bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations between Silicone Skin Cast Score, Cumulative Sun Exposure, and Other Factors in the Ausimmune Study: A Multicenter Australian Study
Authors: Lucas Robyn M. , Ponsonby Anne-Louise , Dear Keith , Taylor Bruce V. , Dwyer Terence , McMichael Anthony J. , Valery Patricia , van der Mei Ingrid , Williams David , Pender Michael P. , Chapman Caron , Coulthard Alan , Kilpatrick Trevor
Published: November 2009

Past sun exposure is linked to a wide range of disease outcomes but is difficult to measure accurately. Silicone skin casts measure skin damage, but some studies show that age rather than sun exposure is the most important determinant of cast score. We examined skin damage scores from silicone casts of the back of the hand in a large adult sample (n = 534) with a broad range of past cumulative UV radiation (UVR) doses. Participants were ages 18 to 61 years and resided in one of four locations down the eastern Australian seaboard, spanning 27-43°S. Data were collected by questionnaire and during a nurse-led interview and examination. Silicone casts were graded from 1 to 6, where higher score represents greater damage. Higher skin damage score was associated with lighter skin pigmentation [adjusted odds ratio (AOR), 4.51; 95% confidence interval (95% CI), 2.33-8.75], fairer natural hair color, particularly red hair (AOR, 11.31; 95% CI, 4.08-31.36), and blue/gray eyes (AOR, 1.72; 95% CI, 1.14-2.59). Higher cumulative UVR dose, particularly before age 18 years, was associated with higher skin damage score (AOR, 2.06; 95% CI, 1.15-2.67 per 1,000 KJ/m2), as was number of sunburns, even after adjustment for cumulative UVR dose (AOR, 2.86; 95% CI, 1.50-5.43 for >10 sunburns ever compared with no sunburns ever). Silicone casts of the dorsum of the hand provide a measure of cumulative UVR dose and number of sunburns over the lifetime, which persists after adjustment for chronological age. They can be used as an objective measure of cumulative past sun exposure in epidemiologic studies, but other determinants of skin damage, such as skin pigmentation, should be concurrently evaluated. (Cancer Epidemiol Biomarkers Prev 2009;18(11):2887–94)
Genetic Variants of Methyl Metabolizing Enzymes and Epigenetic Regulators: Associations with Promoter CpG Island Hypermethylation in Colorectal Cancer
Authors: de Vogel Stefan , Wouters Kim A.D. , Gottschalk Ralph W.H. , van Schooten Frederik J. , de Goeij Anton F.P.M. , de Bruïne Adriaan P. , Goldbohm Royle A. , van den Brandt Piet A. , Weijenberg Matty P. , van Engeland Manon
Published: November 2009

Aberrant DNA methylation affects carcinogenesis of colorectal cancer. Folate metabolizing enzymes may influence the bioavailability of methyl groups, whereas DNA and histone methyltransferases are involved in epigenetic regulation of gene expression. We studied associations of genetic variants of folate metabolizing enzymes (MTHFR, MTR, and MTRR), DNA methyltransferase DNMT3b, and histone methyltransferases (EHMT1, EHMT2, and PRDM2), with colorectal cancers, with or without the CpG island methylator phenotype (CIMP), MLH1 hypermethylation, or microsatellite instability. Incidence rate ratios were calculated in case-cohort analyses, with common homozygotes as reference, among 659 cases and 1,736 subcohort members of the Netherlands Cohort Study on diet and cancer (n = 120,852). Men with the MTHFR 677TT genotype were at decreased colorectal cancer risk (incidence rate ratio, 0.49; P = 0.01), but the T allele was associated with increased risk in women (incidence rate ratio, 1.39; P = 0.02). The MTR 2756GG genotype was associated with increased colorectal cancer risk (incidence rate ratio, 1.58; P = 0.04), and inverse associations were observed among women carrying DNMT3b C→T (rs406193; incidence rate ratio, 0.72; P = 0.04) or EHMT2 G→A (rs535586; incidence rate ratio, 0.76; P = 0.05) polymorphisms. Although significantly correlated (P < 0.001), only 41.5% and 33.3% of CIMP tumors harbored MLH1 hypermethylation or microsatellite instability, respectively. We observed inverse associations between MTR A2756G and CIMP among men (incidence rate ratio, 0.58; P = 0.04), and between MTRR A66G and MLH1 hypermethylation among women (incidence rate ratio, 0.55; P = 0.02). In conclusion, MTHFR, MTR, DNMT3b, and EHMT2 polymorphisms are associated with colorectal cancer, and rare variants of MTR and MTRR may reduce promoter hypermethylation. The incomplete overlap between CIMP, MLH1 hypermethylation, and microsatellite instability indicates that these related “methylation phenotypes” may not be similar and should be investigated separately. (Cancer Epidemiol Biomarkers Prev 2009;18(11):3086–96)
Telomere Length in Peripheral Leukocyte DNA and Gastric Cancer Risk
Authors: Hou Lifang , Savage Sharon A. , Blaser Martin J. , Perez-Perez Guillermo , Hoxha Mirjam , Dioni Laura , Pegoraro Valeria , Dong Linda M. , Zatonski Witold , Lissowska Jolanta , Chow Wong-Ho , Baccarelli Andrea
Published: November 2009

Telomere length reflects lifetime cumulative oxidative stress from environmental exposures, such as cigarette smoking and chronic inflammation. Shortened telomere length is thought to cause genomic instability and has been associated with several cancers. We examined the association of telomere length in peripheral leukocyte DNA with gastric cancer risk as well as potential confounding factors and risk modifiers for telomere length–related risk. In a population-based study of gastric cancer conducted in a high-risk population in Warsaw, Poland, between 1994 and 1996, we measured relative telomere length in 300 cases and 416 age- and gender-matched controls using quantitative real-time PCR. Among controls, telomeres were significantly shorter in association with aging (P < 0.001), increasing pack-years of cigarette smoking (P = 0.02), decreasing fruit intake (P = 0.04), and Helicobacter pylori positivity (P = 0.03). Gastric cancer cases had significantly shorter telomere length (mean ± SD relative telomere length, 1.25 ± 0.34) than controls (1.34 ± 0.35; P = 0.0008). Gastric cancer risk doubled [odds ratio (OR), 2.04; 95% confidence interval (95% CI), 1.33-3.13] among subjects in the shortest compared with the highest quartile of telomere length (Ptrend < 0.001). Telomere length–associated risks were higher among individuals with the lowest risk profile, those H. pylori–negative (OR, 5.45; 95% CI, 2.10-14.1), nonsmokers (OR, 3.07; 95% CI, 1.71-5.51), and individuals with high intake of fruits (OR, 2.43; 95% CI, 1.46-4.05) or vegetables (OR, 2.39; 95% CI, 1.51-3.81). Our results suggest that telomere length in peripheral leukocyte DNA was associated with H. pylori positivity, cigarette smoking, and dietary fruit intake. Shortened telomeres increased gastric cancer risk in this high-risk Polish population. (Cancer Epidemiol Biomarkers Prev 2009;18(11):3103–9)
A Local Area Analysis of Racial, Ethnic, and Neighborhood Disparities in Breast Cancer Staging
Authors: Echeverría Sandra E. , Borrell Luisa N. , Brown Diane , Rhoads George
Published: November 2009

Few studies have examined the role of neighborhood socioeconomic condition in shaping breast cancer disparities in defined local areas. We tested associations between three measures of neighborhood socioeconomic condition (poverty, median income, and a composite neighborhood score) on breast cancer staging in two urban counties of the state of New Jersey. Data for these counties were obtained from the New Jersey Surveillance, Epidemiology, and End Results tumor registry and were selected because of their large racial/ethnic and socioeconomic diversity and pilot prevention efforts taking place in these areas. Our study population included Black, Latina, and White women (N = 4,589) diagnosed with breast cancer from 1999 to 2004. Each cancer case was geocoded and linked to socioeconomic data obtained from the 2000 U.S. census. Census tracts served as proxies for neighborhoods. Logistic regression models accounting for clustering of individuals within neighborhoods were fitted with Generalized Estimating Equations. Women living in neighborhoods with lower versus higher neighborhood scores were significantly more likely to have advanced-stage disease (odds ratio, 1.6; confidence intervals, 1.1-2.3), after adjusting for age at diagnosis and race/ethnicity. In analyses stratified by race/ethnicity, results remained significant for all neighborhood measures for White and Black women, but not for Latinas. Moreover, neighborhood poverty showed a weaker socioeconomic gradient in breast cancer staging among White women. Our study findings support the use of a multidimensional neighborhood index to better capture differences in cancer staging risk across racial/ethnic groups and provides evidence that population-based cancer data could be used to identify local needs specific to local populations. (Cancer Epidemiol Biomarkers Prev 2009;18(11):3024–9)
Sequence Variant on 3q28 and Urinary Bladder Cancer Risk: Findings from the Los Angeles-Shanghai Bladder Case-Control Study
Authors: Stern Mariana C. , Van Den Berg David , Yuan Jian-Min , Conti David V. , Gago-Dominguez Manuela , Pike Malcolm C. , Xiang Yong-Bing , Gao Yu-Tang , Cortessis Victoria K.
Published: November 2009

Recently, the first genome-wide association study of bladder cancer identified an association of genome-wide significance between single nucleotide polymorphism (SNP) rs715021 and urinary bladder cancer risk among European individuals. This SNP is in a haplotype block in linkage disequilibrium with the TP63 gene. We investigated the role of this SNP among 1,042 cases and 1,123 controls among non-Latino whites in Los Angeles County, CA and among Chinese in Shanghai, China. We confirmed an association between the A allele and bladder cancer risk [log-additive per A allele odds ratios (OR), 1.24; and 95% confidence intervals (95% CI), 1.02-1.52; P = 0.032] in Los Angeles County and a similar association in Shanghai (log-additive per A allele OR, 1.21; 95% CI, 0.98-1.49; P = 0.080). These estimates did not differ by study site, smoking status, or gender. However, the effects were greater in older individuals. Analysis within non-Latino whites, for whom we had histologic results, revealed that this association was restricted to low-risk tumors (OR, 1.49; 95% CI, 1.17-1.92; P = 0.002) and absent among high-risk tumors (OR, 1.03; 95% CI, 0.80-1.33; P = 0.790; heterogeneity, P = 0.019). A positive association (OR, 1.56; 95% CI, 0.93-2.62; P = 0.089) was only observed among high-risk tumors from individuals older than 56 years old (interaction, P = 0.045). Our results suggest that a TP63 gene variant may increase susceptibility for the development of urinary bladder tumors with low risk of progression. (Cancer Epidemiol Biomarkers Prev 2009;18(11):3057–61)
Genetic Variants in the Vitamin D Receptor Are Associated with Advanced Prostate Cancer at Diagnosis: Findings from the Prostate Testing for Cancer and Treatment Study and a Systematic Review
Authors: Chen Lina , Davey Smith George , Evans David M. , Cox Angela , Lawlor Debbie A. , Donovan Jenny , Yuan Wei , Day Ian N. M. , Martin Richard M. , Lane Athene , Rodriguez Santi , Davis Michael , Zuccolo Luisa , Collin Simon M. , Hamdy Freddie , Neal David , Lewis Sarah J.
Published: November 2009

Low levels of plasma vitamin D have been implicated as a possible risk factor for both prostate cancer incidence and advanced disease, and recent phase II trials suggest that vitamin D supplementation might delay progression of prostate cancer. Common polymorphisms in the vitamin D receptor (VDR) are associated with VDR activity and are therefore potentially useful proxies for assessing whether vitamin D is causally related to advanced prostate cancer. We genotyped five well-known VDR polymorphisms in 1,604 men with prostate cancer from the Prostate Testing for Cancer and Treatment study. Our aim was to examine the association between VDR polymorphisms and cancer stage (localized versus advanced) as well as cancer grade (Gleason score <7 versus ≥7). Moreover, we also carried out a systematic review and meta-analysis of 13 similar studies. As a result of our meta-analysis, we revealed three polymorphisms, BsmI, ApaI, and TaqI, associated with high Gleason score with an overall summary odds ratios (95% confidence intervals) of 1.12 (1.00-1.25; bb versus BB + Bb), 1.25 (1.02-1.53; aa versus AA + Aa), and 0.82 (0.69-0.98; Tt + tt versus TT), respectively. The haplotype analysis revealed that the BsmI (B)-ApaI (A)-TaqI (t) participants compared with BsmI (b)-ApaI (a)-TaqI (T) individuals were less likely to have high Gleason scores (odds ratio, 0.84; 95% confidence interval, 0.71-1.00; Punadjusted = 0.050; Padjusted = 0.014). Our finding provides some support for the hypothesis that low levels of vitamin D may increase the risk of prostate cancer progression. (Cancer Epidemiol Biomarkers Prev 2009;18(11):2874–81)
Elevated Cancer Mortality in the Relatives of Patients with Pancreatic Cancer
Authors: Wang Li , Brune Kieran A. , Visvanathan Kala , Laheru Daniel , Herman Joseph , Wolfgang Christoper , Schulick Richard , Cameron John L. , Goggins Michael , Hruban Ralph H. , Klein Alison P.
Published: November 2009

Most inherited cancer syndromes are characterized by the familial clustering of cancers at several organ sites. To determine if cancers, other than pancreatic cancer, cluster in pancreatic cancer kindreds, we examined mortality patterns among the relatives of National Familial Pancreatic Tumor Registry probands. Over 200,000 person-years of follow-up from 8,564 first-degree relatives of probands and 1,007 spouse controls were included in these analyses. We compared mortality rates of National Familial Pancreatic Tumor Registry participants to US population rates using weighed standardized mortality ratios (wSMR). Analyses were stratified by family history of pancreatic cancer (sporadic versus familial), family history of young onset pancreatic cancer (<50 years), and family history score. Cancer mortality was increased in both the relatives of sporadic probands [wSMR 1.55, 95% confidence interval (95% CI) 1.39-1.73] and familial probands (wSMR 1.41, 95% CI 1.26-1.58). Relatives of familial probands had a significantly increased risk of dying from breast (wSMR 1.66, 95% CI 1.15-2.34), ovarian (wSMR 2.05, 95% CI 1.10-3.49), and bile duct cancers (wSMR 2.89, 95% CI 1.04-6.39). Relatives of sporadic probands were at increased risk of dying from bile duct cancer (wSMR 3.01, 95% CI 1.09-6.67). Relatives of young onset probands were at higher risk of dying from cancers of the breast (wSMR 1.98, 95% CI 1.01-3.52), colon (wSMR 2.31, 95% CI 1.30-3.81) and prostate (wSMR 2.31, 95% CI 1.14-4.20). Increased cancer mortality was not observed in the spouse controls. Our results show that relatives of pancreatic cancer patients are at higher risk of developing cancers at other sites and highlight the importance of complete family history in clinical risk assessment. (Cancer Epidemiol Biomarkers Prev 2009;18(11):2829–34)
Enrichment of Low Penetrance Susceptibility Loci in a Dutch Familial Colorectal Cancer Cohort
Authors: Middeldorp Anneke , Jagmohan-Changur Shantie , van Eijk Ronald , Tops Carli , Devilee Peter , Vasen Hans F. A. , Hes Frederik J. , Houlston Richard , Tomlinson Ian , Houwing-Duistermaat Jeanine J. , Wijnen Juul T. , Morreau Hans , van Wezel Tom
Published: November 2009

Recent genome-wide association studies have identified several loci that confer an increased risk of colorectal cancer (CRC). We studied the role of the 8q24.21 (rs6983267), 18q21.1 (rs12953717), 15q13.3 (rs4779584), 11q23.1 (rs3802842), 8q23.3 (rs16892766), and 10p14 (rs10795668) risk variants in a series of 995 Dutch CRC cases and 1340 controls. The CRC cases were selected on basis of having a family history of CRC and/or early-onset disease. The detailed clinical and molecular data available on the cases allowed us to examine the relationship between risk variants and clinicopathologic characteristics. We replicated the association with an increased risk of CRC cancer for all loci, except 10p14. The association with the variant on chromosome 15q13.3 was confirmed for the first time. The risks associated with variants in our series were higher (not significant) than those previously reported, consistent with our series reflecting genetic enrichment. Moreover, we show that familial CRC cases possess an increased number of risk alleles compared with solitary CRC cases (early-onset; mean age at diagnosis of 48.5 years). We also identified a significant increase in the number of risk alleles in families with early-onset disease (≤50 years) compared with late-onset families (>50 years). In solitary CRC patients, enrichment for risk alleles was not observed, suggesting that other causes of increased CRC risk play a role in these cases. Overall, our results suggest that clustering of low-risk variants may explain part of the excess risk in CRC families. (Cancer Epidemiol Biomarkers Prev 2009;18(11):3062–7)
DNA Hypermethylation ofESR1andPGRin Breast Cancer: Pathologic and Epidemiologic Associations
Authors: Gaudet Mia M. , Campan Mihaela , Figueroa Jonine D. , Yang Xiaohong R. , Lissowska Jolanta , Peplonska Beata , Brinton Louise A. , Rimm David L. , Laird Peter W. , Garcia-Closas Montserrat , Sherman Mark E.
Published: November 2009

Improved understanding of the etiology of estrogen receptor-α (ERα)–negative and progesterone receptor (PR)–negative breast cancers may permit improved risk prediction. In vitro studies implicate DNA hypermethylation of the ERα and PR promoters in the pathogenesis of ERα-negative and PR-negative tumors, but results are not definitive. We evaluated 200 invasive breast cancers selected from a population-based case-control study. DNA extracted from fixed tumor tissue cores was tested using MethyLight to assess DNA methylation at four CpG islands: ESR1 promoters A and B; PGR promoters A and B; and a CpG shore, ESR1 promoter C. DNA methylation results were compared with levels of ERα and PR, tumor characteristics, and breast cancer risk factors. We observed mild to moderate DNA methylation levels in most tumors for ESR1 promoters A and B and PGR promoter B, and a few tumors showed mild methylation in PGR promoter A. In contrast, ESR1 promoter C showed a wide range of methylation and was weakly correlated with lower expression levels of ERα (β = −0.26; P < 0.0001) and PR (β = −0.25; P < 0.0001). The percentage of tumors with methylated PGR promoters A and B was significantly higher for tumors with low ERα (A, Fisher's test P = 0.0001; B, P = 0.033) and PR levels (A, P = 0.0006; B, P = 0.001). Our data suggest that the relationships between DNA methylation of ESR1 and PGR promoters and protein expression are weak and unlikely to represent a predominant mechanism of receptor silencing. In contrast to CpG islands, ESR1 promoter C showed a wider range of methylation levels and inverse associations with ERα and PR expression. (Cancer Epidemiol Biomarkers Prev 2009;18(11):3036–43)
Urinary Prostaglandin E2 Metabolite and Gastric Cancer Risk in the Shanghai Women's Health Study
Authors: Dong Linda M. , Shu Xiao-Ou , Gao Yu-Tang , Milne Ginger , Ji Bu-Tian , Yang Gong , Li Hong-Lan , Rothman Nathaniel , Zheng Wei , Chow Wong-Ho , Abnet Christian C.
Published: November 2009

Chronic inflammation has been implicated in the etiology of gastric cancer. Prostaglandin E2 (PGE2) is one of the major end-products of the cyclooxygenase-2 pathway, an enzyme that is an important mediator of inflammation. Using a novel method of quantifying the primary urinary metabolite of PGE2 (PGE-M; 11α-hydroxy-9,15-dioxo-2,3,4,5-tetranorprostane-1,20-dioic acid), we evaluated urinary PGE-M concentrations in association with subsequent risk of development of gastric cancer in the Shanghai Women's Health Study, a large population-based prospective cohort, using a nested case-control study design. Controls were matched (1:1) to 153 gastric cancer cases by menopausal status; age, time, and date of sample collection; time interval since last meal; and availability of urine sample. Odds ratios (95% confidence intervals) were calculated using conditional logistic regression adjusted for potential confounders. Baseline urinary PGE-M levels were slightly higher among gastric cancer cases with a median of 6.4 ng/mg creatinine (interquartile range, 3.4-11.2) compared with 5.4 ng/mg creatinine among controls (interquartile range, 2.8-9.0), but this difference was not statistically significant (P = 0.34, Wilcoxon). With increasing quartiles of urinary PGE-M levels, the odds ratios (95% confidence intervals) for risk of gastric cancer increased in quartiles 2 to 4: 1.00 (0.48-2.08), 1.40 (0.67-2.91), and 1.98 (0.95-4.13), with a statistically significant test for trend (P = 0.04). The association persisted after additional adjustment for Helicobacter pylori status and was slightly strengthened among non–nonsteroidal anti-inflammatory drug users, subjects with positive H. pylori status, and for cases diagnosed within 46 months after study enrollment. Our findings suggest that higher levels of urinary PGE-M, a marker of inflammation, may be associated with gastric cancer risk. (Cancer Epidemiol Biomarkers Prev 2009;18(11):3075–8)
Modulation of Human Serum Glutathione S-Transferase A1/2 Concentration by Cruciferous Vegetables in a Controlled Feeding Study Is Influenced by GSTM1 and GSTT1 Genotypes
Authors: Navarro Sandi L. , Chang Jyh-Lurn , Peterson Sabrina , Chen Chu , King Irena B. , Schwarz Yvonne , Li Shuying S. , Li Lin , Potter John D. , Lampe Johanna W.
Published: November 2009

Glutathione S-transferases (GST) detoxify a wide range of carcinogens. Isothiocyanates (ITC), from cruciferous vegetables, are substrates for and inducers of GST. GST variants may alter ITC clearance such that response to crucifers varies by genotype. In a randomized cross-over trial, we tested the hypothesis that changes in serum GSTA1/2 concentration in response to cruciferous vegetable feeding depends on GSTM1/GSTT1 genotype. Thirty-three men and 34 women (age 20-40 years) ate four 14-day controlled diets—basal (vegetable-free), basal supplemented with two different doses of crucifers (“single dose” and “double dose”), and single-dose cruciferous-plus-apiaceous vegetables—fed per kilogram of body weight. Fasting bloods from days 0, 7, 11, and 14 of each diet period were analyzed for serum GSTA1/2 by ELISA. GSTA1/2 increased with single- and double-dose cruciferous compared with basal diet (10% and 13%, respectively; P = 0.02 and 0.004), but cruciferous-plus-apiaceous did not differ from basal (P = 0.59). Overall, GSTA1/2 was higher in GSTM1-null/GSTT1-null than GSTM1+/GSTT1+ individuals (4,198 ± 338 and 3,372 ± 183 pg/mL; P = 0.03). The formal interaction of genotype-by-diet was not statistically significant, but the GSTA1/2 increase during the single-dose cruciferous diet was among GSTM1-null/GSTT1-null individuals (by 28%; P = 0.008), largely explained by GSTM1-null/GSTT1-null men (by 41%; P = 0.01). GSTA1/2 increased during the double-dose cruciferous diet in both GSTM1-null/GSTT1-null men (by 35%; P = 0.04) and GSTM1+/GSTT1+ men (by 26%; P = 0.01) but not in women. In summary, cruciferous vegetable supplementation increased GSTA1/2, but the effect was most marked in GSTM1-null/GSTT1-null men. (Cancer Epidemiol Biomarkers Prev 2009;18(11):2974–8)
Rates of Atypical Ductal Hyperplasia Have Declined with Less Use of Postmenopausal Hormone Treatment: Findings from the Breast Cancer Surveillance Consortium
Authors: Menes Tehillah S. , Kerlikowske Karla , Jaffer Shabnam , Seger Deborah , Miglioretti Diana L.
Published: November 2009

Aim: To examine risk factors and rates of atypical ductal hyperplasia (ADH) with and without associated breast cancer over time and tumor characteristics of breast cancer with and without associated ADH in women previously screened with mammography.

Methods: Data on screening mammograms done between 1996 and 2005 were collected from mammography registries that participate in the Breast Cancer Surveillance Consortium. Associations between age, family history of breast cancer, postmenopausal hormone treatment (HT), and final pathology result (ADH or cancer with or without ADH in the same breast) were examined. Rates of different outcomes were calculated per exam year. Tumor characteristics of cancers with and without associated ADH were compared.

Results: A total of 2,453,483 screening mammograms were associated with 1,064 biopsies with ADH, 833 breast cancers with ADH, and 8,161 cancers with no ADH. Postmenopausal HT use decreased significantly from 35% to 11% during the study period. Rates of ADH decreased from a peak of 5.5/10,000 mammograms in 1999 to 2.4/10,000 in 2005. Rates of cancer with ADH decreased from a peak of 4.3/10,000 mammograms in 2003 to 3.3/10,000 in 2005. ADH and breast cancer were significantly associated with use of postmenopausal HT. Cancer associated with ADH was of lower grade and stage and more estrogen receptor positive than cancer with no ADH.

Summary: Postmenopausal HT is associated with an increased risk of ADH with or without cancer. Rates of ADH have decreased over the past decade, which may be partially explained by the significant reduction in use of postmenopausal HT. (Cancer Epidemiol Biomarkers Prev 2009;18(11):2822–8)
Identifying Genes for Establishing a Multigenic Test for Hepatocellular Carcinoma Surveillance in Hepatitis C Virus-Positive Cirrhotic Patients
Authors: Archer Kellie J. , Mas Valeria R. , David Krystle , Maluf Daniel G. , Bornstein Karen , Fisher Robert A.
Published: November 2009

In this study, we used the Affymetrix HG-U133A version 2.0 GeneChips to identify genes capable of distinguishing cirrhotic liver tissues with and without hepatocellular carcinoma by modeling the high-dimensional dataset using an L1 penalized logistic regression model, with error estimated using N-fold cross-validation. Genes identified by gene expression microarray included those that have important links to cancer development and progression, including VAMP2, DPP4, CALR, CACNA1C, and EGR1. In addition, the selected molecular markers in the multigenic gene expression classifier were subsequently validated using reverse transcriptase-real time PCR, and an independently acquired gene expression microarray dataset was downloaded from Gene Expression Omnibus. The multigenetic classifier derived herein did similarly or better than standard abdominal ultrasonography and serum α-fetoprotein, which are currently used for hepatocellular carcinoma surveillance. Because early hepatocellular carcinoma diagnosis increases survival by increasing access to therapeutic options, these molecular markers may prove useful for early diagnosis of hepatocellular carcinoma, especially if prospectively validated and translated into gene products that can be reproducibly and reliably tested noninvasively. (Cancer Epidemiol Biomarkers Prev 2009;18(11):2929–32)
Predisposition for TMPRSS2-ERG Fusion in Prostate Cancer by Variants in DNA Repair Genes
Authors: Luedeke Manuel , Linnert Carmen M. , Hofer Matthias D. , Surowy Harald M. , Rinckleb Antje E. , Hoegel Josef , Kuefer Rainer , Rubin Mark A. , Vogel Walther , Maier Christiane
Published: November 2009

The somatic fusion of TMPRSS2 to ETS oncogenes is a common event in prostate cancer (PCa). We hypothesized that defects in DNA repair may lead to an increase of chromosomal rearrangements and thus to the occurrence of ETS oncogene fusion. We have previously conducted a genome-wide linkage analysis in TMPRSS2-ERG fusion-positive PCa families, revealing potential susceptibility loci on chromosomes 5q14, 9q21, 10q26, 11q24, 12q15, 13q12, 18q, and Xq27. In the present study, nine candidate genes from these regions were selected from the context of DNA repair and screened for mutations in TMPRSS2-ERG fusion-positive families. Thirteen nonsynonymous variants, 5 of which had a minor allele frequency of <0.05, were genotyped in 210 familial cases, 47 of which with a known TMPRSS2-ERG status, 329 sporadic cases, and 512 controls. Significant association of TMPRSS2-ERG fusion-positive PCa was found with rare variants in the genes for POLI [variant F532S: P = 0.0011; odds ratios (OR), 4.62; 95% confidence interval (95% CI), 1.84-11.56] and ESCO1 (variant N191S: P = 0.0034; OR, 4.27; 95% CI, 1.62-11.28). Additional findings, regardless of TMPRSS2-ERG status, were the overrepresentation of a rare BRCA2 variant (V2728I: P = 0.03; OR, 6.16; 95% CI, 1.19-32.00) in familial PCa and of a common allele of RMI1 (variant N455S: P = 0.02; OR, 1.33; 95% CI, 1.04-1.70) in unselected PCa cases. The DNA repair genes POLI and ESCO1 are proposed as susceptibility genes for TMPRSS2-ERG fusion-positive PCa that warrant further investigation. (Cancer Epidemiol Biomarkers Prev 2009;18(11):3030–5)
Dietary Patterns and Prostate Cancer Risk
Authors: Muller David C. , Severi Gianluca , Baglietto Laura , Krishnan Kavitha , English Dallas R. , Hopper John L. , Giles Graham G.
Published: November 2009

Recent studies report that certain dietary patterns, especially those high in red and processed meats, are associated with prostate cancer risk. We prospectively investigated associations between empirically derived dietary patterns and prostate cancer risk using the Melbourne Collaborative Cohort Study. We followed 14,627 men of ages 34 to 75 years for an average of 13.6 years, and identified 1,018 incident prostate cancers. Factor analysis of the 121-item food frequency questionnaire identified four factors with eigenvalues >2 that explained 67% of the total variance. Using Cox proportional hazard models, we found no association between any dietary pattern and prostate cancer risk overall (all Ptrend ≥ 0.2). The hazard ratios for quartiles of the dietary pattern scores ranged from 0.87 to 1.14 and all 95% confidence intervals included 1. The analyses by aggressiveness, Gleason score groups, and age at diagnosis did not show any association (all Ptrend > 0.07). (Cancer Epidemiol Biomarkers Prev 2009;18(11):3126–9)
Mechanisms and Functional Implications of Intestinal Barrier Defects
Authors: Shen Le , Su Liping , Turner Jerrold R.
Published: November 2009

Intestinal epithelial barrier defects, or increased paracellular permeability, were first reported in patients with Crohn’s disease (CD) over 25 years ago. Although increased permeability may herald relapse to active disease, suggesting that impaired barrier function may contribute to progression, limited understanding of the mechanisms that create barrier defects in CD has made it impossible to determine whether increased permeability is a cause or effect of disease. It is now clear that inflammatory cytokines trigger intestinal barrier defects acutely, by cytoskeletal contraction, or chronically, via modulation of tight junction protein expression. Both mechanisms cause barrier dysfunction, but their effects on paracellular size and charge selectivity differ. The clinical ramifications of this distinction are not yet clear. Recent data using in vivo models demonstrate that cytoskeletally mediated barrier dysfunction is sufficient to activate innate and adaptive components of mucosal immunity. Consistent with the presence of increased permeability in some healthy first-degree relatives of CD patients, these barrier defects are insufficient to cause disease in the absence of other stimuli. However, cytoskeletally mediated barrier defects are sufficient to accelerate onset and increase severity of experimental inflammatory bowel disease. Thus, inflammatory cytokines can cause barrier defects and, conversely, barrier defects can activate the mucosal immune system. This raises the possibility that restoration of barrier function may be therapeutic in CD. Consistent with this hypothesis, emerging data indicate that inhibition of cytoskeletally mediated barrier dysfunction may be able to prevent disease progression. Barrier restoration may, therefore, represent a non-immunosuppressive approach to achieving or maintaining disease remission.
Targeted Therapies in Inflammatory Bowel Disease
Authors: Siegmund Britta
Published: November 2009

The pathogenesis of inflammatory bowel disease (IBD) is still not completely understood, however the ongoing research of the last decade is allowing the hypothesis that in genetically predisposed individuals distinct environmental factors result in a dysregulation of the mucosal immune system and thus IBD. Until today the majority of patients are being treated with rather unspecific medications exerting suppressive effects on the mucosal immune system. Nevertheless, theses substances including azathioprine and steroids have proven excellent efficacy for defined subgroups of patients. However, the better understanding of the underlying pathogenesis resulted in the clinical development of novel therapeutic strategies with specific targets. The most prominent example being antibodies targeting tumor necrosis factor-α which are routinely administered in patients suffering from either Crohn’s disease (CD) or ulcerative colitis. A second strategy is targeting the protein subunit p40 which heterodimerizes either with p35 resulting in the pro-inflammatory cytokine IL-12 or with p19 thus forming the pro-inflammatory IL-23. Experimental data suggest a crucial role for both cytokines in experimental colitis. Various antibodies against p40 are currently in clinical trials for patients with CD. In areas of inflammation, the blood vessel endothelial cells upregulate adhesion molecules resulting in the infiltration of leukocytes into the respective area. Natalizumab blocks these adhesion molecules. Treatment with natalizumab was associated with clinical improvement in patients with CD and has been approved in the USA. In summary, several therapeutic targets have already entered our clinical routine and have for some patients resulted in significant changes of the disease course.
Significance of Abdominal Ultrasound in Inflammatory Bowel Disease
Authors: Dietrich C.F.
Published: November 2009

Transabdominal ultrasound is most commonly used to examine the liver, hepatobiliary-pancreatic and urogenital tract. Its use for imaging the intestinal tract is less well established and has been considered more difficult in the past. Improvements in technology and increasing experience with sonographic findings in a variety of intestinal diseases including inflammatory bowel disease (IBD), however, have contributed to firmly establishing the role of ultrasound as a clinically important, non-invasive and widely available imaging modality. In addition, newer techniques such as harmonic imaging and contrast-enhanced ultrasound have recently gained attention. Transabdominal ultrasound is clinically useful in the initial diagnosis of IBD by evaluating bowel wall thickness and surrounding structures including peri-intestinal inflammatory reaction, extent and localization of involved bowel segments and detection of extraluminal complications such as fistula, abscesses, carcinoma and ileus. Transabdominal ultrasound is currently accepted as a clinically important first-line tool in assessing patients with Crohn’s disease irrespective of their clinical symptoms and/or disease activity. It helps to better characterize the course of the disease in individual patients and can guide therapeutic decisions. The topic of this review is to provide an updated overview of the role of transabdominal ultrasound in IBD including Crohn’s disease, ulcerative colitis, tuberculosis and neutropenic colitis while summarizing the results of recent studies with special reference to sensitivity/specificity in detecting the disease and sonomorphologic features to evaluate disease activity and its luminal and extraluminal complications.
Joint Extraintestinal Manifestations in Ulcerative Colitis
Authors: Dorofeyev A.E. , Vasilenko I.V. , Rassokhina O.A.
Published: November 2009

An extraintestinal manifestation (EIM) very often occurs in ulcerative colitis (UC) patients. EIM modifies the natural course of UC and decreases the quality of life in these patients. The aim of this study was to analyze clinical and laboratory findings in UC patients with joint EIM. 319 UC patients were examined. Among them were 131 (41.1%) patients with distal UC, 102 (32.0%) suffered from left-sided UC and 86 (26.9%) had pancolitis. 95 (29.8%) UC patients had joint EIM. Arthritis correlated with extensive forms of UC and was more often determined in patients with left-sided UC and pancolitis. Arthralgia was a prevalent symptom of joint EIM in patients with distal UC. Colon microbiocenosis and the mucosal barrier in UC patients were analyzed. The cytokine status with privileged cytokine profile changes was investigated. In all UC patients, dysbiosis with a decreasing quantity of bifidobacteria, lactobacilli and Ð·scherichia coli was found, but an increase of facultative flora was also found. At the same time, an association of facultative flora in UC patients with arthritis was observed. In these patients, Staphylococcus, Klebsiella and Proteus were found more often in stool cultures. These associations correlated with a modification of the colonocytes’ cell receptor maturity of mucus, a condition with a decreased staining intensity by lectins. A cytokine imbalance with an increase of proinflammatory and a decrease of anti-inflammatory cytokines was found in all UC patients. The privileged cytokine profile changes in UC patients with joint EIM were analyzed. Maximal increases of IL-1 and TNF with decreases of IL-10 in plasma in patients with joint EIM were observed.
The Genetic Basis of Inflammatory Bowel Disease
Authors: Cooney Rachel , Jewell Derek
Published: November 2009

Twin studies and large-scale population studies have confirmed an increased sibling risk for both Crohn’s disease (CD) and ulcerative colitis (UC). Unlike single gene disorders, CD and UC are thought to result from a complex interplay of multiple genes and environmental factors. The confirmation of CARD15/NOD2 as a CD susceptibility gene in the late 1990s caused much excitement in the field of complex diseases in general and since then, the rapid rate of progress in molecular genetics, with the advent of large-scale affordable genotyping techniques, has resulted in large collaborations and the identification of over 30 inflammatory bowel disease (IBD)-associated genes. In particular, the importance of the innate immune system has been reaffirmed with the identification of IRGM and ATG16L1 genes in the autophagy pathway as CD susceptibility genes. Disturbance in the adaptive immune system, in particular the IL-23/Th17 axis, has also shown to be of importance for IBD overall. In this era of genome-wide association studies it may be possible to, at last, identify the multiple genes involved in IBD and thus improve our understanding of the genotype-phenotype correlation and improve treatment.
The Anemia of Heart Failure
Authors: Silverberg Donald S. , Wexler Dov , Palazzuoli Alberto , Iaina Adrian , Schwartz Doron
Published: November 2009

Anemia is common in congestive heart failure (CHF) and is associated with an increased mortality and morbidity. The most likely causes of anemia are chronic kidney disease (CKD) and excessive cytokine production, both of which can cause depression of erythropoietin (EPO) production and bone marrow activity. The cytokines also induce iron deficiency by both reducing gastrointestinal iron absorption and iron release from iron stores located in the macrophages and hepatocytes. Iron deficiency can cause thrombocytosis which might also contribute to cardiovascular complications in both CHF and CKD and is partially reversible with iron treatment. Thus attempts to control this anemia will have to consider both the use of erythropoiesis-stimulating agents (ESA), such as EPO, as well as oral and, probably more importantly, intravenous (IV) iron. The many studies on anemia in CHF patients treated with ESA and oral or IV iron, and even with IV iron without ESA have up to now shown a quite consistent positive effect on hospitalization, fatigue, shortness of breath, quality of life, exercise capacity, and β-natriuretic peptide reduction, in the absence of increased cardiovascular damage related to the therapy. Adequately powered long-term placebo-controlled studies of ESA and/or IV iron are currently being carried out and their results are eagerly awaited.
The Natural History of Untreated HFE-Related Hemochromatosis
Authors: Adams Paul C.
Published: November 2009

Hemochromatosis has generally been considered to be a genetic disease in which progressive iron accumulation over many years can lead to cirrhosis of the liver, hepatocellular carcinoma, diabetes, cardiomyopathy, and arthropathy. Iron depletion by phlebotomy has been the recommended therapy although a randomized trial of phlebotomy versus no treatment has never been reported. Since the discovery of the HFE gene in 1996, it has been possible to predict the risk of developing iron overload by a simple blood test to detect C282Y homozygotes of the HFE gene. The application of the hemochromatosis genetic test in large population studies often initiated to investigate other diseases has provided a fascinating glimpse into the natural history of untreated C282Y homozygotes followed for over 20 years without phlebotomy treatment. These observations are summarized in this review article which raises questions about the need for phlebotomy in all C282Y homozygous patients.
Role of T2* Magnetic Resonance in Monitoring Iron Chelation Therapy
Authors: Carpenter John-Paul , Pennell Dudley J.
Published: November 2009

The monitoring of chelation therapy is a very important part of the management of transfusion-dependent patients. Classical methods of monitoring iron loading are either unreliable or unable to detect important myocardial siderosis which can predispose to the development of cardiac complications such as heart failure. The development of the T2* technique using cardiovascular magnetic resonance has allowed clinicians to have a reliable method for measuring cardiac iron to guide chelation therapy. T2* can identify early those patients who are at risk of developing cardiac complications, enabling personalised, tailored therapy to avoid potential problems.
In vitro Fibroblast and Dermis Fibroblast Activation by Laser Irradiation at Low Energy
Authors: Bosatra M. , Jucci A. , Olliaro P. , Quacci D. , Sacchi S.
Published: November 2009

The effects of laser irradiations have been estimated both from the clinical point of view (rate of reduction of the ulcerated area) and in ultrastructural terms. The modification produced by laser in human fibroblasts in culture have also been investigated. Under our clinical and experimental conditions, laser stimulates the secretion of fibroblasts, both in vivo and in vitro, for reasons that are still the object of research. After irradiation the formation of periodic collagen fibrils is not observed, so that complete ‘restitutio ad integrum’ of the dermal matrix does not occur.
Ticonazole, a New Imidazole-Antifungal Agent for the Treatment of Dermatomycoses
Authors: Marriott M.S. , Baird J.R.C. , Brammer K.W. , Faulkner J.K. , Halliwell G. , Jevons S. , Tarbit M.H.
Published: November 2009

Tioconazole is a new imidazole antifungal agent with broad-spectrum activity. Its in vitro activity against common dermal pathogens is generally better than miconazole by a factor of 2–8. This activity is paralleled by good topical efficacy in a guinea pig dermatomycosis model. Pharmacokinetic studies in animals have demonstrated minimal systemic exposure following dermal application. Acute general pharmacology studies have shown that the compound is well tolerated in animals and unlikely to produce side-effects in man.
Treatment of Dermatomycoses with Topical Tioconazole and Miconazole
Authors: Fredriksson Torsten
Published: November 2009

A total of 60 patients with proven fungal infection of the skin took part in a single-blind comparative study of the efficacy, toleration and safety of tioconazole base 1 % w/w and miconazole nitrate 2% creams applied twice daily for 14 days to patients with pityriasis versicolor and for 28 days to patients with dermatophyte and yeast infections. Overall assessment of the patients reviewed at the end of treatment showed that 23 of 30 patients (77%) treated with tioconazole and 19 of 30 patients (63%) treated with miconazole were clinically and mycologically cured. Tioconazole cured 80% (8 of 10) and miconazole cured 38% (5 of 13) of the infections with Trichophyton rubrum, which are the most frequent ones. At long-term follow-up, approximately 6 weeks later, results in both treatment groups were comparable. 20 of the 23 patients (87%) cured by tioconazole and 18 of the 19 patients (95%) cured by miconazole remained free from infection. Both creams were easy to apply and there were no reports of staining. No side effects were recorded during the study.
Tioconazole in the Treatment of Fungal Infections of the Skin
Authors: O’Neill East M. , Henderson J.T. , Jevons S.
Published: November 2009

In 32 studies involving 1,304 patients tioconazole 1% dermal cream has been shown to be effective and safe in the treatment of a wide variety of superficial fungal infections of the skin and erythrasma. Tioconazole cream is more effective than miconazole nitrate 2% cream in the treatment of pityriasis versicolor and in infections with Trichophyton rubrum and Trichophyton mentagrophytes which cause 70% of dermatophyte infections in man. Data from comparisons with econazole and clotrimazole are too few to allow conclusions to be drawn on relative efficacy. All the creams were easy to apply and there were no serious adverse reactions, local or systemic.
Treatment of Multiple Squamous Cell Carcinomas of the Skin in an Immunosuppressed Patient
Authors: Reymann Flemming
Published: November 2009

A patient receiving immunosuppressive treatment through 7 years after kidney transplantation has developed 84 skin tumors during the last 3½ years. 28 squamous cell carcinomas, which all were histologically highly differentiated, could not clinically be distinguished from 49 keratoses. The problem of therapy is rather delicate. In this case the patient has been followed by regular checkups four times a year and all new tumors have been removed by curettage.
The Sézary Cell in the Blood of Patients with Mycosis Fungoides
Authors: Winkelmann R.K. , Hoagland Clark
Published: November 2009

A study of 96 patients with an original diagnosis of mycosis fungoides revealed that 84 did not have circulating Sézary cells. Of the 12 patients with Sézary cells, only 3 had more than 15%. The 12 patients had benign and malignant skin diseases. The Sézary cell does not seem to have any importance in the pathogenesis of mycosis fungoides.
Repeated Staphylococcal Pyoderma in Two Siblings with Defective Neutrophil Bacterial Killing
Authors: Rebora A. , Crovato F. , Dallegri F. , Patrone F.
Published: November 2009

2 children with undue susceptibility to skin infections and isolated defective neutrophil bacterial killing are described. Since the NBT-reducing capabilities of granulocytes were normal, a mild form of chronic granulomatous disease was excluded. Ascorbic acid was effective in delaying and eventually suppressing infectious episodes.
Assessment of Some Variables Affecting the Blanching Activity of Betamethasone 17-Valerate Cream
Authors: Magnus A.D. , Haigh J.M. , Kanfer I.
Published: November 2009

The effect of concentration and occlusion time on the ability of Betnovate® cream (betamethasone 17-valerate 0.1%) to produce skin blanching was assessed. Generally, increased concentration or occlusion time produce an increase in the degree of blanching observed, however, a plateau stage is eventually reached where no further increase of blanching occurs.