Abstract Both inflammation and androgens are likely to be involved in the etiology of prostate cancer. There is evidence for cross-talk between androgen and inflammation pathways, yet little is known about the joint contribution of inflammation and androgens to prostate cancer risk. Thus, we evaluated the joint effects of 9,932 tag single nucleotide polymorphisms (SNPs) in 774 inflammation-related genes and four serum androgen measures (total testosterone [T], bioavailable T, 3α-androstanediol glucuronide [3α diol G], and androstenedione) on risk of prostate cancer in 516 incident cancer cases and 560 controls from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. SNPs included in this study were genotyped as part of the National Cancer Institute Cancer Genetic Markers of Susceptibility genome-wide association study. Likelihood ratio tests (LRT) were used to compare logistic models of prostate cancer regressed on age, center, the androgen (in quartiles), the SNP (additive genetic coding) and the SNP x hormone interaction term to logistic models of prostate cancer regressed on age, center, and the androgen. False discovery rate (FDR) control was used to adjust for multiple testing. Statistically significant LRT P-values were noted for T and three intronic SNPs in linkage disequilibrium (r2>0.7) within the HIPK2 gene on 7q34 (rs10256326, rs7788362, and rs12539357; FDR-adjusted P=0.04 for all SNPs). For each SNP, the minor allele was associated with a reduced prostate cancer risk in men with serum T levels in the lower three quartiles, but was associated with an increased risk among men in the highest quartile of serum T. LRT P-values of borderline statistical significance were also seen for joint effects of these three SNPs and bioavailable T on risk of prostate cancer (FDR-adjusted P=0.07 for all SNPs). There were no significant joint effects for any of the SNPs with 3αdiol G or androstenedione after adjustment for multiple tests. Our preliminary results suggest that T levels could interact with HIPK2 gene variants to influence prostate cancer risk. HIPK2 is an attractive candidate gene for further evaluation because it codes for a serine/threonine kinase involved in transcriptional regulation, particularly involved in p53-dependent and independent regulation of cell cycle control and apoptosis. Future studies are needed to confirm our preliminary findings and to further understand the possible interaction between T and genetic variants in HIPK2, which could contribute to prostate cancer risk. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 924.
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: Compare the efficacy of infiltrated local anaesthetic agents with topically applied local anaesthetic agents for repair of dermal (skin) lacerations. We will determine anaesthetic efficacy by the patient's self‐report of pain intensity during repair of the wound. Compare the efficacy of various single or multi‐component topical anaesthetic agents for repair of dermal lacerations. Identify cocaine‐free topically applied local anaesthetics that are potentially equally efficacious to cocaine‐containing topical anaesthetics. Compare the safety of the various topically applied local anaesthetic agents or preparations
Abstract 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) were associated with measured total testosterone (P<1.1×10−3) and calculated bioavailable testosterone (P<6.3×10−4). Suggestive associations were seen for a cluster of 9 SNPs in prostate cancer risk region 1 and androstenedione (P<0.05). These preliminary findings, although in need of confirmation in larger studies, suggest that genetic variations in the 8q24 cancer risk regions may correlate with androgen levels, which in turn may provide some clues for the strong link between 8q24 and prostate cancer risk. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4732.
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.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.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 <8) and low stage (clinical stages I or II); RR = 0.75; 95% CI = 0.62-0.91). In contrast, no association was noted between diabetes and aggressive disease (i.e., high grade or high stage (Gleason sum >or=8 or clinical stages III or IV); RR = 1.04, 95% CI = 0.74-1.45). In further analyses, the association between diabetes and aggressive prostate cancer was suggestively positive for men who were lean (RR = 1.64, 95% CI = 0.87-3.07; BMI < 25 kg/m(2)) and it was positive for men who were the most physically active (RR = 1.63; 95% CI = 1.07-2.62; 3+ hours vigorous activity/week). By comparison, no relations of diabetes to aggressive prostate cancer were noted for their heavier or physically less active counterparts (p-value for tests of interaction = 0.10 and 0.03 BMI and physical activity, respectively).In this study, diabetes showed divergent relations with prostate cancer by tumor aggressiveness. Specifically, diabetes was inversely associated with early stage prostate cancer but it showed no relation with aggressive prostate cancer. Exploratory analyses suggested a positive association between diabetes and aggressive prostate cancer in the subgroup of men with a low BMI.
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.
Supplementary Table 1 from Association between Genetic Variants in the 8q24 Cancer Risk Regions and Circulating Levels of Androgens and Sex Hormone–Binding Globulin
