bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

AbstractEpidemiologic 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 &gt; 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

AbstractNo 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 &lt; 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 &lt; 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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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 &lt; 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

AbstractBackground: 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&gt;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&gt;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&gt;2 t/wk vs. &lt;1 t/wk, 0.56; 95% confidence interval, 0.28-1.13). We also detected interactions between NSAIDs and EP2 9814C&gt;A (intron 1) and PGDH 343C&gt;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

Abstract
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

Abstract
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