bluuebunny/crossref_metadata_2025 huggingface dataset:
Laparoendoscopic Single-Site Surgery for the Treatment of Benign Adnexal Disease: A Prospective Trial
Authors: Fagotti Anna , Fanfani Francesco , Rossitto Cristiano , Marocco Francesco , Gallotta Valerio , Romano Federico , Scambia Giovanni
Published: February 2010

Background. To validate feasibility, efficacy, and safeness of laparoscopic treatment of benign adnexal diseases through a single transumbilical access (LESS) in a prospective series of patients. Methods. A prospective clinical trial including 30 women has been conducted at the Division of Gynecology of Catholic University of Sacred Hearth of Rome. Patients underwent different laparoscopic procedures by LESS utilizing a multiport trocar and conventional straight laparoscopic instrumentation. Intra and perioperative outcome has been reported. Results. Ten mono/bilateral adnexectomies and 20 cystectomies have been performed by LESS approach. Laparoscopic procedures were completed through a single access in 28 cases (93.4%). No major intra- or postoperative complications were observed. Mean hospital stay was 1.3 days. Conclusions. LESS approach is feasible to treat benign adnexal disease with a very low conversion rate and no early or late complications. More clinical data are needed to confirm these advantages compared to standard laparoscopic technique.
Three-Dimensional Culture of Human Embryonic Stem Cell Derived Hepatic Endoderm and Its Role in Bioartificial Liver Construction
Authors: Sharma Ruchi , Greenhough Sebastian , Medine Claire N. , Hay David C.
Published: February 2010

The liver carries out a range of functions essential for bodily homeostasis. The impairment of liver functions has serious implications and is responsible for high rates of patient morbidity and mortality. Presently, liver transplantation remains the only effective treatment, but donor availability is a major limitation. Therefore, artificial and bioartificial liver devices have been developed to bridge patients to liver transplantation. Existing support devices improve hepatic encephalopathy to a certain extent; however their usage is associated with side effects. The major hindrance in the development of bioartificial liver devices and cellular therapies is the limited availability of human hepatocytes. Moreover, primary hepatocytes are difficult to maintain and lose hepatic identity and function over time even with sophisticated tissue culture media. To overcome this limitation, renewable cell sources are being explored. Human embryonic stem cells are one such cellular resource and have been shown to generate a reliable and reproducible supply of human hepatic endoderm. Therefore, the use of human embryonic stem cell-derived hepatic endoderm in combination with tissue engineering has the potential to pave the way for the development of novel bioartificial liver devices and predictive drug toxicity assays.
Misfit Strain in Superlattices Controlling the Electron-Lattice Interaction via Microstrain in Active Layers
Authors: Poccia Nicola , Ricci Alessandro , Bianconi Antonio
Published: February 2010

High-temperature superconductivity (HTS) emerges in quite different electronic materials: cuprates, diborides, and iron-pnictide superconductors. Looking for unity in the diversity we find in all these materials a common lattice architecture: they are practical realizations of heterostructures at atomic limit made of superlattices of metallic active layers intercalated by spacers as predicted in 1993 by one of us. The multilayer architecture is the key feature for the presence of electronic topological transitions where the Fermi surface of one of the subbands changes dimensionality. The superlattice misfit strain between the active and spacer layers is shown to be a key variable to drive the system to the highest critical temperature that occurs at a particular point of the 3D phase diagram () where is the charge transfer or doping. The plots of as a function of misfit strain at constant charge transfer in cuprates show a first-order quantum critical phase transition where an itinerant striped magnetic phase competes with superconductivity in the proximity of a structural phase transition, that is, associated with an electronic topological transition. The shape resonances in these multigap superconductors is associated with the maximum .
Evolution and Prospects for Intracranial Pharmacotherapy for Refractory Epilepsies: The Subdural Hybrid Neuroprosthesis
Authors: Ludvig Nandor , Medveczky Geza , French Jacqueline A. , Carlson Chad , Devinsky Orrin , Kuzniecky Ruben I.
Published: February 2010

Intracranial pharmacotherapy is a novel strategy to treat drug refractory, localization-related epilepsies not amenable to resective surgery. The common feature of the method is the use of some type of antiepileptic drug (AED) delivery device placed inside the cranium to prevent or stop focal seizures. This distinguishes it from other nonconventional methods, such as intrathecal pharmacotherapy, electrical neurostimulation, gene therapy, cell transplantation, and local cooling. AED-delivery systems comprise drug releasing polymers and neuroprosthetic devices that can deliver AEDs into the brain via intraparenchymal, ventricular, or transmeningeal routes. One such device is the subdural Hybrid Neuroprosthesis (HNP), designed to deliver AEDs, such as muscimol, into the subdural/subarachnoid space overlaying neocortical epileptogenic zones, with electrophysiological feedback from the treated tissue. The idea of intracranial pharmacotherapy and HNP treatment for epilepsy originated from multiple sources, including the advent of implanted medical devices, safety data for intracranial electrodes and catheters, evidence for the seizure-controlling efficacy of intracerebral AEDs, and further understanding of the pathophysiology of focal epilepsy. Successful introduction of intracranial pharmacotherapy into clinical practice depends on how the intertwined scientific, engineering, clinical, neurosurgical and regulatory challenges will be met to produce an effective and commercially viable device.
Altered Expression of Apoptosis Biomarkers in Human Colorectal Microadenomas
Authors: Sena Paola , Roncucci Luca , Marzona Laura , Mariani Francesco , Maffei Stefania , Manenti Antonio , De Pol Anto
Published: February 2010

Human colorectal microadenomas are considered the earliest detectable premalignant lesions in the colon. They can be identified as aggregates of enlarged crypts with thicker epithelial linings and elongated luminal openings on the colonic mucosal surface after methylene blue staining and observation under a dissecting microscope. Multiple lines of evidence suggest that a central role in neoplastic development is played by the inhibition of apoptosis, followed by disruption of DNA repair. Understanding the early mechanisms of colorectal carcinogenesis may help develop new approaches of colorectal cancer prevention and treatment. The aim of the present study was to quantify poly-ADP ribose polymerase 1 (PARP-1)–positive cells and to evaluate apoptotic control mechanisms through Caspase-3 active and Bcl-2 protein expression in human microadenomas and in normal colorectal mucosa using immunofluorescence techniques coupled with confocal microscopy and immunoblot experiments. The mean percentage of PARP-1–positive epithelial cells was 3.0 ± 0.37% (SD) and 15.67 ± 0.40% in microadenoma and in normal mucosa, respectively. Proteins involved in programmed cell death were differently expressed in microadenoma and in normal mucosa. Indeed, by semiquantitative immunoflourescence analysis, confirmed by Western blot, microadenoma showed high levels of Caspase-3 active and low levels of Bcl-2 expression, whereas the opposite was true for normal colorectal mucosa. In the stroma of normal colorectal mucosa, fibroblast-like cells and neutrophils were the cells that underwent apoptosis to a greater extent. In conclusion, malfunction of the control mechanisms of programmed cell death seems present in the early stages of colorectal cancer development. Cancer Epidemiol Biomarkers Prev; 19(2); 351–7
Circulating Steroid Hormone Levels and Risk of Breast Cancer for Postmenopausal Women
Authors: Baglietto Laura , Severi Gianluca , English Dallas R. , Krishnan Kavitha , Hopper John L. , McLean Catriona , Morris Howard A. , Tilley Wayne D. , Giles Graham G.
Published: February 2010

Epidemiologic studies have consistently reported that endogenous steroid hormone levels are associated with postmenopausal breast cancer risk, but little is known on the associations by tumor grade, hormone receptor status, or age at diagnosis.

We performed a case-cohort study of naturally postmenopausal women within the Melbourne Collaborative Cohort Study that included a random sample of 857 women and 197 breast cancer cases diagnosed during a mean of 9.2 years of follow-up. Concentrations of total estradiol, estrone sulfate, testosterone, DHEA sulfate, androstenedione, and sex hormone binding globulin were measured in plasma collected at baseline before diagnosis; free estradiol plasma concentration was calculated. Cox regression was used to estimate associations adjusted for known and potential confounders.

The HR for breast cancer comparing fourth and first quartiles was 1.44 [95% confidence interval (95% CI), 0.89-2.35] for total estradiol, 1.75 (95% CI, 1.06, 2.89) for free estradiol, 2.05 (95% CI, 1.24-3.37) for estrone sulfate, 1.25 (95% CI, 0.78-2.01) for testosterone, 1.41 (95% CI, 0.88-2.27) for DHEA sulfate, 1.49 (95% CI, 0.91-2.44) for androstenedione, and 0.33 (95% CI, 0.19-0.55) for sex hormone binding globulin. These associations did not differ by tumor grade and estrogen receptor/progesterone receptor status (all test for heterogeneity, P > 0.05). Risks associated with estrogen and androgen levels were stronger at older ages (test for interaction across age groups, P = 0.59 for total estradiol and P = 0.01 for testosterone).

Our prospective study confirms earlier findings and suggests that the associations of endogenous hormones with postmenopausal breast cancer risk are independent of tumor grade, and hormone receptor status and might increase in strength with age. Cancer Epidemiol Biomarkers Prev; 19(2); 492–502
Diagnosis of Gastric Malignancy Using Gastric Juice α1-antitrypsin
Authors: Hsu Ping-I , Chen Chung-Hsuan , Hsiao Michael , Wu Deng-Chyang , Lin Ching-Yi , Lai Kwok-Hung , Lu Pei-Jung
Published: February 2010

No accurate, inexpensive, and noninvasive test for gastric cancer screening is currently available. Our recent study identified α1-antitrypsin as a potential biomarker of gastric cancer in gastric juice. The aim of this study was to develop a novel noninvasive modality for detecting gastric cancer by measurement of α1-antitrypsin concentration in gastric juice. The work consisted of two parts: (a) investigating the differences in gastric juice α1-antitrypsin concentrations between gastric cancer patients and controls, and (b) screening gastric cancer using string test to obtain gastric juice followed by immunoassay for α1-antitrypsin concentration. The data showed that gastric juice α1-antitrypsin concentration was markedly higher in gastric cancer patients than in healthy subjects, gastric ulcer patients, and duodenal ulcer patients (all P < 0.001). The area under the receiver operating characteristic curve for identifying gastric cancer cases was 0.96 (95% confidence interval, 0.93-0.99; P < 0.001). The sensitivity and specificity of gastric juice α1-antitrypsin concentration were 96% and 92%, respectively. Gastric juice α1-antitrypsin assay through string test was validated in 93 consecutive patients for gastric cancer screening. The sensitivity and specificity of gastric juice α1-antitrypsin string test at 85% accuracy were 74% and 88%, respectively. The area under the receiver operating characteristic curve for identifying gastric cancer was 0.84. In conclusion, gastric juice α1-antitrypsin concentration in gastric cancer patients markedly exceeds those in healthy subjects and patients with benign gastrointestinal diseases. A noninvasive α1-antitrypsin string test may serve as a new screening tool for identifying gastric cancer patients. Cancer Epidemiol Biomarkers Prev; 19(2); 405–11
Epidemiologic Factors Associated with Seropositivity to Human Papillomavirus Type 16 and 18 Virus–Like Particles and Risk of Subsequent Infection in Men
Authors: Lu Beibei , Hagensee Michael E. , Lee Ji-Hyun , Wu Yougui , Stockwell Heather G. , Nielson Carrie M. , Abrahamsen Martha , Papenfuss Mary , Harris Robin B. , Giuliano Anna R.
Published: February 2010

Our understanding of humoral response to human papillomavirus (HPV) infection has been mainly derived from studies in women. The role of serum antibodies in the natural history of HPV in men has yet to be investigated. Data from 285 male participants of a natural history study were used to determine the epidemiologic factors associated with HPV 16/18 seropositivity and explore the role of HPV 16 and 18 serum antibodies in subsequent HPV infections. Serum antibodies were detected by use of HPV 16– and 18 virus–like particles enzyme-linked immunoassay. Logistic regression and Generalized Estimating Equation was used for the evaluation of risk factors. The risk of subsequent HPV infection by baseline antibody status was assessed by incidence rate ratio and its confidence intervals. Men ages 36 to 44 years compared with men ages 18 to 25 years were four times more likely to be seropositive to HPV 16/18. In addition, being divorced, separated, or widowed; being a former smoker; and having sex with men was positively and independently associated with HPV 16/18 seropositivity. Our findings on the potential role of HPV 16 or 18 serum antibodies in subsequent infection were inconclusive. Large prospective studies are warranted to adequately address questions on the role of natural immunity in the natural history of HPV infections in men. Cancer Epidemiol Biomarkers Prev; 19(2); 511–6
Cumulative Effect of Multiple Loci on Genetic Susceptibility to Familial Lung Cancer
Authors: Liu Pengyuan , Vikis Haris G. , Lu Yan , Wang Yian , Schwartz Ann G. , Pinney Susan M. , Yang Ping , de Andrade Mariza , Gazdar Adi , Gaba Colette , Mandal Diptasri , Lee Juwon , Kupert Elena , Seminara Daniela , Minna John , Bailey-Wilson Joan E. , Amos Christopher I. , Anderson Marshall W. , You Ming
Published: February 2010

Background: Genetic factors play important roles in lung cancer susceptibility. In this study, we replicated the association of 5p15.33 and 6p21.33 with familial lung cancer. Taking into account the previously identified genetic susceptibility variants on 6q23-25/RGS17 and 15q24-25.1, we further determined the cumulative association of these four genetic regions and the population attributable risk percent of familial lung cancer they account for.

Methods: One hundred ninety-four case patients and 219 cancer-free control subjects from the Genetic Epidemiology of Lung Cancer Consortium were used for the association analysis. Each familial case was chosen from one high-risk lung cancer family that has three or more affected members. Single nucleotide polymorphisms (SNP) on chromosomal regions 5p15.33, 6p21.33, 6q23-25/RGS17, and 15q24-25.1 were assessed for their associations with familial lung cancer. The cumulative association of the four chromosomal regions with familial lung cancer was evaluated with the use of a linear logistic model. Population attributable risk percent was calculated for each SNP using risk ratio.

Results: SNP rs31489 showed the strongest evidence of familial lung cancer association on 5p15.33 (P = 2 × 10−4; odds ratio, 0.57; 95% confidence interval, 0.42-0.77), whereas rs3117582 showed a weak association on 6p21.33 (P = 0.09; odds ratio, 1.47; 95% confidence interval, 0.94-2.31). Analysis of a combination of SNPs from the four regions provided a stronger cumulative association with familial lung cancer (P = 6.70 × 10−6) than any individual SNPs. The risk of lung cancer was increased to 3- to 11-fold among those subjects who had at least one copy of risk allele at each region compared with subjects without any of the risk factors. These four genetic regions contribute to a total of 34.6% of familial lung cancer in smokers.

Conclusions: The SNPs in four chromosomal regions have a cumulative and significant association with familial lung cancer and account for about one-third of the population attributable risk for familial lung cancer. Cancer Epidemiol Biomarkers Prev; 19(2); 517–24
Soft Drink and Juice Consumption and Risk of Pancreatic Cancer: The Singapore Chinese Health Study
Authors: Mueller Noel T. , Odegaard Andrew , Anderson Kristin , Yuan Jian-Min , Gross Myron , Koh Woon-Puay , Pereira Mark A.
Published: February 2010

Background: Sugar-sweetened carbonated beverages (called soft drinks) and juices, which have a high glycemic load relative to other foods and beverages, have been hypothesized as pancreatic cancer risk factors. However, data thus far are scarce, especially from non-European descent populations. We investigated whether higher consumption of soft drinks and juice increases the risk of pancreatic cancer in Chinese men and women.

Methods: A prospective cohort analysis was done to examine the association between soft drink and juice consumption and the risk of pancreatic cancer in 60,524 participants of the Singapore Chinese Health Study with up to 14 years of follow-up. Information on consumption of soft drinks, juice, and other dietary items, as well as lifestyle and environmental exposures, was collected through in-person interviews at recruitment. Pancreatic cancer cases and deaths were ascertained by record linkage of the cohort database with records of population-based Singapore Cancer Registry and the Singapore Registry of Births and Deaths.

Results: The first 14 years for the cohort resulted in cumulative 648,387 person-years and 140 incident pancreatic cancer cases. Individuals consuming ≥2 soft drinks/wk experienced a statistically significant increased risk of pancreatic cancer (hazard ratio, 1.87; 95% confidence interval, 1.10-3.15) compared with individuals who did not consume soft drinks after adjustment for potential confounders. There was no statistically significant association between juice consumption and risk of pancreatic cancer.

Conclusion: Regular consumption of soft drinks may play an independent role in the development of pancreatic cancer. Cancer Epidemiol Biomarkers Prev; 19(2); 447–55
Single and Multivariate Associations of MSR1, ELAC2, and RNASEL with Prostate Cancer in an Ethnic Diverse Cohort of Men
Authors: Beuten Joke , Gelfond Jonathan A.L. , Franke Jennifer L. , Shook Stacey , Johnson-Pais Teresa L. , Thompson Ian M. , Leach Robin J.
Published: February 2010

Three genes, namely, ELAC2 (HPC2 locus) on chromosome 17p11, 2′-5′-oligoisoadenlyate-synthetase-dependent ribonuclease L (RNASEL, HPC1 locus), and macrophage scavenger receptor 1 (MSR1) within a region of linkage on chromosome 8p, have been identified as hereditary tumor suppressor genes in prostate cancer. We genotyped 41 tagged single nucleotide polymorphisms (SNPs) covering the three genes in a case-control cohort, which included 1,436 Caucasians, 648 Hispanics, and 270 African Americans. SNPs within MSR1, ELAC2, and RNASEL were significantly associated with risk of prostate cancer albeit with differences among the three ethnic groups (P = 0.043-1.0 × 10−5). In Caucasians, variants within MSR1 and ELAC2 are most likely to confer prostate cancer risk, and rs11545302 (ELAC2) showed a main effect independent of other significant SNPs (P = 2.03 × 10−5). A major haplotype G-A-C-G-C-G combining five SNPs within MSR1 was further shown to increase prostate cancer risk significantly in this study group. Variants in RNASEL had the strongest effects on prostate cancer risk estimates in Hispanics and also showed an interaction effect of family history. In African Americans, single SNPs within MSR1 were significantly associated with prostate cancer risk. A major risk haplotype C-G-G-C-G of five SNPs within ELAC2 was found in this group. Combining high-risk genotypes of MSR1 and ELAC2 in Caucasians and of RNASEL and MSR1 in Hispanics showed synergistic effects and suggest that an interaction between both genes in each ethnicity is likely to confer prostate cancer risk. Our findings corroborate the involvement of ELAC2, MSR1, and RNASEL in the etiology of prostate cancer even in individuals without a family history. Cancer Epidemiol Biomarkers Prev; 19(2); 588–99
Aldehyde Dehydrogenase 1 A1–Positive Cell Population Is Enriched in Tumor-Initiating Cells and Associated with Progression of Bladder Cancer
Authors: Su Yun , Qiu Qi , Zhang Xingqiao , Jiang Zhengran , Leng Qixin , Liu Zhenqiu , Stass Sanford A. , Jiang Feng
Published: February 2010

Aldehyde dehydrogenase 1 A1 (ALDH1A1) has recently been suggested as a marker for cancer stem or stem-like cancer cells of some human malignancies. The purpose of this study was to investigate the stem cell–related function and clinical significance of the ALDH1A1 in bladder urothelial cell carcinoma. Aldefluor assay was used to isolate ALDH1A1+ cells from bladder cancer cells. Stem cell characteristics of the ALDH1A1+ cells were then investigated by in vitro and in vivo approaches. Immunohistochemistry was done for evaluating ALDH1A1 expression on 22 normal bladder tissues and 216 bladder tumor specimens of different stage and grade. The ALDH1A1+ cancer cells displayed higher in vitro tumorigenicity compared with isogenic ALDH1A1− cells. The ALDH1A1+ cancer cells could generate xenograft tumors that resembled the histopathologic characteristics and heterogeneity of the parental cells. High ALDH1A1 expression was found in 26% (56 of 216) of human bladder tumor specimens and significantly related to advanced pathologic stage, high histologic grade, recurrence and progression, and metastasis of bladder urothelial cell carcinomas (all P < 0.05). Furthermore, ALDH1A1 expression was inversely associated with cancer-specific and overall survivals of the patients (P = 0.027 and 0.030, respectively). Therefore, ALDH1A1+ cell population could be enriched in tumor-initiating cells. ALDH1A1 may serve as a useful marker for monitoring the progression of bladder tumor and identifying bladder cancer patients with poor prognosis who might benefit from adjuvant and effective treatments. Cancer Epidemiol Biomarkers Prev; 19(2); 327–37
Genetic Variation in Prostaglandin E2 Synthesis and Signaling, Prostaglandin Dehydrogenase, and the Risk of Colorectal Adenoma
Authors: Poole Elizabeth M. , Hsu Li , Xiao Liren , Kulmacz Richard J. , Carlson Christopher S. , Rabinovitch Peter S. , Makar Karen W. , Potter John D. , Ulrich Cornelia M.
Published: February 2010

Background: Prostaglandins are important inflammatory mediators; prostaglandin E2 (PGE2) is the predominant prostaglandin in colorectal neoplasia and affects colorectal carcinogenesis. Prostaglandins are metabolites of ω-6 and ω-3 polyunsaturated fatty acids; their biosynthesis is the primary target of nonsteroidal anti-inflammatory drugs (NSAID), which reduce colorectal neoplasia risk.

Methods: We investigated candidate and tagSNPs in PGE2 synthase (PGES), PGE2 receptors (EP2 and EP4), and prostaglandin dehydrogenase (PGDH) in a case-control study of adenomas (n = 483) versus polyp-free controls (n = 582) and examined interactions with NSAID use or fish intake, a source of ω-3 fatty acids.

Results: A 30% adenoma risk reduction was observed for EP2 4950G>A (intron 1; ORGA/AA vs. GG, 0.71; 95% confidence interval, 0.52-0.99). For the candidate polymorphism EP4 Val294Ile, increasing fish intake was associated with increased adenoma risk among those with variant genotypes, but not among those with the Val/Val genotype (Pinteraction = 0.02). An interaction with fish intake was also observed for PGES −664A>T (5′ untranslated region; Pinteraction = 0.01). Decreased risk with increasing fish intake was only seen among those with the AT or TT genotypes (OR>2 t/wk vs. <1 t/wk, 0.56; 95% confidence interval, 0.28-1.13). We also detected interactions between NSAIDs and EP2 9814C>A (intron 1) and PGDH 343C>A (intron 1). However, none of the observed associations was statistically significant after adjustment for multiple testing. We investigated potential gene-gene interactions using the Chatterjee 1 degree of freedom Tukey test and logic regression; neither method detected significant interactions.

Conclusions: These data provide little support for associations between adenoma risk and genetic variability related to PGE2, yet suggest gene-environment interactions with anti-inflammatory exposures. Cancer Epidemiol Biomarkers Prev; 19(2); 547–57
Family History, Mammographic Density, and Risk of Breast Cancer
Authors: Martin Lisa J. , Melnichouk Olga , Guo Helen , Chiarelli Anna M. , Hislop T. Gregory , Yaffe Martin J. , Minkin Salomon , Hopper John L. , Boyd Norman F.
Published: February 2010

Purpose: Mammographic density is a strong and highly heritable risk factor for breast cancer. The purpose of this study was to examine the extent to which mammographic density explains the association of family history of breast cancer with risk of the disease.

Subjects and Methods: We carried out three nested case-control studies in screening programs that included in total 2,322 subjects (1,164 cases and 1,158 controls). We estimated the independent and combined associations of family history and percent mammographic density at baseline with subsequent breast cancer risk.

Results: After adjustment for age and other risk factors, compared with women with no affected first-degree relatives, percent mammographic density was 3.1% greater for women with one affected first-degree relative, and 7.0% greater for women with two or more affected relatives (P = 0.001 for linear trend across family history categories). The odds ratios for breast cancer risk were 1.37 [95% confidence interval (95% CI), 1.10-1.72] for having one affected relative, and 2.45 (95% CI, 1.30-4.62) for having two or more affected relatives (P for trend = 0.0002). Adjustment for percent mammographic density reduced these odds ratios by 16% and 14%, respectively. Percent mammographic density explained 14% (95% CI, 4-39%) of the association of family history (at least one affected first-degree relative) with breast cancer risk.

Conclusions: Percent mammographic density has features of an intermediate marker for breast cancer, and some of the genes that explain variation in percent mammographic density might be associated with familial risk of breast cancer. Cancer Epidemiol Biomarkers Prev; 19(2); 456–63
Comparison of Second Cancer Risks from Brachytherapy and External Beam Therapy After Uterine Corpus Cancer
Authors: Lönn Stefan , Gilbert Ethel S. , Ron Elaine , Smith Susan A. , Stovall Marilyn , Curtis Rochelle E.
Published: February 2010

Background: Adjuvant radiotherapy is common for uterine corpus cancer patients, yet the long-term carcinogenic effects of different types of radiotherapy have not been studied adequately.

Methods: Second primary cancer risks were quantified in a cohort of 60,949 individuals surviving ≥1 year of uterine corpus cancer diagnosed from 1973 to 2003 in Surveillance, Epidemiology and End Results Program cancer registries. Incidence rate ratios (IRR) were estimated by comparing patients treated with surgery plus various types of radiotherapy with patients receiving surgery only.

Results: The IRRs of a second cancer were increased among irradiated patients compared with patients having surgery only [combination radiotherapy, IRR = 1.26; 95% confidence interval (CI), 1.16-1.36; external beam therapy, IRR = 1.15; 95% CI CI, 1.08-1.22; brachytherapy, IRR = 1.07; 95% CI, 1.00-1.16]. IRRs were highest for heavily irradiated sites (that is colon, rectum, and bladder) and for leukemia following any external beam therapy, with the largest risks for solid cancers among 10-year survivors. Any external beam therapy had a 44% higher cancer risk at heavily irradiated sites than brachytherapy when the two treatments were directly compared (5-year survivors: IRR = 1.44; 95% CI, 1.19-1.75). We estimated that of 2,012 solid cancers developing ≥5 years after irradiation, 213 (11%) could be explained by radiotherapy.

Conclusions: Radiotherapy for uterine cancer increases the risk of leukemia and second solid cancers at sites in close proximity to the uterus, emphasizing the need for continued long-term surveillance for new malignancies. The overall risk of a second cancer was lower following brachytherapy compared with any external beam radiotherapy. Cancer Epidemiol Biomarkers Prev; 19(2); 464–74
Diabetes Genes and Prostate Cancer in the Atherosclerosis Risk in Communities Study
Authors: Meyer Tamra E. , Boerwinkle Eric , Morrison Alanna C. , Volcik Kelly A. , Sanderson Maureen , Coker Ann L. , Pankow James S. , Folsom Aaron R.
Published: February 2010

There is a known inverse association between type 2 diabetes (T2D) and prostate cancer (PrCa) that is poorly understood. Genetic studies of the T2D-PrCa association may provide insight into the underlying mechanisms of this association. We evaluated associations in the Atherosclerosis Risk in Communities study between PrCa and nine T2D single nucleotide polymorphisms from genome-wide association studies of T2D (in CDKAL1, CDKN2A/B, FTO, HHEX, IGF2BP2, KCNJ11, PPARG, SLC30A8, and TCF7L2) and four T2D single nucleotide polymorphisms from pre–genome-wide association studies (in ADRB2, CAPN10, SLC2A2, and UCP2). From 1987 to 2000, there were 397 incident PrCa cases among 6,642 men ages 45 to 64 years at baseline. We used race-adjusted Cox proportional hazards models to estimate associations between PrCa and increasing number of T2D risk-raising alleles. PrCa was positively associated with the CAPN10 rs3792267 G allele [hazard ratio (HR) 1.20; 95% confidence interval (CI), 1.00-1.44] and inversely associated with the SLC2A2 rs5400 Thr110 allele (HR, 0.85; 95% CI, 0.72, 1.00), the UCP2 rs660339 Val55 allele (HR, 0.84; 95% CI, 0.73, 0.97) and the IGF2BP2 rs4402960 T allele (HR, 0.79; 95% CI, 0.61-1.02; blacks only). The TCF7L2 rs7903146 T allele was inversely associated with PrCa using a dominant genetic model (HR, 0.79; 95% CI, 0.65-0.97). Further knowledge of T2D gene-PrCa mechanisms may improve understanding of PrCa etiology. Cancer Epidemiol Biomarkers Prev; 19(2); 558–65
Behavioral Correlates of HPV Vaccine Acceptability in the 2007 Health Information National Trends Survey (HINTS)
Authors: Fang Carolyn Y. , Coups Elliot J. , Heckman Carolyn J.
Published: February 2010

The development of a prophylactic vaccine to prevent infection with oncogenic subtypes of human papillomavirus (HPV) is an important step in reducing cervical cancer incidence and mortality. However, national data indicate that only 37% of 13- to 17-year-old females have initiated the vaccine series. Prior studies have examined demographic, medical history, and psychosocial variables associated with parental HPV vaccine acceptability, although few have investigated the behavioral correlates of vaccine acceptability. The primary purpose of the current study is to report on national acceptability of the HPV vaccine among U.S. adults with female children in the household and to investigate the health behavior correlates of vaccine acceptability. Data were drawn from the 2007 Health Information National Trends Survey (HINTS). The study sample comprised 1,383 adults who reported having a female child under the age of 18 in their household (52% female, 59% white; mean age = 40 years). More than half (58%) reported they would have a daughter get the HPV vaccine, 25% were not sure, and 18% would not have a daughter vaccinated. Behavioral factors significantly associated with lower acceptance of the HPV vaccine included lack of physical activity in the past month (P = 0.002), past year use of complementary or alternative therapies (P = 0.021), and no history of smoking (P = 0.005). These results suggest that behavioral health factors may be associated with vaccine acceptability and further our understanding of how behavioral patterns may contribute to the uptake of new cancer prevention strategies. Cancer Epidemiol Biomarkers Prev; 19(2); 319–26
Prevalence of Tamoxifen Use for Breast Cancer Chemoprevention Among U.S. Women
Authors: Waters Erika A. , Cronin Kathleen A. , Graubard Barry I. , Han Paul K. , Freedman Andrew N.
Published: February 2010

Background: Tamoxifen can reduce the risk of developing invasive estrogen receptor–positive breast cancer by 49%, but it is unknown how many women in the United States are taking tamoxifen for primary prevention of breast cancer.

Methods: Data from the years 2000 and 2005 National Health Interview Surveys were analyzed to estimate the prevalence of tamoxifen use among U.S. women for primary chemoprevention of breast cancer.

Results: In 2000, ∼0.2% of U.S. women ages 40 to 79 years without a personal history of breast cancer took tamoxifen for chemoprevention (95% confidence interval, 0.13-0.31). In 2005, the prevalence was ∼0.08% (95% confidence interval, 0.03-0.17).

Conclusion: The prevalence of tamoxifen use for primary prevention of breast cancer was very low in the years 2000 and 2005. Possible explanations for the low uptake are explored. Cancer Epidemiol Biomarkers Prev; 19(2); 443–6
Detection of Tumor Epidermal Growth Factor Receptor Pathway Dependence by Serum Mass Spectrometry in Cancer Patients
Authors: Chung Christine H. , Seeley Erin H. , Roder Heinrich , Grigorieva Julia , Tsypin Maxim , Roder Joanna , Burtness Barbara A. , Argiris Athanassios , Forastiere Arlene A. , Gilbert Jill , Murphy Barbara , Caprioli Richard M. , Carbone David P. , Cohen Ezra E.W.
Published: February 2010

Background: We hypothesized that a serum proteomic profile predictive of survival benefit in non–small cell lung cancer patients treated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) reflects tumor EGFR dependency regardless of site of origin or class of therapeutic agent.

Methods: Pretreatment serum or plasma from 230 patients treated with cetuximab, EGFR-TKIs, or chemotherapy for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) or colorectal cancer (CRC) were analyzed by mass spectrometry. Each sample was classified into “good” or “poor” groups using VeriStrat, and survival analyses of each cohort were done based on this classification. For the CRC cohort, this classification was correlated with the tumor EGFR ligand levels and KRAS mutation status.

Results: In the EGFR inhibitor–treated cohorts, the classification predicted survival (HNSCC: gefitinib, P = 0.007 and erlotinib/bevacizumab, P = 0.02; CRC: cetuximab, P = 0.0065) whereas the chemotherapy cohort showed no survival difference. For CRC patients, tumor EGFR ligand RNA levels were significantly associated with the proteomic classification, and combined KRAS and proteomic classification provided improved survival classification.

Conclusions: Serum proteomic profiling can detect clinically significant tumor dependence on the EGFR pathway in non–small cell lung cancer, HNSCC, and CRC patients treated with either EGFR-TKIs or cetuximab. This classification is correlated with tumor EGFR ligand levels and provides a clinically practical way to identify patients with diverse cancer types most likely to benefit from EGFR inhibitors. Prospective studies are necessary to confirm these findings. Cancer Epidemiol Biomarkers Prev; 19(2); 358–65
Nonsteroidal Anti-Inflammatory Drugs and Risk for Ovarian and Endometrial Cancers in the Iowa Women's Health Study
Authors: Prizment Anna E. , Folsom Aaron R. , Anderson Kristin E.
Published: February 2010

Background: Several epidemiologic studies have shown inverse associations between use of nonsteroidal anti-inflammatory drugs (NSAID) and incident ovarian cancer, but the results are inconsistent. There have been only a few studies examining possible links between NSAIDs and endometrial cancer risk. We investigated associations between use of NSAIDs and incident ovarian and endometrial cancers in a prospective cohort of about 20,000 women with ages from 58 to 76 years in 1992. Participants were asked how often they used aspirin and nonaspirin NSAIDs. Over 15 years, 311 endometrial and 167 ovarian incident malignancies were identified. Multivariate-adjusted hazard ratios were estimated using Cox proportional regression.

Results: Compared with women who reported no use of aspirin, the relative risks for ovarian cancer for those who used aspirin <2, 2 to 5 times, and ≥6 times per week were 0.83, 0.77, and 0.61, respectively (P trend = 0.04). We did not observe any association between nonaspirin NSAIDs use and ovarian cancer risk. Neither did we find associations between aspirin or nonaspirin NSAIDs use and risk for endometrial cancer.

Conclusions: Our results suggest a possible inverse association between frequency of aspirin use and risk for ovarian cancer. Cancer Epidemiol Biomarkers Prev; 19(2); 435–42
Association of Global Levels of Histone Modifications with Recurrence-Free Survival in Stage IIB and III Esophageal Squamous Cell Carcinomas
Authors: I Hoseok , Ko Eunkyung , Kim Yujin , Cho Eun Yoon , Han Joungho , Park Joobae , Kim Kwhanmien , Kim Duk-Hwan , Shim Young Mog
Published: February 2010

This study was aimed at understanding the effects of histone modifications on recurrence-free survival (RFS) after esophagectomy in esophageal squamous cell carcinoma (ESCC). The acetylation of histone H3 lysine (H3K9Ac), histone H3 lysine 18 (H3K18Ac), and histone H4 lysine 12 (H4K12Ac), and the dimethylation of histone H3 lysine 9 (H3K9diMe) and histone H4 arginine 3 (H4R3diMe) were analyzed by immunohistochemistry in 237 ESCCs. The K-means clustering algorithm was used to identify unique patterns of histone modifications. At a median follow-up of 5.1 years, 109 (46%) of 237 patients had developed recurrence of disease. Mean global levels of H3K9Ac, H3K18Ac, H3K9diMe, H4K12Ac, and H4R3diMe were 81.5%, 65.1%, 80.3%, 45.9%, and 27.4%, respectively. In the analysis of individual histones, a 1% increase in the global level of H3K18Ac in pathologic stage III worsened RFS at 1.009 times [95% confidence interval (CI), 1.001-1.016; P = 0.03], after adjusting for age, sex, and operative method. Cluster analysis also showed significant effects of histone modifications on RFS. For stage IIB cancers, Cox proportional hazards analysis showed that RFS of cluster 1, with high global levels of H3K18Ac and H4R3diMe, was 2.79 times poorer (95% CI, 1.14-6.27; P = 0.008) than that of cluster 2, with low levels. RFS for stage III cancers was also poorer in cluster 1 than cluster 2 (adjusted hazard ratio, 2.42; 95% CI, 1.10-5.34; P = 0.02). In conclusion, the present study suggests that global levels of histone modifications in ESCC may be an independent prognostic factor of RFS. Cancer Epidemiol Biomarkers Prev; 19(2); 566–73
A Systematic Review of p53 as a Prognostic Factor of Survival in Squamous Cell Carcinoma of the Four Main Anatomical Subsites of the Head and Neck
Authors: Tandon Sankalap , Tudur-Smith Catrin , Riley Richard D. , Boyd Mark T. , Jones Terence M.
Published: February 2010

Objectives: To summarize existing evidence about whether the presence of mutant or upregulated p53 is a prognostic factor for patients presenting with squamous cell carcinoma arising from the larynx, oropharynx, hypopharynx, or oral cavity.

Method: Relevant articles were identified using strict criteria for systematic searches. Associations between mutant or upregulated p53 versus wild-type or low/undetectable p53 in relation to overall survival and DFS were summarized by extracting or deriving hazard ratio (HR) estimates. Random-effects meta-analyses were used to account for between-study heterogeneity and to summarize the effect of p53 across studies.

Results: The meta-analyses gave a statistically significant pooled HR for overall survival in oral cavity [pooled HR, 1.48; 95% confidence interval, (95% CI), 1.03-2.11], and for disease-free survival in oral cavity (pooled HR, 1.47; 95% CI, 1.12-1.93) and in oropharynx (pooled HR, 0.45; 95% CI, 0.27-0.73). Despite attempts to limit it, between-study heterogeneity was large in the majority of meta-analyses and the prognostic value of p53 was generally inconsistent and inconclusive across studies.

Conclusion: The meta-analysis results highlight that current evidence about the prognostic value of p53 in patients with squamous cell carcinaoma of the head and neck is inconclusive. Large heterogeneity exists across studies in study-level and patient-level characteristics, making it difficult to ascertain a clear picture. Future studies are required in which p53 expression is investigated in a more standardized and biologically informative manner. In particular, prospectively planned individual patient data meta-analyses are needed to establish the prognostic importance of p53 for specific subgroups of patients undergoing specific treatments. Cancer Epidemiol Biomarkers Prev; 19(2); 574–87
Concurrent Infection with Multiple Human Papillomavirus Types: Pooled Analysis of the IARC HPV Prevalence Surveys
Authors: Vaccarella Salvatore , Franceschi Silvia , Snijders Peter J.F. , Herrero Rolando , Meijer Chris J.L.M. , Plummer Martyn ,   the IARC HPV Prevalence Surveys Study Group
Published: February 2010

To understand viral interactions and the cross-reactivity of natural or vaccine-induced responses, we investigated whether multiple human papillomavirus (HPV) infections, particularly certain combinations of types, have the tendency to cluster together. Cervical cell samples were collected from women in the framework of the IARC HPV Prevalence Surveys. Women with a cytology diagnosis of high-grade squamous intraepithelial lesion or worse were excluded, leaving 13,961 women for this analysis. HPV DNA was assessed using a general GP5+/6+ primer–mediated PCR. HPV genotyping was done using enzyme immunoassay or reverse line blot analysis. Logistic regression with type-specific HPV positivity as an outcome was used, adjusted for age, study area, and lifetime number of sexual partners. Woman-level random effects were added to represent unobservable risk factors common to all HPV types. The observed-to-expected ratio was 1.20 (95% credible interval, 1.14-1.26) for infection with two HPV types and 1.02 (95% credible interval, 0.91-1.12) for three for more types, with the best possible adjustment. Among combinations of specific HPV types, the tendency to cluster increased with the genetic similarity of the L1 region. High observed-to-expected ratios were found for closely homologous types, including HPV33/58, 18/45, 33/35, and 31/35. The excess of multiple infections, however, was clearly evident only when enzyme immunoassay, and not reverse line blot, was used as the genotyping method. The different results by genotyping method suggest that the apparent clustering of HPV infections was an artifact of the measurement process. Further investigation is required to evaluate other widely used HPV detection methods. Cancer Epidemiol Biomarkers Prev; 19(2); 503–10
Human Papillomavirus Types 16, 18, and 31 Serostatus and Prostate Cancer Risk in the Prostate Cancer Prevention Trial
Authors: Sutcliffe Siobhan , Viscidi Raphael P. , Till Cathee , Goodman Phyllis J. , Hoque Ashraful M. , Hsing Ann W. , Thompson Ian M. , Zenilman Jonathan M. , De Marzo Angelo M. , Platz Elizabeth A.
Published: February 2010

Since human papillomavirus (HPV) infection was first identified as a risk factor for cervical cancer, several seroepidemiologic and tissue-based studies have investigated HPV in relation to prostate cancer, another common genitourinary malignancy, with mixed results. To further inform this potential association, we conducted a large, prospective investigation of HPV types 16, 18, and 31 in relation to risk of prostate cancer in the Prostate Cancer Prevention Trial. Cases were a sample of men diagnosed with prostate cancer after visit 2 or on their end-of-study biopsy (n = 616). Controls were men not diagnosed with prostate cancer during the trial or on their end-of-study biopsy (n = 616). Controls were frequency matched to cases by age, treatment arm, and family history of prostate cancer. Sera from visit 2 were tested for IgG antibodies against HPV types 16, 18, and 31. No associations were observed for weak or strong HPV-16 [odds ratio (OR), 0.94; 95% confidence interval (95% CI), 0.53-1.64 and OR, 1.07; 95% CI, 077-1.48, respectively], HPV-18 (OR, 0.75; 95% CI, 0.27-2.04 and OR, 0.87; 95% CI, 0.47-1.63, respectively), or HPV-31 seropositivity (OR, 0.76; 95% CI, 0.45-1.28 and OR, 1.15; 95% CI, 0.80-1.64, respectively) and risk of prostate cancer. Considering this finding in the context of the HPV and prostate cancer literature, HPV does not appear to be associated with risk of prostate cancer, at least by mechanisms proposed to date, and using epidemiologic designs and laboratory techniques currently available. Cancer Epidemiol Biomarkers Prev; 19(2); 614–8
Colorectal Cancer Susceptibility Quantitative Trait Loci in Mice as a Novel Approach to Detect Low-Penetrance Variants in Humans: A Two-Stage Case-Control Study
Authors: Fernández-Rozadilla Ceres , Tarrío Rosa , Clofent Juan , de Castro Luisa , Brea-Fernández Alejandro , Bessa Xavier , Abulí Anna , Andreu Montserrat , Jover Rodrigo , Xicola Rosa , Llor Xavier , Castells Antoni , Castellví-Bel Sergi , Carracedo Angel , Ruiz-Ponte Clara ,   for the Gastrointestinal Oncology Group of the Spanish Gastroenterological Association
Published: February 2010

Thirty-five percent of colorectal cancer (CRC) susceptibility is thought to be attributable to genetics, but only a small proportion of the cases (<6%) can be explained by highly penetrant mutations. The rest of the susceptibility could be explained by a number of low-penetrance variants following a polygenic model of inheritance. Genetic modeling in rodents has been a successful tool for the unraveling of the genetic basis of diseases. The investigation of mouse quantitative trait loci led to the discovery of 15 “susceptibility to colorectal cancer” (Scc) loci. Thus, we aimed to analyze the human-mouse syntenic regions defined by these Scc loci and select human candidate genes within. Twenty-one genes were chosen and their single-nucleotide polymorphisms were tested as possible low-penetrance variants predisposing to CRC risk. Our most strongly associated single-nucleotide polymorphism, rs954353, seems to be in the 5′ region of the CYR61 gene, which could implicate it in terms of the cis-regulation of the gene. CYR61 has been proposed as a connection point among signaling pathways and a probable marker for early CRC detection. However, we could not replicate the association. Despite our negative results, we believe that our candidate gene selection strategy could be quite useful in the future determination of variants predisposing to disease. Cancer Epidemiol Biomarkers Prev; 19(2); 619–23