bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polymorphisms in Mitochondrial Genes and Prostate Cancer Risk
Authors: Wang Liang , McDonnell Shannon K. , Hebbring Scott J. , Cunningham Julie M. , St Sauver Jennifer , Cerhan James R. , Isaya Grazia , Schaid Daniel J. , Thibodeau Stephen N. 
Published: December 2008

Abstract
The mitochondrion, conventionally thought to be an organelle specific to energy metabolism, is in fact multifunctional and implicated in many diseases, including cancer. To evaluate whether mitochondria-related genes are associated with increased risk for prostate cancer, we genotyped 24 single-nucleotide polymorphisms (SNP) within the mitochondrial genome and 376 tagSNPs localized to 78 nuclear-encoded mitochondrial genes. The tagSNPs were selected to achieve ≥80% coverage based on linkage disequilibrium. We compared allele and haplotype frequencies in ∼1,000 prostate cancer cases with ∼500 population controls. An association with prostate cancer was not detected for any of the SNPs within the mitochondrial genome individually or for 10 mitochondrial common haplotypes when evaluated using a global score statistic. For the nuclear-encoded genes, none of the tagSNPs were significantly associated with prostate cancer after adjusting for multiple testing. Nonetheless, we evaluated unadjusted P values by comparing our results with those from the Cancer Genetic Markers of Susceptibility (CGEMS) phase I data set. Seven tagSNPs had unadjusted P ≤ 0.05 in both our data and in CGEMS (two SNPs were identical and five were in strong linkage disequilibrium with CGEMS SNPs). These seven SNPs (rs17184211, rs4147684, rs4233367, rs2070902, rs3829037, rs7830235, and rs1203213) are located in genes MTRR, NDUFA9, NDUFS2, NDUFB9, and COX7A2, respectively. Five of the seven SNPs were further included in the CGEMS phase II study; however, none of the findings for these were replicated. Overall, these results suggest that polymorphisms in the mitochondrial genome and those in the nuclear-encoded mitochondrial genes evaluated are not substantial risk factors for prostate cancer. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3558–66)
Methylation Array Analysis of Preoperative and Postoperative Saliva DNA in Oral Cancer Patients
Authors: Viet Chi T. , Schmidt Brian L. 
Published: December 2008

AbstractPurpose: To perform methylation array analysis of 807 cancer-associated genes using tissue and saliva of oral squamous cell carcinoma (OSCC) patients with the objective of identifying highly methylated gene loci that hold diagnostic and predictive value as a biomarker.Experimental Design: We did the methylation array on DNA extracted from preoperative saliva, postoperative saliva, and tissue of 13 patients with OSCC, and saliva of 10 normal subjects. We identified sites that were highly methylated in the tissue and preoperative saliva samples but not methylated in the postoperative saliva samples or in normal subjects.Results: High quality DNA was obtained and the methylation array was successfully run on all samples. We identified significant differences in methylation patterns between the preoperative and postoperative saliva from cancer patients. We established a gene classifier consisting of 41 gene loci from 34 genes that showed methylation in preoperative saliva and tissue but were not methylated in postoperative saliva or normal subjects. Gene panels of 4 to 10 genes were constructed from genes in the classifier. The panels had a sensitivity of 62% to 77% and a specificity of 83% to 100% for OSCC.Conclusions: We report methylation array analysis of 807 cancer-associated genes in the saliva of oral cancer patients before and after oral cancer resection. Our methylation biomarker approach shows the proof of principle that methylation array analysis of saliva can produce a set of cancer-related genes that are specific and can be used as a composite biomarker for the early detection of oral cancer. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3603–11)
Effect of Insulin-Like Growth Factor Gene Polymorphisms Alone or In Interaction with Diabetes on the Risk of Pancreatic Cancer
Authors: Suzuki Hideo , Li Yanan , Dong Xiaoqun , Hassan Manal M. , Abbruzzese James L. , Li Donghui 
Published: December 2008

AbstractInsulin-like growth factors (IGF) have been associated with risk of common human cancers, but the association between IGFs and pancreatic cancer risk is unclear. To determine whether genetic variations of IGF modify pancreatic cancer risk, we compared the frequency of six single nucleotide polymorphisms of IGF1 and IGF2 in a large-scale case control study. Single nucleotide polymorphisms were investigated using the TaqMan method in 892 patients with pancreatic ductal adenocarcinoma and 783 healthy controls who were recruited from The University of Texas M. D. Anderson Cancer Center from 2000 to 2007. Cases and controls were frequency matched by age (±5 years), race, and sex. Risk factor information was collected using direct interviews. We estimated odds ratios (OR) and 95% confidence intervals (95% CI) using unconditional multivariate logistic regression models. A haplotype of IGF1 gene containing the 3′-UTR Ex4 -177 G&gt;C G allele had a significantly lower frequency in cases (0.027) than in controls (0.041; P = 0.039). A statistically significant joint effect of the IGF1 3′-UTR Ex4 -177 G&gt;C C allele and diabetes on pancreatic cancer risk was observed. The OR (95% CI) were 1.07 (0.81-1.42), 2.12 (1.53-2.93), and 5.69 (2.63-12.3) for individuals who had the CC/CG genotype alone, diabetes alone, or both factors, respectively, compared with subjects without either of the two factors with adjustment for other risk factors. The IGF2 3′-UTR Ex4 -233C&gt;T TT genotype was significantly associated with a reduced risk of pancreatic cancer (OR = 0.07; 95% CI = 0.01-0.57; P = 0.013). The polymorphic variants of the IGF genes may serve as a susceptibility factor for pancreatic cancer. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3467–73)
Triple-Negative Breast Cancer and Obesity in a Rural Appalachian Population
Authors: Vona-Davis Linda , Rose David P. , Hazard Hannah , Howard-McNatt Marissa , Adkins Farrell , Partin Jessica , Hobbs Gerald 
Published: December 2008

Abstract
Background: Our objective was to determine the clinicopathologic features of triple-negative (estrogen receptor, progesterone receptor, and human epidermal growth factor-2 receptor negative) breast cancer and their relationship to obesity in women drawn from a population with one of the highest obesity rates in the United States.
Methods: This retrospective study involved 620 White patients with invasive breast cancer in West Virginia. Hospital tumor registry, charts, and pathology records provided age at diagnosis, tumor histologic type, size, nodal status, and receptor status. Body mass index was calculated and a value of ≥30 was considered indicative of obesity.
Results: Triple-negative tumors occurred in 117 (18.9%) of the 620 patients, most often in association with invasive ductal carcinomas. Patients with triple-negative tumors were younger than those with other receptor types, 44.5% and 26.7%, respectively, being diagnosed at age &lt;50 years (P = 0.0004). The triple-negative tumors were larger (P = 0.0003), most notably in the younger women, but small tumors (&lt;2.0 cm) were more often accompanied by lymph node metastases. Obesity was present in 49.6% of those with triple-negative tumors but in only 35.8% of those with non-triple-negative tumors (P = 0.0098). Lymph node metastases were more frequently associated with T2 tumors in obese patients (P = 0.032) regardless of their receptor status.
Conclusions: Triple-negative breast cancers within a White, socioeconomically deprived, population occurred in younger women, with later stage at diagnosis, and in association with obesity, which itself has been associated with a poor prognosis in breast cancer. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3319–24)
Human Papillomavirus-16 Modifies the Association between Fruit Consumption and Head and Neck Squamous Cell Carcinoma
Authors: Meyer Mara S. , Applebaum Katie M. , Furniss C. Sloane , Peters Edward S. , Luckett Brian G. , Smith Judith F. , Bryan Janine , McClean Michael D. , Marsit Carmen , Kelsey Karl T. 
Published: December 2008

AbstractHuman papillomavirus-16 (HPV-16) is a risk factor for head and neck squamous cell carcinoma (HNSCC). HPV-positive cancers have distinct disease cofactors and improved survival following treatment. There is conflicting evidence of a protective association of fruit consumption with HNSCC. As HPV-related disease is clinically distinct, we investigated whether the association between fruit consumption and HNSCC risk was modified by exposure to HPV-16. We studied 270 cases and 493 controls with fruit intake information and known HPV-16 antibody status. Cases were identified at nine Boston-area medical facilities between 1999 and 2003. Controls were randomly selected from the greater population and frequency matched to cases by age, gender, and town of residence. Controlling for age, gender, race, smoking, alcohol, total energy intake, body mass index, and education, the seronegative individuals had a significantly lower risk of HNSCC with increasing total fruit consumption [odds ratio (OR)tertile 2, 0.60; 95% confidence interval (95% CI), 0.38-0.95; ORtertile 3, 0.57; 95% CI, 0.35-0.95] and specifically increasing citrus fruit consumption (ORtertile 2, 0.61; 95% CI, 0.39-0.97; ORtertile 3, 0.59; 95% CI, 0.37-0.96). However, among the seropositive, risk increased with greater fruit consumption (ORtertile 2, 2.27; 95% CI, 0.92-5.58; ORtertile 3, 1.40; 95% CI, 0.55-3.59) and citrus fruit consumption (ORtertile 2, 3.35; 95% CI, 1.36, 8.24; ORtertile 3, 3.15; 95% CI, 1.23-8.08). This interaction was statistically significant (P &lt; 0.05), showing that fruit consumption was associated with a reduced HNSCC risk among HPV-16-seronegative individuals but an increased HNSCC risk among the HPV-16-seropositive individuals. These findings suggest that dietary factors dramatically alter the pattern of occurrence of HPV-associated HNSCC and show that viral-related disease is clinically and etiologically distinct. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3419–26)
Nicotinic Receptor Gene Variants Influence Susceptibility to Heavy Smoking
Authors: Stevens Victoria L. , Bierut Laura J. , Talbot Jeffrey T. , Wang Jen C. , Sun Juzhong , Hinrichs Anthony L. , Thun Michael J. , Goate Alison , Calle Eugenia E. 
Published: December 2008

Abstract
Heavy smoking is a strong predictor of nicotine dependence, which is a major impediment to smoking cessation. Although both heavy smoking and nicotine dependence are highly heritable, previous attempts to identify genes influencing these phenotypes have been largely unsuccessful until very recently. We studied 1,452 heavy smokers (defined as smoking at least 30 cigarettes per day for at least 5 years) and 1,395 light smokers (defined as smoking &lt;5 cigarettes per day for at least 1 year) to investigate the association of common variants in nicotinic receptor subunit genes with smoking behavior. Compared with the most common allele, two separate groups of single nucleotide polymorphisms (SNP) in the CHRNA5-CHRNA3-CHRNB4 gene cluster were associated with heavy smoking with a very high statistical significance. One group of eight SNPs, which included a nonsynonymous SNP in the CHRNA5 gene, was in strong linkage disequilibrium and associated with increased risk of heavy smoking. A second group of SNPs not strongly correlated with the first was associated with decreased risk of heavy smoking. Analyses that combined both groups of SNPs found associations with heavy smoking that varied by &gt;2-fold. Our findings identify two loci in the CHRNA5-CHRNA3-CHRNB4 gene cluster that predict smoking behavior and provide strong evidence for the involvement of the α5 nicotinic receptor in heavy smoking. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3517–25)
Missense Polymorphisms in Matrix Metalloproteinase Genes and Skin Cancer Risk
Authors: Nan Hongmei , Niu Tianhua , Hunter David J. , Han Jiali 
Published: December 2008

Abstract
Matrix metalloproteinases (MMP) degrade various components of the extracellular matrix, and their overexpression has been implicated in tumor progression. Nonsynonymous single nucleotide polymorphisms (SNPs) lead to amino acid substitutions that can alter the function of the encoded protein. We evaluated the associations of six nonsynonymous SNPs in the MMP3, MMP8, and MMP9 genes with skin cancer risk in a nested case-control study of Caucasians within the Nurses' Health Study among 218 melanoma cases, 285 squamous cell carcinoma (SCC) cases, 300 basal cell carcinoma (BCC) cases, and 870 normal controls. We observed that the MMP9 Arg668Gln polymorphism was significantly associated with a decreased risk of SCC. Compared with the Arg/Arg group, the multivariate odds ratio was 0.67 (95% confidence interval, 0.47-0.97) for the Arg/Gln group and 0.21 (95% confidence interval, 0.05-0.97) for the Gln/Gln group (Ptrend = 0.004). We did not observe any association of this SNP with the risks of melanoma and basal cell carcinoma. No associations were found for other SNPs with skin cancer risk. This study provides evidence for the contribution of the MMP9 Arg668Gln to SCC development. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3551–7)
No Association between Common Chemokine and Chemokine Receptor Gene Variants and Prostate Cancer Risk
Authors: Petersen Desiree C. , Severi Gianluca , Hoang Hoa N. , Padilla Emma J.D. , Southey Melissa C. , English Dallas R. , Hopper John L. , Giles Graham G. , Hayes Vanessa M. 
Published: December 2008

Abstract
There is growing evidence that inflammation and infection play important roles in the etiology of prostate cancer. As the chemokine network is directly involved in inflammation and infectious diseases, we tested for an association between six common putative functional variants and prostate cancer risk using an Australian case-control study. We measured CCL5 −403G&gt;A, CXCL12 +801G&gt;A, CCR2V64I (G&gt;A), CCR5Δ32, CX3CR1V249I (G&gt;A), and CX3CR1T280M (C&gt;T) for 815 cases and 738 controls. Of these, only CXCL12 +801G&gt;A has previously been tested and found to be associated with prostate cancer risk. We found no significant associations with prostate cancer risk (all P &gt; 0.4). All per allele odds ratios ranged from 0.96 (95% confidence intervals, 0.80-1.16) to 1.06 (95% confidence intervals, 0.90-1.23). This suggests that these common chemokine and chemokine receptor variants do not play a major, if any, role in susceptibility to prostate cancer. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3615–7)
Delphinidin Attenuates Neoplastic Transformation in JB6 Cl41 Mouse Epidermal Cells by Blocking Raf/Mitogen-Activated Protein Kinase Kinase/Extracellular Signal-Regulated Kinase Signaling
Authors: Kang Nam Joo , Lee Ki Won , Kwon Jung Yeon , Hwang Mun Kyung , Rogozin Evgeny A. , Heo Yong-Seok , Bode Ann M. , Lee Hyong Joo , Dong Zigang 
Published: December 2008

Abstract
Recent studies suggest that anthocyanidins play a pivotal role in the chemopreventive effects of fruits and vegetables. However, the underlying molecular mechanisms and cellular targets remain unknown. Neoplastic transformation of cells and inflammation are considered to be major events contributing to carcinogenesis. Here, we report that delphinidin, a major dietary anthocyanidin, inhibits tumor promoter–induced transformation and cyclooxygenase-2 (COX-2) expression in JB6 promotion-sensitive mouse skin epidermal (JB6 P+) cells by directly targeting Raf and mitogen-activated protein kinase kinase (MEK). Delphinidin inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)–induced neoplastic transformation and COX-2 expression at both the protein and transcriptional levels. The activation of activator protein-1 and nuclear factor-κB induced by TPA was dose dependently inhibited by delphinidin treatment. Delphinidin strongly suppressed Raf1 and MEK1 kinase activities and subsequently attenuated TPA-induced phosphorylation of MEK, extracellular signal-regulated kinase (ERK), p90RSK, and MSK. Although delphinidin suppressed ERK and c-Jun NH2-terminal kinase activities, it was more effective at inhibiting Raf1 or MEK1 activities. Pull-down and competition assays revealed that delphinidin binds with Raf1 or MEK1 noncompetitively with ATP. Delphinidin also dose dependently suppressed JB6 P+ cell transformation induced by epidermal growth factor and H-Ras, both of which are involved in the activation of Raf/MEK/ERK signaling. Together, these findings suggested that the targeted inhibition of Raf1 and MEK activities and COX-2 expression by delphinidin contribute to the chemopreventive potential of fruits and vegetables.
Identification of Mucin Depleted Foci in the Human Colon
Authors: Femia Angelo Pietro , Giannini Augusto , Fazi Marilena , Tarquini Elena , Salvadori Maddalena , Roncucci Luca , Tonelli Francesco , Dolara Piero , Caderni Giovanna 
Published: December 2008

Abstract
Aberrant crypt foci (ACF) originally described in rodents treated with colon-specific carcinogens have been identified also in humans at high risk of colon cancer (CRC) and are extensively used as cancer biomarkers. However, studies documenting the heterogeneity of ACF have questioned their precancerous nature. Recently, we described dysplastic foci depleted of mucins (MDF) in the colon of rats treated with colon-specific carcinogens. Like colon tumors, MDFs show activation of Wnt signaling driven by mutations in the β-catenin gene and Apc, a key gene in colorectal carcinogenesis. Because MDFs have been identified thus far only in rodents, we wanted to search for similar lesions in humans. Familial adenomatous polyposis (FAP) subjects, carrying germ-line mutations in the APC gene, are at high risk of CRC. Therefore, we first searched for MDF-like lesions in unsectioned colon samples from FAP patients and then in patients with sporadic CRC. MDFs were present in the colon of FAP patients (average of 0.0577 lesions/cm2) and at a much lower density in CRC patients (average of 0.0006 lesions/cm2). ACFs were also observed in all patients. Histologic preparations of all the MDFs identified in FAP and CRC consisted of microadenomas at variable grades of dysplasia. The occurrence of MDF-like lesions in high-risk patients provides evidence that these lesions have a counterpart in human pathology and, as observed in rodents, may represent the very early stages of CRC.
A Novel Derivative of the Natural Agent Deguelin for Cancer Chemoprevention and Therapy
Authors: Kim Woo-Young , Chang Dong Jo , Hennessy Bryan , Kang Hae Jin , Yoo Jakyung , Han Seung-Ho , Kim Yoo-Shin , Park Hyun-Ju , Geo Seung-Yong , Mills Gordon , Kim Kyu-Won , Hong Waun Ki , Suh Young-Ger , Lee Ho-Young 
Published: December 2008

Abstract
The natural compound deguelin has promising preventive and therapeutic activity against diverse cancers by directly binding to heat shock protein-90 and thus suppressing its function. Potential side effects of deguelin over a certain dose, however, could be a substantial obstacle to its clinical use. To develop a derivative(s) of deguelin with reduced potential side effects, we synthesized five deguelin analogues (SH-02, SH-03, SH-09, SH-14, and SH-15) and compared them with the parent compound and each other for structural and biochemical features; solubility; and antiproliferative effects on normal, premalignant, and malignant human bronchial epithelial (HBE) and non–small-cell lung cancer (NSCLC) cell lines. Four derivatives destabilized hypoxia-inducible factor-1α as potently as did deguelin. Reverse-phase protein array (RPPA) analysis in H460 NSCLC cells revealed that deguelin and the derivatives suppressed expression of a number of proteins including heat shock protein-90 clients and proteins involved in the phosphoinositide 3-kinase/Akt pathway. One derivative, SH-14, showed several features of potential superiority for clinical use: the highest apoptotic activity; no detectable influence on Src/signal transducer and activator of transcription signaling, which can promote cancer progression and is closely related to pathogenesis of Parkinson's disease (deguelin, SH-02 and SH-03 strongly activated this signaling); better aqueous solubility; and less cytotoxicity to immortalized HBE cells (versus deguelin) at a dose (1 μmol/L) that induced apoptotic activity in most premalignant and malignant HBE and NSCLC cell lines. These collective results suggest that the novel derivative SH-14 has strong potential for cancer chemoprevention and therapy, with equivalent efficacy and lesser toxicity (versus deguelin).
Model Representation of Local Air Quality Characteristics
Authors: Mueller Stephen F. 
Published: December 2008

Abstract
Daily (24 h) and hourly air quality data at several sites are used to examine the performance of the fifth-generation Pennsylvania State University–NCAR Mesoscale Model (MM5)–Community Multiscale Air Quality Model (CMAQ) system over a 3-month period in 2003. A coarse (36 km) model grid was expected to provide relatively poor performance for ozone and comparatively better performance for fine particles, especially the more regional sulfate and carbonaceous aerosols. However, results were different from this expectation. Modeling showed significant skill for ozone at several locations but very little skill for particulate species. Modeling did poorly identifying surface wind directions associated with the highest and lowest pollutant exposures at most sites, although results varied widely by location. Model skill appeared to be better for ozone when spatial–temporal (S–T) patterns were examined, due in part to the ability of the model to reproduce much of the temporal variance associated with the diurnal photochemical cycle. At some sites the modeling even performed well in replicating the directional variability of hourly ozone despite relatively low spatial resolution. MM5–CMAQ spatial (directional) representation of 24-h-average particulate data was not good in most cases, but model skill improved somewhat when hourly data were examined. Modeling exhibited skill for sulfate at only one of nine sites using 24-h data averaged by daily resultant wind direction, at two of six sites when hourly data were averaged by direction, and at four of six sites when the combined spatial and temporal variance of sulfate was examined. Results were generally poorer for total carbon aerosol mass and total mass of particulate matter with diameter of less than 2.5 μm (PM2.5). The primary result of this study is that an S–T analysis of pollutant patterns reveals model performance insights that cannot be realized by only examining model error statistics as is typically done for regulatory applications. Use of this S–T analysis technique is recommended for better understanding model performance during longer simulation periods, especially when using grids of finer spatial resolution for applications supporting local air quality management studies. Of course, using this approach will require measuring semicontinuous fine particle data at more sites and for longer periods.