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Supplementary Table 1 from Association between Genetic Variants in the 8q24 Cancer Risk Regions and Circulating Levels of Androgens and Sex Hormone–Binding Globulin

Background: Genome-wide association studies have identified multiple independent regions on chromosome 8q24 that are associated with cancers of the prostate, breast, colon, and bladder.Methods: To investigate their biological basis, we examined the possible association between 164 single nucleotide polymorphisms (SNPs) in the 8q24 risk regions spanning 128,101,433-128,828,043 bp, and serum androgen (testosterone, androstenedione, 3αdiol G, and bioavailable testosterone), and sex hormone–binding globulin levels in 563 healthy, non-Hispanic, Caucasian men (55-74 years old) from a prospective cohort study (the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial). Age-adjusted linear regression models were used to determine the association between the SNPs in an additive genetic model and log-transformed biomarker levels.Results: Three adjacent SNPs centromeric to prostate cancer risk-region 2 (rs12334903, rs1456310, and rs980171) were associated with testosterone (P < 1.1 × 10−3) and bioavailable testosterone (P < 6.3 × 10−4). Suggestive associations were seen for a cluster of nine SNPs in prostate cancer risk region 1 and androstenedione (P < 0.05).Conclusions: These preliminary findings require confirmation in larger studies but raise the intriguing hypothesis that genetic variations in the 8q24 cancer risk regions might correlate with androgen levels.Impact: These results might provide some clues for the strong link between 8q24 and prostate cancer risk. Cancer Epidemiol Biomarkers Prev; 19(7); 1848–54. ©2010 AACR.

Objective:This study investigated the association of cervical human papillomavirus (HPV) infection with cumulative psychosocial risk reflecting family disadvantage, psychological distress, and unhealthy lifestyle.Methods:The sample (N = 745) comprised sexually active female adolescent patie

Background Topical local anaesthetics provide effective analgesia for patients undergoing numerous superficial procedures, including repair of dermal lacerations. The need for cocaine in topical anaesthetic formulations has been questioned because of concern about adverse effects, thus novel preparations of cocaine-free anaesthetics have been developed. This review was originally published in 2011 and has been updated in 2017. Objectives To assess whether benefits of non-invasive topical anaesthetic application occur at the expense of decreased analgesic efficacy. To compare the efficacy of various single-component or multi-component topical anaesthetic agents for repair of dermal lacerations. To determine the clinical necessity for topical application of the ester anaesthetic, cocaine. Search methods For this updated review, we searched the following databases: Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 11), Cumulative Index to Nursing and Allied Health Literature (CINAHL; 2010 to December 2016), Embase (2010 to December 2016) and MEDLINE (2010 to December 2016). We did not limit this search by language or format of publication. We contacted manufacturers, international scientific societies and researchers in the field. Weemailed selected journalsand reviewed meta-registers of ongoing trials. For the previous version of this review, we searched these databases to November 2010. Selection criteria We included randomized controlled trials (RCTs) that evaluated the efficacy and safety of topical anaesthetics for repair of dermal laceration in adult and paediatric participants. Data collection and analysis Two review authors independently assessed trial quality and extracted data. We contacted study authors for additional information when needed. We collected adverse event information from trial reports. We assessed methodological risk of bias for each included study and employed the GRADE approach to assess the overall quality of the evidence. Main results The present updated review included 25 RCTs involving 3278 participants. The small number of trials in each comparison group and the heterogeneity of outcome measures precluded quantitative analysis of data for all but one outcome: pain intensity. In two pooled studies, the mean self-reported visual analogue scale (VAS; 0 to 100 mm) score for topical prilocaine-phenylephrine (PP) was higher than the mean self-reported VAS (0 to 100 mm) score for topical tetracaine-epinephrine-cocaine (TAC) by 5.59 points (95% confidence interval (CI) 2.16 to 13.35). Most trials that compared infiltrated and topical anaesthetics were at high risk of bias, which is likely to have affected their results. Researchers found that several cocaine-free topical anaesthetics provided effective analgesic efficacy. However, data regarding the efficacy of each topical agent are based mostly on single comparisons in trials with unclear or high risk of bias. Mild, self-limited erythematous skin induration occurred in one of 1042 participants who had undergone application of TAC. Investigators reported no serious complications among any of the participants treated with cocaine-based or cocaine-free topical anaesthetics. The overall quality of the evidence according to the GRADE system is low owing to limitations in design and implementation, imprecision of results and high probability of publication bias (selective reporting of data). Additional well-designed RCTs with low risk of bias are necessary before definitive conclusions can be reached. Authors' conclusions We have found two new studies published since the last version of this review was prepared. We have added these studies to those previously included and have conducted an updated analysis, which resulted in the same review conclusions as were presented previously. Mostly descriptive analysis indicates that topical anaesthetics may offer an efficacious, non-invasive means of providing analgesia before suturing of dermal lacerations. Use of cocaine-based topical anaesthetics might be hard to justify, given the availability of other effective topical anaesthetics without cocaine. However, the overall quality of the evidence according to the GRADE system is low owing to limitations in design and implementation, imprecision of results and high probability of publication bias (selective reporting of data). Additional well-designed RCTs with low risk of bias are necessary before definitive conclusions can be reached.

BACKGROUND—Androgens and inflammation have been implicated in the etiology of several cancers, including prostate cancer. Serum androgens have been shown to correlate with markers of inflammation and expression of inflammation-related genes. METHODS—In this report, we evaluated associations between 9,932 single nucleotide polymorphisms (SNPs) marking common genetic variants in 774 inflammation-related genes and four serum androgen levels (total testosterone [T], bioavailable T [BioT]; 5α-androstane-3α, 17βdiol glucuronide [3αdiol G], and 4-Androstene-3,17-dione [androstenedione]), in 560 healthy men (median age 64 years) drawn from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Baseline serum androgens were measured by radioimmunoassay. Genotypes were determined as part of the Cancer Genetic Markers of Susceptibility Study genome-wide scan. SNP-hormone associations were evaluated using linear regression of hormones adjusted for age. Gene-based p-values were generated using an adaptive rank truncated product method. RESULTS—Suggestive associations were observed for two inflammation-related genes and circulating androgen levels (false discovery rate [FDR] q-value T in MMP2 and rs3822356T>C in CD14 (FDR q-value=0.09 for both SNPs). Other genes implicated in either SNP or gene-based tests were IK with T and BioT, PRG2 with T, and TNFSF9 with androstenedione. CONCLUSIONS—These results suggest possible cross-talk between androgen levels and inflammation pathways, but larger studies are needed to confirm these findings and to further clarify the interrelationship between inflammation and androgens and their effects on cancer risk.

Background: Genome-wide association studies have identified multiple independent regions on chromosome 8q24 that are associated with cancers of the prostate, breast, colon, and bladder. Methods: To investigate their biological basis, we examined the possible association between 164 single nucleotide polymorphisms (SNPs) in the 8q24 risk regions spanning 128,101,433-128,828,043 bp, and serum androgen (testosterone, androstenedione, 3αdiol G, and bioavailable testosterone), and sex hormone–binding globulin levels in 563 healthy, non-Hispanic, Caucasian men (55-74 years old) from a prospective cohort study (the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial). Age-adjusted linear regression models were used to determine the association between the SNPs in an additive genetic model and log-transformed biomarker levels. Results: Three adjacent SNPs centromeric to prostate cancer risk-region 2 (rs12334903, rs1456310, and rs980171) were associated with testosterone (P < 1.1 × 10−3) and bioavailable testosterone (P < 6.3 × 10−4). Suggestive associations were seen for a cluster of nine SNPs in prostate cancer risk region 1 and androstenedione (P < 0.05). Conclusions: These preliminary findings require confirmation in larger studies but raise the intriguing hypothesis that genetic variations in the 8q24 cancer risk regions might correlate with androgen levels. Impact: These results might provide some clues for the strong link between 8q24 and prostate cancer risk. Cancer Epidemiol Biomarkers Prev; 19(7); 1848–54. ©2010 AACR.

Gallstone disease is more common among overweight individuals, particularly in women. We conducted a cross-sectional case-control study of Chinese women nested in the Shanghai Women's Health Study (SWHS) to evaluate the association of gallstone disease with body mass index (BMI), waist to hip ratio (WHR), and physical activity (PA).The study included 8,485 women with self-reported, physician-diagnosed, prevalent gallstone disease and 16,970 frequency-matched controls by birth year and age at gallstone diagnosis (4-year intervals). Information on height, weight history, waist and hip circumferences, physical activities, and other exposures was obtained by in-person interview.: Usual BMI (p trend0.001) and WHR (p trend0.001) were both related to a high prevalence of gallstone disease, and a significant interaction between BMI and WHR on gallstone risk was found (odds ratio [OR] = 3.82, 95%CI [95% confidence interval] 2.47-5.23 for those with both highest BMI and WHR relative to those with lowest BMI and WHR, p interaction = 0.03). Gallstone risk was positively associated with cumulative occupational sitting time (p trend = 0.01) and inversely associated with occupational cumulative energy expenditure (p trend = 0.03) as well as with household PA (p trend = 0.02).Our findings further support that overall and central excessive adiposity is an independent risk factor for gallstones in women. In addition, regardless of adiposity level, being physically active may ameliorate the risk of this disease.

Cigarette smoking is irrefutably the strongest risk factor for lung cancer; however, approximately 25% of cases worldwide occur among nonsmokers. The age-adjusted annual incidence rate of lung cancer in Shanghai, a region where relatively few women smoke cigarettes, is one of the highest in the world. To help further elucidate the etiology of lung cancer among nonsmokers, the authors examined hormonal factors among women who were lifetime nonsmokers. They analyzed data from the prospective Shanghai Women's Health Study, which recruited Chinese women aged 40-70 years between 1996 and 2000 from selected urban communities. The current analysis included 71,314 women (n = 220 cases) who were lifetime nonsmokers and had no history of cancer at baseline. Later age at menopause (or =51 vs.46 years; hazard ratio (HR) = 0.63, 95% confidence interval (CI): 0.40, 1.00), longer reproductive period (or =36 vs.31 years; HR = 0.60, 95% CI: 0.39, 0.93), higher parity (or =4 vs. 0 children; HR = 0.42, 95% CI: 0.19, 0.90), and intrauterine device use (HR = 0.59, 95% CI: 0.41, 0.86) were associated with decreased risks of lung cancer. This large prospective study suggests a potential role for hormonal factors in the etiology of lung cancer among nonsmoking women.

Objective A history of diabetes has been fairly consistently related to a reduced prostate cancer risk, but previous investigations have not always addressed whether the relation with diabetes varies by prostate cancer aggressiveness or the association between diabetes and prostate cancer is modified by physical activity level and body mass, variables closely related to glucose metabolism. Methods We prospectively examined the diabetes–prostate cancer risk relationship among 33,088 men in the screening arm of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Results During 8.9 years follow-up, we ascertained 2,058 incident prostate cancer cases. Diabetes history was related to decreased risk of total prostate cancer (RR = 0.80, 95% CI = 0.68–0.95). The apparent protection afforded by diabetes was primarily due to the inverse relation with non-aggressive disease (i.e., the combination of low grade (Gleason sum

IGF-1 and IGFBP-3 may influence risk of prostate cancer through their roles in cellular growth, metabolism and apoptosis, however, epidemiologic results have been inconsistent. The role of obesity in prostate cancer risk is not clearly understood, but hyperinsulinemia-related increases in bioactive IGF-1 levels, associated with obesity, could be a component of the relationship between the IGF-axis and prostate cancer. We conducted a nested case-control study in the prospective Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial to examine associations between IGF-1 and IGFBP-3 and risk of prostate cancer. A total of 727 incident prostate cancer cases and 887 matched controls were selected for this analysis. There was no clear overall association between IGF-1, IGFBP-3 and IGF-1:IGFBP-3 molar ratio (IGFmr) and prostate cancer risk, however, IGFmr was associated with risk in obese men (BMI > 30, p-trend = 0.04), with a greater than 2-fold increased risk in the highest IGFmr quartile (OR 2.34, 95% CI 1.10-5.01). Risk was specifically increased for aggressive disease in obese men (OR 2.80, 95% CI 1.11-7.08). In summary, our large prospective study showed no overall association between the insulin-like growth factor axis and prostate cancer risk, however, IGFmr was related to risk for aggressive prostate cancer in obese men.

Study Objective The increasing prevalence of adolescent obesity has led to consideration of the potential effect of obesity on risky sexual behaviors. In the current study we examined whether body mass index (BMI) was related to age at sexual debut, type of sexual behavior, partner number, and condom use in a population of adolescent women at high risk for obesity and risky sexual behaviors. Design, Setting, and Participants Cross-sectional examination of 860 sexually active, predominantly minority, adolescent women who received medical care at an urban health center from 2007 through 2013. Intervention and Main Outcome Measures Self-reported age at sexual debut, types of sexual intercourse, number of partners and condom use was compared with clinically assessed BMI. Results BMI was positively associated with number of sexual partners (P = .001) and history of attempted anal intercourse (P = .002). An inverse association was observed with age at first anal intercourse (P = .040). Conclusion In this sample of adolescent women, increased BMI was associated with riskier sexual practices at a younger age. Results of this study suggest that overweight and obese adolescents are a vulnerable population who might need targeted sexual health counseling.

Many factors contribute to pain after landmine injury. In preclinical models, both tissue injury and nerve injury are able, within a few tens of minutes, to initiate a cascade of processes that may culminate in persistent pain [1–3]. Initially mechanical and thermal activation of nociceptors appear at the site of damage, and are quickly followed by inflammatory activation [1,3]. Ectopic and perhaps ephaptic activity can quickly add to the neuronal chaos [4]. These processes become the source of high-intensity, long-duration impulses and this intense nociceptive barrage leads almost immediately to changes in the dorsal horn of the spinal cord, particularly in the second-order transmission cells [5–8]. Experimental inflammation activates gene expression in the dorsal horn within 20 minutes [2]. Ligating the isolated rat sciatic nerve within hours leads to novel gene expression in the dorsal horn and to swelling and inflammation in the nerve itself [9]. In virtually every instance of landmine injury, sufficient time elapses before initial care so that the patient must be viewed as already being in a subacute phase of pain and thus is no longer suitable for “acute” or “preemptive” intervention. The concept of “preemptive” analgesia for later medical procedures, such as stump revision or re-amputation, may be applicable. Yet even then, patients already have well-established “wind-up” or “sensitization” processes that are mediated through multiple mechanisms. Because treatment with any form of analgesic is rarely begun within hours if not days after the initial trauma, virtually every mechanism recognized to generate subacute and “chronic” pain in preclinical models and clinical practice has ample time to develop in the patient. As time passes after any injury, additional sources of persistent pain may occur as a result of active pathophysiological processes (such as infection or …

Exposure to estrogens is a likely cause of endometrial cancer, but the means by which estrogens exert this effect are not entirely clear. One hypothesis is that certain estrogen metabolites bind to the DNA, forming bulky adducts that damage the DNA and initiate carcinogenesis. A woman's reduced capacity to repair such damage may increase her risk of endometrial cancer. We conducted a population-based case-control study in western Washington State to address the role of variation in nucleotide excision repair genes on the risk of endometrial cancer. Case women (n = 371), ages 50 to 69 years, were diagnosed with invasive endometrial cancer between 1994 and 1999. Control women (n = 420) were selected using random-digit dialing (ages 50-65 years) and by random selection from Health Care Financing Administration data files (ages 66-69 years). Genotyping assays were done for ERCC1, ERCC2 (XPD), ERCC4 (XPF), ERCC5 (XPG), XPA, and XPC. No appreciable differences between cases and controls were observed in the genotype distributions of ERCC1 (c8092a and c19007t), ERCC2 (D312N, K751Q, and c22541a), ERCC4 (R415Q and t30028c), or ERCC5 (D1104H). Carriage of at least one variant allele for XPA G23A was associated with decreased risk of endometrial cancer [odds ratio (OR), 0.70; 95% confidence interval (95% CI), 0.53-0.93]. Carriage of at least one XPC A499V variant allele was associated with a modest decrease in risk (OR, 0.79; 95% CI, 0.59-1.05). Women with variant alleles at both XPC A499V and K939Q had 58% of the risk of women with no XPC variant alleles (OR, 0.58; 95% CI, 0.35-0.96). Our data suggest that interindividual variation in XPA and XPC influences a woman's risk of endometrial cancer.

Study Objectives To compare the efficacy of infiltrated local anesthesia with topical anesthesia for repair of dermal laceration, to analyze the efficacy of single or multicomponent topical anesthetics, and to identify topical formulations that are potentially less costly and equally efficacious as cocaine-containing topical anesthetics. Design Systematic review of randomized controlled trials. Setting University-affiliated hospital. Patients Pediatric and adult subjects. Measurements and Main Results Twenty-two trials that randomized more than 3000 patients were identified. The majority of studies demonstrated equivalent or superior analgesic efficacy for topical formulations compared with conventional intradermal infiltration. We found that cocaine is not a mandatory component of topical anesthesia. The literature discloses no significant difference in anesthetic efficacy between topical tetracaine-epinephrine-cocaine and each of the following 6 cocaine-free formulations: lidocaine-epinephrine-tetracaine, lidocaine-epinephrine, tetracaine-phenylephrine, tetracaine-lidocaine-phenylephrine, bupivicaine-norepinephrine, or prilocaine-phenylephrine. Conclusion Topical anesthetics are an efficacious, noninvasive means of providing analgesia before suturing of dermal lacerations. The use of cocaine-containing topical anesthetics can no longer be justified in light of its high cost and potential adverse effects. We have summarized the evidence, mostly favorable, supporting the use of various non–cocaine-containing topical anesthetics.

To determine separately the effect of corticotropin-releasing hormone (CRH) on analgesia and on inflammation, rats were assigned to receive CRH 60 microg/kg, CRH 300 microg/kg, morphine 4 mg/kg, or normal saline intravenously 15 min before a burn injury. Two mesh chambers that allowed collection of fluid had been previously implanted subdermally in each rat. The skin overlying the right chamber was subject to thermal injury. The left chamber served as a control. We assessed systemic analgesia, and levels of beta-endorphin and corticosterone in plasma and in chamber fluid before, 1, 4 and 24 h after drug administration. The CRH groups exhibited longer tail flick latencies than the control group (P=0.0001) although the increase in latency was of smaller magnitude than in the morphine group. We did not observe a CRH dose response for analgesia. Plasma corticosterone levels were higher in the CRH 300 microg/kg group than in the normal saline group at 4 h (P=0.03). Levels of beta-endorphin in plasma as well as the levels of corticosterone and beta-endorphin in chambers were similar in the CRH 300 microg/kg group and in the normal saline group (all P values0.1). Thus, systemically administered CRH produces analgesia in thermal injury independent of its effect on these two markers of local or systemic inflammation.

We thank Dr Poullis for his careful review of our article,1 and we are pleased to respond to the issues he has raised. First, our study was confined to patients who underwent isolated coronary artery bypass grafting. However, as in most real-world populations of patients who undergo this procedure, some of those in our study did have mild coexisting valve disease that was not felt to require concomitant repair or replacement. There were even a very few patients with more severe valve disease who, for what were likely to have been unusual circumstances, only had coronary artery bypass grafting. The increased hazard ratios associated with coexisting moderate to severe valvular insufficiency and with progressive aortic stenosis convey an important message that would not have been apparent had we excluded all such patients from our study. The presence of uncorrected, significant coexisting valve disease is associated with an increased risk of long-term …

Questions persist concerning the comparative effectiveness of percutaneous coronary intervention (PCI) and coronary-artery bypass grafting (CABG). The American College of Cardiology Foundation (ACCF) and the Society of Thoracic Surgeons (STS) collaborated to compare the rates of long-term survival after PCI and CABG.We linked the ACCF National Cardiovascular Data Registry and the STS Adult Cardiac Surgery Database to claims data from the Centers for Medicare and Medicaid Services for the years 2004 through 2008. Outcomes were compared with the use of propensity scores and inverse-probability-weighting adjustment to reduce treatment-selection bias.Among patients 65 years of age or older who had two-vessel or three-vessel coronary artery disease without acute myocardial infarction, 86,244 underwent CABG and 103,549 underwent PCI. The median follow-up period was 2.67 years. At 1 year, there was no significant difference in adjusted mortality between the groups (6.24% in the CABG group as compared with 6.55% in the PCI group; risk ratio, 0.95; 95% confidence interval [CI], 0.90 to 1.00). At 4 years, there was lower mortality with CABG than with PCI (16.4% vs. 20.8%; risk ratio, 0.79; 95% CI, 0.76 to 0.82). Similar results were noted in multiple subgroups and with the use of several different analytic methods. Residual confounding was assessed by means of a sensitivity analysis.In this observational study, we found that, among older patients with multivessel coronary disease that did not require emergency treatment, there was a long-term survival advantage among patients who underwent CABG as compared with patients who underwent PCI. (Funded by the National Heart, Lung, and Blood Institute.).

Background— Most survival prediction models for coronary artery bypass grafting surgery are limited to in-hospital or 30-day end points. We estimate a long-term survival model using data from the Society of Thoracic Surgeons Adult Cardiac Surgery Database and Centers for Medicare and Medicaid Services. Methods and Results— The final study cohort included 348 341 isolated coronary artery bypass grafting patients aged ≥65 years, discharged between January 1, 2002, and December 31, 2007, from 917 Society of Thoracic Surgeons–participating hospitals, randomly divided into training (n=174 506) and validation (n=173 835) samples. Through linkage with Centers for Medicare and Medicaid Services claims data, we ascertained vital status from date of surgery through December 31, 2008 (1- to 6-year follow-up). Because the proportional hazards assumption was violated, we fit 4 Cox regression models conditional on being alive at the beginning of the following intervals: 0 to 30 days, 31 to 180 days, 181 days to 2 years, and >2 years. Kaplan-Meier–estimated mortality was 3.2% at 30 days, 6.4% at 180 days, 8.1% at 1 year, and 23.3% at 3 years of follow-up. Harrell's C statistic for predicting overall survival time was 0.732. Some risk factors (eg, emergency status, shock, reoperation) were strong predictors of short-term outcome but, for early survivors, became nonsignificant within 2 years. The adverse impact of some other risk factors (eg, dialysis-dependent renal failure, insulin-dependent diabetes mellitus) continued to increase. Conclusions— Using clinical registry data and longitudinal claims data, we developed a long-term survival prediction model for isolated coronary artery bypass grafting. This provides valuable information for shared decision making, comparative effectiveness research, quality improvement, and provider profiling.

Background— The purpose of this study was to develop a long-term model to predict mortality after percutaneous coronary intervention in both patients with ST-segment elevation myocardial infarction and those with more stable coronary disease. Methods and Results— The American College of Cardiology Foundation CathPCI Registry data were linked to the Centers for Medicare and Medicaid Services 100% denominator file by probabilistic matching. Preprocedure demographic and clinical variables from the CathPCI Registry were used to predict the probability of death over 3 years as recorded in the Centers for Medicare and Medicaid Services database. Between 2004 and 2007, 343 466 patients (66%) of 518 195 patients aged ≥65 years undergoing first percutaneous coronary intervention in the CathPCI Registry were successfully linked to Centers for Medicare and Medicaid Services data. This study population was randomly divided into 60% derivation and 40% validation cohorts. Median follow-up was 15 months, with mortality of 3.0% at 30 days and 8.7%, 13.4%, and 18.7% at 1, 2, and 3 years, respectively. Twenty-four characteristics related to demographics, clinical comorbidity, prior history of disease, and indices of disease severity and acuity were identified as being associated with mortality. The C indices in the validation cohorts for patients with and without ST-segment elevation myocardial infarction were 0.79 and 0.78. The model calibrated well across a wide range of predicted probabilities. Conclusions— On the basis of the large and nationally representative CathPCI Registry, we have developed a model that has excellent discrimination, calibration, and validation to predict survival up to 3 years after percutaneous coronary intervention.

Sex steroid hormones influence prostate development and maintenance through their roles in prostate cellular proliferation, differentiation and apoptosis. Although suspected to be involved in prostate carcinogenesis, an association between circulating androgens and prostate cancer has not been clearly established in epidemiologic studies. We conducted a nested case-control study with prospectively collected samples in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, to examine associations of prostate cancer with androstenedione (Delta4-A), testosterone (T), sex hormone-binding globulin (SHBG) and 3alpha-androstanediol glucuronide (3alpha-diolG). A total of 727 incident Caucasian prostate cancer cases (age >/= 65 years, N = 396) and 889 matched controls were selected for this analysis. Overall, prostate cancer risks were unrelated to serum T, estimated free and bioavailable T, and SHBG; however, risks increased with increasing T:SHBG ratio (p(trend) = 0.01), mostly related to risk in older men (>/=65 years, p(trend) = 0.001), particularly for aggressive disease [highest versus lowest quartile: odds ratio (OR) 2.76, 95% confidence interval (CI) 1.50-5.09]. No clear patterns were noted for Delta4-A and 3alpha-diolG. In summary, our large prospective study did not show convincing evidence of a relationship between serum sex hormones and prostate cancer. T:SHBG ratio was related to risk in this older population of men, but the significance of this ratio in steroidal biology is unclear. (c) 2008 Wiley-Liss, Inc.

There is a wide range of aggressiveness of endometrial tumors, some being indolent and easily treated while others metastasize and prove fatal. The authors used data from three population-based, case-control studies to determine if etiologic factors differ for aggressive disease. Interview data were obtained from 1,304 female residents of western Washington State who were 45-74 years of age and diagnosed with endometrial cancer during 1985-1991, 1994-1995, and 1997-1999 and from 1,779 controls who were of similar ages and selected primarily by random digit dialing. As a means of gauging aggressiveness, tumor characteristics were abstracted from the population-based cancer registry that serves western Washington State. The risk of endometrial cancer among long-term users (> or = 8 years) of unopposed estrogens was particularly high for the least aggressive tumors (odds ratio = 18.6, 95% confidence interval: 12.2, 28.6) but was elevated for moderate and highly aggressive tumors as well (odds ratios = 6.6 and 7.1, respectively). Women who were obese, had a history of diabetes, and had fewer than two children were also at increased risk, regardless of tumor aggressiveness, while oral contraceptive users were at decreased risk of only relatively more aggressive disease. In general, a woman's risk of endometrial cancer appears to be influenced by similar risk factors regardless of disease severity.

Study objective We compare the analgesic efficacy of topical anesthetics for dermal instrumentation with conventional infiltrated local anesthesia and also compare topically available amide and ester agents with a eutectic mixture of local anesthetics (EMLA). Methods We conducted a systematic review of randomized, controlled trials. Relevant literature was identified through searches of MEDLINE, Cochrane Central Register of Controlled Trials, and the Excerpta Medica Database Drugs and Pharmacology. We limited the type of procedures to puncture of intact skin with a needle. The primary outcome was analgesic efficacy, reflected in the patient's self-report of pain intensity during dermal instrumentation. Where possible, quantitative methods were used to summarize the results. Results We identified 25 randomized controlled trials including 2,096 subjects. The results of the trials comparing the efficacy of EMLA with infiltrated local anesthetic were inconsistent. Qualitative analysis demonstrated comparable analgesic efficacy between liposome-encapsulated lidocaine and EMLA. The weighted mean difference in 100-mm visual analogue scale pain scores favored topical tetracaine over EMLA (−8.1 mm; 95% confidence interval −15.6 mm to −0.6 mm). Liposome-encapsulated tetracaine provided greater analgesia than EMLA according to the weighted mean difference in 100-mm visual analogue scale scores (−10.9 mm; 95% confidence interval −15.9 mm to −5.9 mm). Conclusion EMLA may be an effective, noninvasive means of analgesia before dermal procedures. However, we identified 3 topical anesthetics that are at least as efficacious as EMLA: tetracaine, liposome-encapsulated tetracaine, and liposome-encapsulated lidocaine. Liposomal lidocaine is commercially available in the United States and offers a more rapid onset and less expensive alternative to EMLA.

The gene encoding human 8-oxoguanine glycosylase 1 (hOGG1) is involved in DNA base excision repair. The encoded DNA glycosylase excises 7,8-dihydro-8-oxoguanine (8-OHdG), a highly mutagenic base produced in DNA as a result of exposure to reactive oxygen species (ROS). Polymorphisms in this gene may alter glycosylase function and an individual's ability to repair damaged DNA, possibly resulting in genetic instability that can foster carcinogenesis. In order to elucidate the possible impact of polymorphisms in hOGG1, we performed a literature review of both functional and epidemiologic studies that assessed the effects of these polymorphisms on repair function, levels of oxidative DNA damage, or associations with cancer risk. Fourteen functional studies and 19 epidemiologic studies of breast, colon, esophageal, head and neck, lung, nasopharyngeal, orolaryngeal, prostate, squamous cell carcinoma of the head and neck (SCCHN), and stomach cancers were identified. Although the larger functional studies suggest reduced repair function with variant alleles in hOGG1, the evidence is generally inconclusive. There is some epidemiologic evidence that risk for esophageal, lung, nasopharyngeal, orolaryngeal, and prostate is related to hOGG1 genotype, whereas risk of breast cancer does not appear related. In studies that explored potential interactions with environmental factors, cancer risk for hOGG1 genotypes differed depending on exposure, especially for colon cancer. In summary, there is limited evidence that polymorphisms in hOGG1 affect repair function and carcinogenesis. Larger, well-designed functional and epidemiologic studies are needed to clarify these relationships, especially with respect to interactions with other DNA repair enzymes and interactions with environmental factors that increase carcinogenic load.

We compared pain intensity, analgesic consumption, patient satisfaction, and length of stay in 114 patients undergoing gastric bypass surgery under general anesthesia. Patients were randomized to incisional local anesthetic infiltration plus postoperative patient-controlled analgesia (Group A), epidural anesthesia and analgesia (Group B), or postoperative patient-controlled analgesia (Group C). All received perioperative nonsteroidal antiinflammatory drugs. Age, sex, body mass index, length of stay, and patient satisfaction were equivalent in all groups. Pain at time 0 and 36 h was the smallest in Group B, greater in Group A, and greatest in Group C. Pain scores in a subset of Group A were lower at all times than in Groups B and C, but this difference was significant only at 0, 12, and 36 h. In responders, infiltration analgesia as part of a multimodal regimen offers a simple, safe, and inexpensive alternative to epidural pain control.

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Multiple genome-wide association studies have identified several independent non-coding regions in chromosome 8q24 associated with risk for cancers of the prostate, breast, colon, and bladder. To explore their biological basis, we investigated the possible association between 164 single nucleotide polymorphism (SNPs) in the 8q24 risk regions, spanning 128,101,433-128,828,043 bp, and serum androgen (testosterone, androstenedione, and 3αdiol G) and sex hormone-binding globulin levels in 563 healthy, non-Hispanic, Caucasian men (55-74 years old) from a prospective cohort study, the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Age-adjusted linear regression using SNPs in an additive genetic model showed that three adjacent SNPs centromeric to prostate cancer risk region 2 (rs12334903, rs1456310, and [rs980171][1]) were associated with measured total testosterone (P

Corrigendum to ‘‘Corticotropin-releasing hormone (CRH) produces analgesia in a thermal injury model independent of its effect on systemic beta-endorphin and corticosterone’’ [Regul. Pept. 118 (2004) 39–43] M. Soledad Cepeda, Iwona Bonney*, Jocelyn M. Weiss, Jairo Moyano, Daniel B. Carr Department of Anesthesia, San Ignacio Hospital, Javeriana University School of Medicine, Bogota, Colombia Departments of Anesthesia and Medicine, Tufts-New England Medical Center, Box #298, 750 Washington Street, Boston, MA 02111, USA