSTT1 null genotype was observed in patients with Gleason score >7, with an OR for GSTM1 null 4.67 (95% CI: 3.64-7.62; P=0.001) and with an OR for GSTT1 null 3.62 (95% CI: 2.31-5.74; P=0.004). The results obtained demonstrated that simultaneous presence of three potentially risk alleles (GSTM1 null, GSTT1 null and GSTP1 Val) lead to a significant OR increase for PCa.     

Association of genetic polymorphism of glutathione S-transferase M1, T1, P1 and susceptibility to bladder cancer

OBJECTIVE: Glutathione-S-transferases (GSTs) are active in the detoxification of wide variety of endogenous or exogenous carcinogens. We examined the association of the GST gene polymorphism with sporadic bladder cancer patients in Northern India. MATERIAL AND METHODS: The study constituted of 106 bladder cancer cases and 370 age-matched controls. The GSTT1 and GSTM1 null genotypes were identified by multiplex PCR and GSTP1313 A/G by Polymerase Chain Reaction/Restriction Fragment Length Polymorphism method (PCR/RFLP). RESULTS: We observed non-significant association in null alleles of the GSTM1 (p = 0.611, OR = 1.12, 95% CI = 0.72-1.74 and GSTT1 (p = 0.135, OR = 1.45, 95% CI = 0.89-2.37) with risk of bladder cancer. However, the G/G genotype of the GSTP1 gene polymorphism was highly significant when compared to controls (p=0.000, OR = 7.12, 95% CI = 3.14-16.16). The combined analysis of the three risk genotypes demonstrated further increase in the risk of bladder cancer (p = 0.000, OR = 7.29 95% CI = 2.81-18.93). CONCLUSION: Our study demonstrated that GSTP1313 G/G polymorphism is a strong predisposing risk factor for bladder cancer. Combination of three GST genotypes association exhibiting gene-gene interaction further substantiates the increased risk of bladder cancer.     

CYP1A2, CYP2D6, GSTM1, GSTP1, and GSTT1 gene polymorphisms in patients with bladder cancer in a Turkish population

Genetic differences in the metabolism of xenobiotics have recently been suggested as modifiers of individual susceptibility to bladder cancer (BC). The objective of this study was to investigate the relationship between bladder tumor and variants of cytochrome p450 1A2 (CYP1A2) 734 C → A, cytochrome p450 2D6 (CYP2D6) 1934 G → A, glutathione S-transferase M1, (GSTM1 null), glutathione S-transferase T1 (GSTT1 null), and glutathione S-transferase P1 (GSTP1) I105 V. We investigated the distribution of these polymorphisms in 135 BC patients and in 128 age and sex-matched cancer-free controls. The polymorphisms were analyzed using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) assay and the multiplex PCR method. Genotype and allele frequencies and their associations with BC risk, demographic factors, smoking status, and tumor stage were investigated. The prevalence of GSTT1 null genotype in cases was 23%, compared with 7% in the control group (OR = 3.94, 95% CI = 1.70–9.38, P = 0.001). There was no association between the studied polymorphisms of CYP1A2, CYP2D6, GSTM1, and GSTP1 genes and BC. There was an association between smoking status and BC. These data seem to indicate that GSTT1 gene polymorphism may be associated with BC in the Turkish population studied. Further studies will be needed to clarify the role of such variation in determining susceptibility to BC.     

Heparin-bonded circuits versus nonheparin-bonded circuits: an evaluation of their effect on clinical outcomes

Heparinization of the blood contact surface in cardiopulmonary bypass circuits has been promoted as an important step in the development of open heart surgery. As it decreases the inflammatory response resulting from the extracorporeal circulation, it may have a positive effect on clinical outcomes. This meta-analysis was carried out to examine if heparin-bonded circuits (HBCs) reduce the need for blood products and improve overall clinical outcome. A systematic literature search was performed to identify randomized controlled trials reporting outcomes of HBCs compared with non-HBCs. Primary outcomes assessed were postoperative blood/blood-product transfusion and blood loss. Secondary outcomes included all-cause mortality, acute postoperative myocardial infarction, stroke, re-sternotomy for postoperative bleeding, wound infection, atrial fibrillation, duration of ventilation, intensive care unit (ICU) and hospital-length of stay (LOS). Random effects meta-analytical techniques were applied to identify differences in outcomes between the two groups. Quality of the included studies and heterogeneity were assessed. From an initial review of 762-published studies, 41-randomized trials fulfilled the inclusion criteria, leaving 3434-patients’ data for analysis. HBCs significantly decreased the incidence of blood transfusion required (OR = 0.8; 95% CI = 0.6:0.9, P = 0.004). It also significantly decreased re-sternotomy (OR = 0.6; 95% CI = 0.4:0.8, P = 0.002), duration of ventilation (WMD = −1.3 h; 95% CI = −1.9:−0.6, P < 0.001), ICU-LOS (WMD = −9.3 h; 95% CI = −14.7:−3.9, P < 0.001) and hospital-LOS (WMD = −0.5 day; 95% CI = −0.9:−0.1, P = 0.02). HBCs had no effect on other adverse events evaluated. Although HBCs showed a positive effect on some of the clinical outcomes, we identified only marginal differences for other outcomes. Further evaluation of the cost-effectiveness of this technology is required.     

Androgen receptor gene haplotype is associated with male infertility

The purpose of the current study was to evaluate the importance of androgen receptor ( AR ) gene haplotypes and polymorphic CAG/GGN microsatellites in the aetiology of male infertility. We genotyped six haplotype-tagging single nucleotide polymorphisms and CAG/GGN microsatellites of the AR gene in 112 infertile and 212 control Estonian men. A total of 13 AR haplotypes (HAP1–13) were identified, among which HAP4 was found to confer increased risk for male infertility (OR = 5.15, 95% CI = 1.75–15.15, p  = 0.003). However, infertile patients and controls had similar lengths and distributions of both AR CAG (mean ± SD number of repeats 21.1 ± 2.5 vs . 21.2 ± 2.3, respectively) and GGN (mean ± SD number of repeats 22.5 ± 1.5 vs . 22.4 ± 1.9, respectively) repeats. In addition, HAP2 was associated with more CAG repeats ( r  = 1.17, p  = 0.033) and HAP3 with fewer CAG repeats ( r  = −2.93, p  < 0.001) than the major haplotype HAP1. HAP3 and HAP4 were associated with more GGN repeats ( r  = 1.35, p  = 0.001 and r  = 1.36, p  = 0.002, respectively) than HAP1. In conclusion, our results implicated the AR -HAP4 gene haplotype in increased risk for male infertility, while no association was found between AR CAG/GGN microsatellites and impaired spermatogenesis.     

A germline homozygote deletion of the glutathione-S-transferase Mu1 gene predisposes to bladder cancer

INTRODUCTION AND OBJECTIVES: Numerous studies have shown smoking and specific occupational exposures to be risk factors for bladder cancer. The risk of bladder cancer may be modified by the activity of carcinogen metabolizing enzymes. The glutathione-S-transferase Mu1 enzyme (GSTM1) detoxifies arylepoxides which are formed after exposure to certain polycyclic aromatic hydrocarbons and possibly aromatic amines. Approximately 40% of Caucasians lack GSTM1 activity due to a homozygous deletion of the GSTM1 locus on chromosome 1p13 (GSTM1 0/0 genotype). The aim of this study was to evaluate the combined effect of smoking and GSTM1 genotype on the risk of bladder cancer. MATERIALS AND METHODS: Sixty-one patients with transitional cell carcinoma of the bladder and 69 controls matched for age and sex were enrolled from the outpatient clinic. Lifestyle information was collected with a standardized questionnaire. DNA was extracted from white blood cells. The GSTM1 genotype was determined by a PCR-based method. RESULTS: 92% of the 61 patients had a history of smoking compared with 81% of the controls. There was a significant dose-response relationship for pack-years of smoking (trend test: p = 0.003). The proportion of GSTM1 0/0 genotype among patients was 62% compared with 43% among controls (odds ratio = 2.1; 95% CI 1.1-4. 3). The expected interaction between smoking and GSTM1 genotype was not observed. CONCLUSIONS: This study confirms the findings that a germline homozygous deletion of the GSTM1 gene predisposes to bladder cancer. An interaction with smoking was not found.     

Genetic polymorphisms in the cytochrome P450 1A1 and 2E1 genes, smoking, drinking and prostate cancer susceptibility: A case-control study in a Han nationality population in Southern China

AIM: To investigate the association among the polymorphisms of the cytochrome P450 1A1 and 2E1 genes, smoking, drinking and the risk of prostate cancer (PCa) in a Han nationality population in Southern China. METHODS: A case-control study including 225 PCa patients and 250 age-matched controls was conducted. The six polymorphic sites of the CYP 1A1 and CYP2E1 genes were analysed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) or allele-specific PCR technique using genomic DNA isolated from peripheral blood lymphocytes. RESULTS: We found that the CYP1A1 Val/Val genotype significantly increased the risk for PCa (OR, 2.26; 95% CI, 1.09-4.68). In contrast, the CYP2E1 C1/C2 (OR, 0.67; 95% CI, 0.46-0.99) or C2/C2 genotype (OR, 0.31; 95% CI, 0.10-1.00) significantly decreased the risk. Furthermore, the individuals carrying the CYP1A1 Val allele and the CYP2E1 C1/C1 genotype showed the highest risk (OR, 2.50; 95% CI, 1.45-4.29). Though there was no significant difference with smoking history (P = 0.237) or drinking habit (P = 0.499) between cases and controls, a deep smoking habit (OR, 2.02; 95% CI, 1.28-3.17) and heavy smoking history (OR, 1.61; 95% CI, 1.04-2.50) significantly increased the susceptibility of PCa after stratification by smoking method and accumulative smoking amount. Moreover, both the CYP1A1 Val allele (OR, 2.82; 95% CI, 1.49-5.35) and CYP2E1 C1/C1 genotype (OR, 2.57; 95% CI, 1.31-5.02) had obvious interaction with heavy smoking history that significantly raised the risk. We also discovered a significant interaction between the CYP2E1 C1/C1 genotype and drinking (OR, 1.85; 95% CI, 1.04-3.28). CONCLUSIONS: Individuals carrying the CYP1A1 Val allele or the CYP2E1 C1/C1 genotype with a smoking or drinking habit were at increased risk of PCa, which also showed a positive correlation with exposure dose of tobacco.     

Gene polymorphisms in detoxification enzymes as susceptibility factor for head and neck cancer?

OBJECTIVE: Impaired detoxification of carcinogens found in tobacco smoke appears to increase the risk for tobacco associated cancer. The objective of this study was to investigate concomitant polymorphisms in genes encoding for various detoxification enzymes in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: In 187 patients with HNSCC and in 139 healthy control subjects, the polymorphisms of cytochrome P450 1A1 (CYP1A1), cytochrome P450 2D6 (CYP2D6), and glutathione S-transferase mu1 and Theta (GSTM1, GSTT1) were detected by polymerase chain reaction. RESULTS: No significant association were identified between CYP1A1 and CYP2D6 gene polymorphisms and HNSCC. Patients with laryngeal cancer revealed the GSTM1 null genotype more frequently than did the control subjects (P < 0.05). The coincidence of GSTM1 and GSTT1 null genotype was found twice as great in patients as in control subjects (P < 0.05). CONCLUSIONS: It is assumed that detoxification enzymes are functionally redundant and only the simultaneous deficiency of several detoxification enzymes increase the risk for HNSCC in alcohol- and tobacco-exposed individuals.     

miR-143/145侧翼序列多态性与膀胱癌遗传易感性研究

目的 探讨miR-143/145侧翼序列rs4705342和rs4705343多态性与膀胱癌遗传易感性的关系。方法 采用基于医院的病例对照研究,收集106例膀胱癌患者和162例对照人群外周静脉血样本,TaqMan探针法和聚合酶链反应-限制性长度片段多态性分析rs4705342和rs4705343多态性。结果 rs4705342位点CC基因型和C等位基因显著降低了膀胱癌的发病风险（CC与TT相比,调整OR=0.30,95%CI:0.10～0.88,P=0.018;C与T相比,调整OR=0.60,95%CI:0.40～0.89,P=0.01）。 单倍型分析显示,rs4705342C-rs4705343T单倍型显著降低了膀胱癌的发病风险（OR=0.33,95%CI:0.15～0.74）。结论 miR-143/145侧翼序列rs4705342CC基因型可能是膀胱癌发病的保护因素。