DNA repair genes XPD and XRCC1 polymorphisms and risk of end-stage renal disease in Egyptian population

Abstract

DNA repair gene polymorphisms may affect DNA repair capacity and modulate susceptibility to end-stage renal disease (ESRD). We aimed to determine the association of polymorphisms in xeroderma pigmentosum complementation group D (XPD) and X-ray cross-complementing group 1 (XRCC1) with ESRD development. Polymorphisms in XPD codons 312 and 751 and XRCC1 codon 399 were genotyped in 98 patients undergoing hemodialysis and 102 healthy controls using polymerase chain reaction and restriction fragment length polymorphism. Patients having XRCC1-399 Arg/Gln genotype or XRCC1-399 Gln/Gln genotype had a significantly higher risk of ESRD than those with XRCC1-399 Arg/Arg [odds ratio (OR): 2.48; 95% confidence intervals (CI): 1.36–4.52; p?=?0.004 and OR: 4.05; 95% CI: 1.19–13.73; p?=?0.03, respectively]. We also found a significantly higher frequency of the XRCC1 399Gln allele in patients with ESRD than in controls (OR: 2.22; 95% CI: 1.16–4.25; p?=?0.02). Combination of the Arg/Gln or Gln/Gln genotypes of XRCC1 Arg399Gln polymorphism with Asp/Asn or Asn/Asn genotypes of XPDAsp312Asn or with the Lys/Gln or Gln/Gln genotypes of XPD Lys751Gln was significantly associated with the development of ESRD. Haplotypes association showed that association of Gln allele of XRCC1 Arg399Gln polymorphism with the Asn allele of XPDAsp312Asn polymorphism (p?=?0.004) or Gln allele of XRCC1 Arg399Gln polymorphism with the Gln allele of XPD Lys751Gln polymorphism (p?=?0.003) was highly significantly associated with the development of ESRD. This study revealed that XRCC1 Arg399Gln polymorphism may confer increased risk for the development of ESRD. Furthermore, larger studies should be conducted to confirm these results.     

XRCC1 gene polymorphisms and breast cancer risk in different populations: A meta-analysis

We performed a meta-analysis to investigate the role of XRCC1 polymorphisms Arg194Trp, Arg280His and Arg399Gln in breast cancer. The results were pooled in a manner that appropriately reflects a biological model of gene effect using a random effects logistic regression model without multiple comparisons. Forty studies from 31 reports were included with 10 465 cases and 10 888 controls at Arg194Trp, 6156 cases and 5806 controls at Arg280His, and 21 467 cases and 22 766 controls at Arg399Gln. Our analysis found a tendency towards a recessive effect of Arg280His variant in Asian population only (His/His vs. Arg/Arg + Arg/His: OR = 2.27, 95% CI = 0.82, 6.31). An increased breast cancer risk with a recessive effect was also suggested for Arg399Gln variant in Asian population (Gln/Gln vs. Arg/Arg + Arg/Gln: OR = 1.59, 95% CI = 1.22, 2.09) only. These findings suggest that polymorphisms Arg280His and Arg399Gln may modify breast cancer risk differently in Caucasian and Asian populations.     

Association between X-ray repair cross-complementing group 1 Arg399Gln polymorphism and male infertility: An update meta-analysis

Numerous studies concentrate on the association between X-ray repair cross-complementing group 1 (XRCC1) gene polymorphism and male infertility; however, the results remain inconclusive and inconsistent. Hence, this meta-analysis was conducted to get a precise estimation of the correlation. PubMed, Web of Science, Embase, Scopus and China National Knowledge Infrastructure (CNKI) databases were searched to identify the all relevant studies before 3 May 2020. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to assess the strength of the association. Finally, six studies with 1,886 cases and 1,212 controls were included in our study. The result indicated that XRCC1 Arg399Gln polymorphism was significantly associated with male infertility under allelic model (A-allele vs. G-allele: OR = 1.183, p = .003), heterozygote genetic model (AA vs. GA: OR = 1.256, p = .027), recessive genetic model (AA vs. GG + GA: OR = 1.279, p = .012) and dominant genetic model (AA + GA vs. GG: OR = 1.218, p = .026). In addition, in Asian subgroup, statistic correlation remained significant in allelic model (A-allele vs. G-allele: OR = 1.145, p = .025) with rare heterogeneity (I² = 0%). In summary, our meta-analysis suggested that XRCC1 Arg399Gln polymorphism was significantly associated with male infertility and the A-allele might be a risk factor for this disease, especially in Asians.     

Relationship between XRCC1 polymorphisms and susceptibility to prostate cancer in men from Han, Southern China

Aim： To investigate the association among XRCC1 polymorphisms, smoking, drinking and the risk of prostate cancer （PCa） in men from Han, Southern China. Methods： In a case-control study of 207 patients with PCa and 235 cancerfree controls, frequency-matched by age, we genotyped three XRCC1 polymorphisms （codons 194, 280 and 399） using the polymerase chain reaction-restriction fragment length polymorphism （PCR-RELP） method. Results： Among the three polymorphisms, we found that the XRCC1 Arg399Gln variant allele was associated with increased PCa risk （adjusted odd ratio [OR]： 1.67, 95% confident interval [CI]： 1.11-2.51）, but the XRCC1 Arg 194Trp variant allele had a 38% reduction in risk of PCa （adjusted OR： 0.62, 95% CI： 0.41-0.93）. However, there was no significant risk of PCa associated with Arg280His polymorphism. When we evaluated the three polymorphisms together, we found that the individuals with 194Arg/Arg wild-type genotype, Arg280His and Arg399Gln variant genotypes had a significantly higher risk of PCa （adjusted OR： 4.31; 95% CI： 1.24-14.99） than those with three wild-type genotypes. In addition, we found that Arg399Gln variant genotypes had a significant risk of PCa among heavy smokers （adjusted OR： 2.04; 95% CI： 1.03-4.05）. Conclusion： These results suggest that polymorphisms of XRCC1 appear to influence the risk of PCa and may modify risks attributable to environmental exposure.     

XRCC1 Arg399Gln and Arg194Trp polymorphisms in prostate cancer risk: a meta-analysis

Epidemiological studies have evaluated the association between X-ray repair cross-complementing group 1 gene (XRCC1) Arg399Gln and Arg194Trp polymorphisms and risk of prostate cancer (PCa). However, the results from the published studies on the association between these two XRCC1 polymorphisms and PCa risk are conflicting. To derive a more precise estimation of association between the XRCC1 polymorphisms and risk of PCa, we performed a meta-analysis. A comprehensive search was conducted to identify all case-control studies of XRCC1 polymorphisms and PCa risk. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. Overall, we found that both Arg399Gln and Arg194Trp polymorphisms were not significantly associated with PCa risk. However, in stratified analysis by ethnicity, we found that the Arg399Gln polymorphism was significantly associated with PCa risk in Asian population (Gln/Gln vs Arg/Arg: OR=1.46, 95% CI: 1.05-2.03, P=0.03; Gln/Gln vs Arg/Gln+Arg/Arg: OR=1.48, 95% CI: 1.12-1.95, P=0.01). In this meta-analysis, we found that both Arg399Gln and Arg194Trp polymorphisms were not related to overall PCa risk. However, in subgroup analysis we found a suggestion that XRCC1 399Gln allele might be a low-penetrent risk factor for PCa only in Asian men.     

DNA修复基因XRCC1多态与食管癌TNM分期及区域淋巴结转移的相关性研究

目的 研究DNA修复基因XRCC1 Arg194Trp和Arg399Gln多态与食管鳞状细胞癌临床病理TNM分期及区域淋巴结转移的相关性,探讨其对食管癌临床表型的影响.方法 以PCR和PCR-RFLP方法分析了182例食管癌病人的上述基因多态,比较不同TNM分期及区域淋巴结转移的食管癌病人各基因型频率分布的差异.结果 食管癌Ⅱb～Ⅳ期及有区域淋巴结转移病人XRCC1Arg194Trp基因型及Arg399Gln基因型频率与0～Ⅱa期及无区域淋巴结转移病人虽有差别,但无统计学意义.食管癌区域淋巴结转移病人携带XRCC1194Arg/Trp杂合型和399Arg/Arg野生型基因型频率为32.3%,显著高于携带XRCC1194Arg/Arg基因型的20.0%（P=0.01）.结论 DNA修复基因XRCC1多态中携带194变异型基因型和399野生型基因型的病人区域淋巴结转移率较高,病变进展较快,因此与食管癌TNM分期和区域淋巴结转移存在相关型,两者对食管癌病人的预后有影响.     

Uptake of bilateral-risk-reducing-mastectomy: Prospective analysis of 7195 women at high-risk of breast cancer

BackgroundBilateral-Risk-Reducing-Mastectomy-(BRRM) is well described in BRCA1/2 pathogenic variant carriers. However, little is known about the relative uptake, time trends or factors influencing uptake in those at increased breast cancer risk not known to be carriers. The aim of this study is to assess these factors in both groups.MethodsBRRM uptake was assessed from entry to the Manchester Family History Clinic or from date of personal BRCA1/2 test. Follow up was censored at BRRM, breast cancer diagnosis, death or January 01, 2020. Cumulative incidence and cause specific and competing risk regression analyses were used to assess the significance of factors associated with BRRM.ResultsOf 7195 women at ≥25% lifetime breast cancer risk followed for up to 32 years, 451 (6.2%) underwent pre-symptomatic BRRM. Of those eligible in different risk groups the 20-year uptake of BRRM was 47.7%-(95%CI = 42.4–53.2%) in 479 BRCA1/2 carriers; 9.0% (95%CI = 7.26–11.24%) in 1261 women at ≥40% lifetime risk (non-BRCA), 4.8%-(95%CI = 3.98–5.73%) in 3561 women at 30–39% risk and 2.9%-(95%CI = 2.09–4.09%) in 1783 women at 25–29% lifetime risk. In cause-specific Cox regression analysis death of a sister with breast cancer<50 (OR = 2.4; 95%CI = 1.7–3.4), mother<60 (OR = 1.9; 95%CI = 1.5–2.3), having children (OR = 1.4; 95%CI = 1.1–1.8), breast biopsy (OR = 1.4; 95%CI = 1.0–1.8) were all independently associated with BRRM uptake, while being older at assessment was less likely to be associated with BRRM (>50; OR = 0.26,95%CI = 0.17–0.41). Uptake continued to rise to 20 years from initial risk assessment.ConclusionWe have identified several additional factors that correlate with BRRM uptake and demonstrate continued increases over time. These factors will help to tailor counselling and support for women.     

Psychological factors associated with the intention to choose for risk-reducing mastectomy in family cancer clinic attendees

ObjectivesWomen seeking counseling because of familial breast cancer occurrence face difficult decisions, such as whether and when to opt for risk-reducing mastectomy (RRM) in case of BRCA1/2 mutation. Only limited research has been done to identify the psychological factors associated with the decision for RRM. This study investigated which psychological factors are related to the intention to choose for RRM.Materials & methodsA cohort of 486 cancer-unaffected women with a family history of breast cancer completed the following questionnaires prior to genetic counseling: the Cancer Worry Scale, Positive And Negative Affect Scale, Perceived Personal Control Scale, Hospital Anxiety and Depression Scale and State Anxiety Scale and questions regarding socio-demographic characteristics, family history, risk perception and RRM intention. Multivariate logistic regression was used to analyze the relation between psychological factors and women's intention to choose for RRM.ResultsFactors associated with RRM intention were high positive affect (OR = 1.86, 95%CI = 1.12–3.08), high negative affect (OR = 2.52, 95%CI = 1.44–4.43), high cancer worry (OR = 1.65, 95%CI = 1.00–2.72), high perceived personal control (OR = 3.58, 95%CI = 2.18–5.89), high risk-perception (OR = 1.85, 95%CI = 1.15–2.95) and having children (OR = 2.06, 95%CI = 1.21–3.50).ConclusionNegative and positive affects play an important role in the intention for RRM.Furthermore, perceived personal control over the situation is associated with an intention for RRM. In addition to focusing on accurate risk communication, counseling should pay attention to the influence of perceived control and emotions to facilitate decision-making.     

Use of Bisphosphonates and Risk of Breast Cancer

A decreased risk of breast cancer has been reported among patients given bisphosphonates. The present aims were to study potential associations between different antiosteoporosis drugs, including bisphosphonates, and the risk of breast cancer before and after start of treatment and to appraise possible dose–effect relationships. From national Danish registers, all female users of bisphosphonates aged ≥40 years and other drugs against osteoporosis between 1996 and 2006 were identified (n = 87,104). This cohort was compared with a control group, where each patient was matched on age with three nonexposed women from the general population (n = 261,322). Before start of most drugs against osteoporosis an increased risk of breast cancer was seen compared to controls (e.g., adjusted OR = 1.09, 95% CI 1.04–1.16 for alendronate). This excess risk was higher in younger women (e.g., OR = 4.48, 95% CI 2.98–6.75 for alendronate in women ≤50 years) and disappeared in women older than 70 years (e.g., OR = 0.95, 95% CI 0.88–1.01 for alendronate). In contrast, a decreased risk of breast cancer was seen after start of alendronate (HR = 0.53, 95% CI 0.38–0.73), etidronate (HR = 0.80, 95% CI 0.73–0.89), and raloxifene (HR = 0.53, 95% CI 0.38–0.73). No dose–response relationship was present for alendronate and etidronate, whereas a decreasing risk was seen with increasing daily dose of raloxifene. Bisphosphonate treatment in women was associated with a reduced risk of breast cancer. However, no causal relationship seemed to be present.     

Polymorphism Arg290Arg in Esophageal-Cancer-Related Gene 1 (ECRG1) is a Prognostic Factor for Survival in Esophageal Cancer

Background  Esophageal cancer is one of the most frequent cancers worldwide and is associated with poor outcome. Besides clinicopathological data, few prognostic molecular markers exist. Esophageal-cancer-related gene1 (ECRG1) short tandem repeats are associated with higher risk for developing esophageal squamous cell carcinoma. The aim of the present study was to evaluate the impact of DNA polymorphisms in the coding region of ECRG1 in esophageal carcinoma. Methods  Genomic DNA of 107 patients with esophageal cancer that underwent complete surgical resection between 1997 and 2005 was extracted. DNA was analyzed for ECRG1 polymorphisms Arg290Arg, Arg290Gln, and Gln290Gln by PCR and gel electrophoresis. Polymorphisms were correlated with survival data by the Kaplan–Meier method, multivariate Cox regression analysis, and odds ratio were determined. For all variables, cross tables were generated, followed by calculation of the p value by using the chi-square test/Fisher-exact test. Results  Follow-up data of 102 patients with esophageal cancer were available after complete surgical resection for a median follow-up time of 24.3 months. Polymorphism Arg290Arg was found in 47 patients (46.1%), Arg290Gln in 48 patients (47.0%), and Gln290Gln in seven cases (6.9%). Arg290Arg polymorphism was significantly associated with reduced overall survival (p = 0.01) and tumor-free survival (p = 0.01) by the log-rank test. Multivariate regression analysis by Cox revealed polymorphism Arg290Arg to be a significant prognostic factor for survival (p = 0.012). Conclusions  Polymorphism Arg290Arg in ECRG1 is associated with poor clinical outcome after complete surgical resection in patients with esophageal cancer.     

苏、皖地区汉族人群DNA修复基因XRCC1 Arg399Gln多态性与前列腺癌易感性的关系

目的:研究中国苏、皖汉族人群DNA修复基因X线修复交叉互补基因1(X-ray repair cross complementing group 1,XRCC1)Arg399Gln多态性,并探讨其在吸烟、饮酒与前列腺癌易感性关系中的影响。方法:采用病例-对照研究,提取207例前列腺癌患者(病例组)和235例非肿瘤、非前列腺疾病患者(对照组)外周血中基因组DNA,应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析病例组和对照组的XRCC1基因Arg399Gln位点的多态性,比较不同基因型与前列腺癌易感性的关系,并探讨吸烟、饮酒等因素在其中的影响。结果:XRCC1第399密码子Arg/Gln基因型的个体其前列腺癌发病风险是Arg/Arg基因型的1.55倍(OR=1.55,95%CI:1.01~2.39),携带399Gln等位基因(Arg/Gln及Gln/Gln)的个体发生前列腺癌的风险性是Arg/Arg基因型的1.61倍(OR=1.61,95%CI:1.07~2.44)。在重度吸烟(吸烟指数≥20)人群中,携带399Gln等位基因的个体发生前列腺癌的风险性是Arg/Arg基因型的1.94倍(OR=1.94,95%CI:1.02~3.71)。在浅吸烟(吸烟仅入嘴中)人群中,携带399Gln等位基因的个体发生前列腺癌的风险性是Arg/Arg基因型的2.44倍(OR=2.44,95%CI:1.02~5.80)。结论:XRCC1 Arg399Gln位点多态性可能对前列腺癌遗传易感性产生影响,Arg/Gln、Gln/Gln可能是前列腺癌的易感基因型,并和吸烟在前列腺癌的发病中有一定的协同作用。     

Incidence,risk factors and clinical implications of postoperative urinary tract infection in geriatric hip fractures

IntroductionPostoperative urinary tract infection (UTI) is common in geriatric patients; however, little is known about the impact of UTI in orthopedic trauma. The present study was designed to determine the risk factors and clinical impact of postoperative urinary tract infection (UTI) in acute geriatric hip fractures.Patients and methodsGeriatric patients (≥65 years of age) undergoing hip fracture surgery were identified within the American College of Surgeons National Surgical Quality Improvement Program between 2016 and 2019. Patients presenting with UTI at the time of surgery were excluded. Baseline characteristics and outcomes were compared between patients with and without postoperative UTI. Multivariate logistic regression was performed, controlling for potential confounders.ResultsA total of 46,263 patients included in the study. Overall, 1,397 (3.02%) patients had postoperative UTI. Patients who developed postoperative UTI had higher rates of pneumonia (6.44% vs. 3.76%, p < 0.001), DVT (2.22% vs. 1.04%, p < 0.001), sepsis (7.73% vs. 0.62%, p < 0.001), and more frequently experienced postoperative hospital lengths of stay exceeding 6 days (37.94% vs. 20.33%, p < 0.001). Hospital readmission occurred more frequently in patients with postoperative UTI (24.55% vs. 7.85%, p < 0.001), but surprisingly, these patients had a lower mortality rate (1.36% vs. 2.2%, p < 0.001). Adjusted analysis demonstrated the following variables associated with postoperative UTI: age ≥ 85 (OR = 1.37, 95%CI = 1.08 - 1.73), ASA class ≥ 3 (OR = 1.59, 95%CI = 1.21 – 2.08,), chronic steroid use (OR = 1.451, 95%CI = 1.05 - 1.89), blood transfusion (OR = 1.24, 95%CI = 1.05 - 1.48), and >2 days delay from admission to operation (OR = 1.37, 95%CI = 1.05 - 1.79). Postoperative UTI was significantly associated with sepsis (OR = 7.65, 95%CI = 5.72 – 10.21), postoperative length of stay >2 days (OR = 1.83, 95%CI = 1.07 – 3.13), and readmission (OR = 3, 95%CI = 2.54 – 3.55).ConclusionsIn our study, postoperative UTI was found in 3% of geriatric hip fracture patients. Predictors of postoperative UTI were age ≥ 85, ASA class ≥ 3, chronic steroid use, blood transfusion, and time to operation > 2 days from admission. Results showed that postoperative UTI is independently associated with sepsis, postoperative length of stay beyond 2 days, and hospital readmission. To diminish the risk of UTI and its consequences, we recommend operating geriatric hip fractures in 24–48 hours after admission.     

The prevalence of radiographic vertebral fractures in Latin American countries: the Latin American Vertebral Osteoporosis Study (LAVOS)

Summary  In the first population-based study of vertebral fractures in Latin America, we found a 11.18 (95% CI 9.23–13.4) prevalence of radiographically ascertained vertebral fractures in a random sample of 1,922 women from cities within five different countries. These figures are similar to findings from studies in Beijing, China, some regions of Europe, and slightly lower than those found in the USA using the same standardized methodology. Introduction  We report the first study of radiographic vertebral fractures in Latin America. Methods  An age-stratified random sample of 1,922 women aged 50 years and older from Argentina, Brazil, Colombia, Mexico, and Puerto Rico were included. In all cases a standardized questionnaire and lateral X-rays of the lumbar and thoracic spine were obtained after informed consent. Results  A standardized prevalence of 11.18 (95% CI 9.23–13.4) was found. The prevalence was similar in all five countries, increasing from 6.9% (95% CI 4.6–9.1) in women aged 50–59 years to 27.8% (95% CI 23.1–32.4) in those 80 years and older (p for trend < 0.001). Among different risk factors, self-reported height loss OR = 1.63 (95% CI: 1.18–2.25), and previous history of fracture OR = 1.52 (95% CI: 1.14–2.03) were significantly (p < 0.003 and p < 0.04 respectably) associated with the presence of radiographic vertebral fractures in the multivariate analysis. In the bivariate analyses HRT was associated with a 35% lower risk OR = 0.65 (95% CI: 0.46–0.93) and physical activity with a 27% lower risk of having a vertebral fracture OR = 0.73 (95% CI: 0.55–0.98), but were not statistically significant in multivariate analyses Conclusion  We conclude that radiographically ascertained vertebral fractures are common in Latin America. Health authorities in the region should be aware and consider implementing measures to prevent vertebral fractures.     

结直肠癌患者的DNA修复基因XRCC1单核苷酸多态研究

目的 探讨DNA碱基切除修复基因XRCC1单核苷酸多态与结直肠癌易感性的关系.方法 采用病例-对照分子流行病学方法,以聚合酶链反应-限制性酶切片段多态性(PCRRFLP)方法分析120例结直肠癌患者和150例正常对照XRCC1基因单核苷酸多态Arg194Trp和Arg399Gln的基因型分布,并比较不同基因型与结直肠癌风险的关系.结果 正常人群中194Arg/Arg、Arg/Trp和Trp/Trp基因型频率分别为52.0%、42.0%和6.0%,而结直肠癌患者中分别为40.8%、46.7%和12.5%,分布差异有统计学意义(P＜0.05,趋势检验).与携带野生基因型Arg/Arg者比较,携带Trp/Trp基因型个体患结直肠癌的风险降低了1. 43倍(校正OR=2.43;95%CI=1.10～5.92).而194Arg/Trp基因型和Arg399Gln遗传多态则与结直肠癌风险无关.结论 DNA修复基因XRCC1 Arg194Trp多态可能是结直肠癌发生的遗传易感因素.     

Risk factors for hospital-acquired urinary tract infection: a case–control study

The objective is to assess risk factors and microbiological aspects of hospital-acquired urinary tract infection (HAUTI) on six wards of a general regional hospital in Serbia. A case–control study was nested within prospective cohort HAUTIs study conducted from January 1 to December 31, 2007. Three controls were identified for each patient with HAUTI, being chronologically the next three patients surveyed who did not develop HAUTI. The patients and controls were matched by sex and age (±5 years). Assessment of 8,467 patients during the study period revealed HAUTI in 125 (116 symptomatic and 9 asymptomatic). The overall incidence rate of HAUTI was 14.8 cases/1,000 admissions. The mean age (range) of cases and controls was 64.9 (18–85) and 65.2 (17–86), respectively. Multivariate logistic regression analysis showed that duration of catheterization >5 days (OR = 51.91; 95% CI = 23.46–114.82) and the ASA score (OR = 13.42; 95% CI = 2.14–84.30) were independently associated with increased risk of HAUTIs. The most frequently isolated Gram-negative bacteria were Enterobacter, Klebsiella sp., Proteus mirabilis and Escherichia coli. Enterococcus sp. was the most frequent Gram-positive bacteria.     

Risk of Atrial Fibrillation Associated with Use of Bisphosphonates and Other Drugs Against Osteoporosis: A Cohort Study

We studied the association between bisphosphonate use and risk of atrial fibrillation or flutter and the effect of confounders such as heart and lung disease in a nationwide retrospective cohort from Denmark. All users of bisphosphonates and other drugs against osteoporosis between 1996 and 2006 (n = 103,562) were the exposed group and three age- and gender-matched controls from the general population (n = 310,683) were the nonexposed group. The main outcome measure was atrial fibrillation or atrial flutter. Before initiation of treatment against osteoporosis, no excess of atrial fibrillation or flutter was present for any drug except for etidronate (OR = 1.22, 95% CI 1.15–1.29). After initiation of treatment, raloxifene was not associated with any excess risk of atrial fibrillation (OR = 0.98, 95% CI 0.72–1.33). Etidronate (HR = 1.08, 95% CI 1.02–1.14) and alendronate (HR = 1.09, 95% CI 1.00–1.20) were associated with an excess risk of atrial fibrillation after treatment start if statistical adjustments were made for cardiovascular disease. However, this association disappeared upon statistical adjustment for chronic obstructive pulmonary disease (COPD) (etidronate HR = 1.04, 95% CI 0.98–1.10; alendronate HR = 1.05, 95% CI 0.96–1.15). In patients using etidronate (12.5% vs. 3.8%) and alendronate (11.4% vs. 4.6%) major differences were present in prevalence of COPD at start of treatment compared to matched controls. In conclusion, oral bisphosphonates do not seem to be associated with an excess risk of atrial fibrillation. Any excess risk seen in prior studies may be due to confounding from COPD.     

Clinical risk factors for osteoporotic fractures in Brazilian women and men: the Brazilian Osteoporosis Study (BRAZOS)

Summary  The Brazilian Osteoporosis Study (BRAZOS) is the first epidemiological study carried out in a representative sample of Brazilian men and women aged 40 years or older. The prevalence of fragility fractures is about 15.1% in the women and 12.8% in the men. Moreover, advanced age, sedentarism, family history of hip fracture, current smoking, recurrent falls, diabetes mellitus and poor quality of life are the main clinical risk factors associated with fragility fractures. Introduction  The Brazilian Osteoporosis Study (BRAZOS) is the first epidemiological study carried out in a representative sample of Brazilian men and women aged 40 years or older with the purpose of identifying the prevalence and the main clinical risk factors (CRF) associated with osteoporotic fracture in our population. Methods  A total of 2,420 individuals (women, 70%) from 150 different cities in the five geographic regions in Brazil, and all different socio-economical classes were selected to participate in the present survey. Anthropometrical data as well as life habits, fracture history, food intake, physical activity, falls and quality of life were determined by individual quantitative interviews. The representative sampling was based on Brazilian National data provided by the 2000 and 2003 census. Low trauma fracture was defined as that resulting of a fall from standing height or less in individuals 50 years or older at specific skeletal sites: forearm, femur, ribs, vertebra and humerus. Sampling error was 2.2% with 95% confidence intervals. Logistic regression analysis models were designed having the fragility fracture as the dependent variable and all other parameters as the independent variable. Significance level was set as p < 0.05. Results  The average of age, height and weight for men and women were 58.4 ± 12.8 and 60.1 ± 13.7 years, 1.67 ± 0.08 and 1.56 ± 0.07 m and 73.3 ± 14.7 and 64.7 ± 13.7 kg, respectively. About 15.1% of the women and 12.8% of the men reported fragility fractures. In the women, the main CRF associated with fractures were advanced age (OR = 1.6; 95% CI 1.06–2.4), family history of hip fracture (OR = 1.7; 95% CI 1.1–2.8), early menopause (OR = 1.7; 95% CI 1.02–2.9), sedentary lifestyle (OR = 1.6; 95% CI 1.02–2.7), poor quality of life (OR = 1.9; 95% CI 1.2–2.9), higher intake of phosphorus (OR = 1.9; 95% CI 1.2–2.9), diabetes mellitus (OR = 2.8; 95% CI 1.01–8.2), use of benzodiazepine drugs (OR = 2.0; 95% CI 1.1–3.6) and recurrent falls (OR = 2.4; 95% CI 1.2–5.0). In the men, the main CRF were poor quality of life (OR = 3.2; 95% CI 1.7–6.1), current smoking (OR = 3.5; 95% CI 1.28–9.77), diabetes mellitus (OR = 4.2; 95% CI 1.27–13.7) and sedentary lifestyle (OR = 6.3; 95% CI 1.1–36.1). Conclusion  Our findings suggest that CRF may contribute as an important tool to identify men and women with higher risk of osteoporotic fractures and that interventions aiming at specific risk factors (quit smoking, regular physical activity, prevention of falls) may help to manage patients to reduce their risk of fracture.     

Caspase 9 and Caspase 8 Gene Polymorphisms and Susceptibility to Bladder Cancer in North Indian Population

Background  Dysregulation of apoptosis plays a crucial role in carcinogenesis. Our aim was to investigate the association of Caspase 9 and Caspase 8 gene polymorphism with bladder cancer (BC) susceptibility. Methods  We undertook a case–control study of 212 (BC) cases and 250 controls to investigate the association between Caspase 9-1263A > G, Caspase 9-293del, and Caspase 8-6 N ins/del polymorphism and BC susceptibility by polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) method, and further to study the influence on recurrence in patients after Bacillus Calmette–Guerin (BCG) immunotherapy. Results  Overall, no statistically significant association was observed in Caspase 9-293del and Caspase 8. Nevertheless, Caspase 9-1263GG genotype was at reduced risk of BC [p = 0.010; odds ratio (OR) = 0.487]. Caspase 9-1263AG genotype was also observed to be significantly associated with reduced risk with high-risk non-muscle-invasive bladder cancer (NMIBC) (TaG_2-3, T1G_1-3) and invasive tumors (T2 +) of BC (P = 0.042, OR = 0.39 and P = 0.013, OR = 0.028 respectively). Caspase 9-293del, heterozygous (–/+) genotype, too, demonstrated protective effect in high-risk NMIBC (P = 0.017; OR = 0.205). Haplotype analysis revealed variant genotypes Caspase 9AG + GG/Caspase 8 DI + II to be at reduced risk of BC (= 0P.014, OR = 0.47). The GG genotype of Caspase 9-1263 was associated with reduced risk for recurrence in BCG-treated patients [hazard ratio (HR) = 0.217, P = 0.005], thus showing increased recurrence-free survival (log-rank P = 0.024). Conclusion  Polymorphism in Caspase 9-1263 was observed to play a protective role in susceptibility to BC risk. Caspase 9 gene variants were also associated with reduced risk of NMBIC stages. The variant G allele at Caspase 9-1263 may be responsible for increased recurrence-free survival in BCG-treated patients.     

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.     

Surgical Site Infection Following Surgery for Inflammatory Bowel Disease in Patients with Clean-Contaminated Wounds

Background  It is generally believed that the accompanying conditions in patients with inflammatory bowel disease (IBD) are associated with a high incidence of surgical site infection (SSI), and sometimes these patients are classified as compromised hosts without definitive clinical evidence. The aim of this study was to clarify the impact of IBD on the occurrence and features of SSI in patients with clean-contaminated wounds. Methods  We conducted prospective SSI surveillance of 580 patients with clean-contaminated wounds who underwent surgery between March 2006 and December 2007 using the National Nosocomial Infection Surveillance system. Multivariate analyses using stepwise logistic regression were performed to determine risk factors for SSI. Results  A total of 562 patients with clean-contaminated wounds who underwent surgery for IBD [ulcerative colitis (UC), n = 173; Crohn’s disease (CD), n = 122] or colorectal cancer [(CA), n = 267] were identified for evaluation. SSI was observed in 12.6% of all patients and there was no significant difference in infection rate by type of disease (UC, 14.5%; CD, 13.9%; CA, 10.9%). Multivariate logistic regression analysis yielded an ASA score ≥3 [odds ratio (OR) = 2.04; 95% confidence interval (CI) = 1.06–3.93] and rectal surgery (OR = 2.35; 95% CI = 1.28–4.31) as independent risk factors for SSI. IBD surgery was not an independent risk factor for overall SSI (OR = 1.62; 95% CI = 0.94–2.80). However, there was a significant difference in the incidence of incisional SSI [IBD, 11.9% (UC, 12.7%; CD, 10.7%); CA, 4.9%, p = 0.003]. In the analysis of rectal surgery, the incidence of incisional SSI was 5.3% in CA patients, 12.0% in UC patients, and 26.3% in CD patients. In contrast to overall SSI data, IBD surgery was found to be an independent risk factor for incisional SSI (OR = 2.59; 95% CI = 1.34–5.03). Conclusions  In patients of surgery restricted to clean-contaminated wounds, IBD was shown to be an independent risk factor for incisional SSI. With the use of proper operative procedures and techniques, the incidence of organ/space SSI should not be high in patients who undergo an uncomplicated IBD surgical procedure.