bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A10: Gene expression analysis of malignancy associated changes in normal bronchial epithelium
Authors: Thu Kelsie , Campbell Jennifer , Garnis Cathie , Coe Bradley , Lam Wan , MacAulay Calum , Lam Stephen 
Published: May 2012

Abstract
A10

Background
Lung cancer is the number one cancer-related cause of death in the world. The poor prognosis for lung cancer patients is largely due to the lack of an effective non-invasive method to detect the disease in its early stage. Using quantitative nuclear morphometry of sputum cells, we have previously demonstrated that in the presence of tumour, cytologically normal appearing diploid cells may exhibit malignancy-associated changes (MACs) and that these changes may be used as surrogate markers for early detection. The molecular basis for MACs is not known.

Objective
Our objective is to identify malignancy-associated gene expression changes in normal bronchial epithelial cells obtained by bronchial brushing.

Methods
We compared the pre- and post-surgical resection gene expression profiles of bronchial epithelial cells obtained by brushing of airways in the lung opposite to the one containing the lung cancer. Agilent whole genome expression arrays were used to generate mRNA transcript profiles for seven paired normal bronchial brushings taken before and 3 to 6 months after surgical resection of the tumour. Ingenuity Pathway Analysis software was used to identify downstream expression targets of the soluble signaling factors VEGF, TGF-β, TNF-α, and IL-8, which have been reported to be secreted by lung tumour cells. The target genes identified were analyzed for malignancy induced differential gene expression between normal bronchial epithelial cells from cancerous and non-cancerous environments.

Results
We detected differential expression of multiple target genes in the bronchial brush cells. Genes that were found to be differentially expressed included downstream targets of the signaling molecules EGF,TGF-β, and VEGF.

Conclusion
Soluble signaling molecules secreted by lung malignancies induce MACs, as evident by altered gene expression after removal of the tumour. Although further investigation is necessary, our results are consistent with previous observation that lung tumours can induce MACs in normal appearing bronchial cells in the vicinity of the tumor. MACs may be a potential marker for early detection of lung cancer. This data also provides evidence that MACs can be measured quantitatively in bronchial brush cells using gene expression analysis.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A10.
Abstract A103: Risk of breast cancer with plasma prolactin concentrations by phosphorylated STAT3 and STAT5 status
Authors: Tworoger Shelley , Rice Megan , Belsley Nichole , Walker Sarah , Collins Laura , Hankinson Susan , Frank David 
Published: May 2012

Abstract
A103
Prolactin, a lactogenic hormone, has been associated with risk of breast cancer in premenopausal and postmenopausal women. Prolactin may act by influencing transcription factors in the Signal Transducer and Activator of Transcription (STAT) pathway. In particular, STAT3 and STAT5 appear to be important in breast carcinogenesis; prolactin is known to activate STAT5 via phosphorylation. To determine whether prolactin may act through STAT signaling, we examined whether prediagnostic prolactin levels were differentially associated with risk of breast tumors based on their expression of phosphorylated STAT3 (pSTAT3) and STAT5 (pSTAT5). Tissue microarrays (TMAs) were constructed from 3,093 breast cancers from women enrolled in the Nurses Health Study. Of these, 443 cases had matching plasma prolactin levels drawn at diagnosis; one or two controls were matched to each case by age, menopausal status/hormone use, and characteristics of the blood draw. Immunohistochemical studies with pSTAT3 and pSTAT5 were performed on the TMAs. Tissue cores were scored from 0-3 based on intensity and quantity of nuclei staining. Relationships between expression of pSTAT3 or pSTAT5 and clinicopathologic features were examined by Chi-squared tests. Polytomous logistic regression was used to evaluate the relationship between prolactin and risk of breast tumors by staining expression, adjusting for matching factors and breast cancer risk factors. Interpretable tissue cores were available for 309 subjects. Of these, 195 (63%) and 114 tumors (37%) showed negative/weak (0-1) and moderate/strong staining (2-3) respectively for pSTAT3. 178 (58%) and 131 (42%) tumors showed negative/weak and moderate/strong staining respectively for pSTAT5. Absence of expression of pSTAT3 was significantly associated with high grade (p=0.04) and invasiveness (p=0.04). Though not statistically significant, pSTAT3- status also was associated with lymph node involvement and larger tumor size. pSTAT5 was not associated with other tumor characteristics. Prolactin levels were similarly associated with pSTAT3+ (RR, top vs. bottom quartile=1.7, 95% CI=1.1-2.8) and pSTAT3- tumors (comparable RR=1.8, 95%CI=1.0-3.3). However, high versus low prolactin levels were more strongly associated with pSTAT5+ tumors (RR=2.3, 95%CI=1.3-4.2) compared to pSTAT5- tumors (RR=1.5, 95%CI=0.9-2.4), although the p-heterogeneity was not statistically significant (p=0.28). Our findings suggest that prolactin may influence breast cancer risk via activation of STAT5. On-going analyses are exploring the combined role of pSTAT3 and pSTAT5 presence as well as other hormones thought to modulate or reflect STAT activity including IGFs, CRP, and adiponectin.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A103.
Abstract A106: Serum testosterone concentrations and risk of testicular germ cell tumors
Authors: Chia Victoria , Quraishi Sabah , Graubard Barry , Stanczyk Frank , Rubertone Mark , Erickson Ralph , McGlynn Katherine 
Published: May 2012

Abstract
A106
Although the incidence of testicular germ cell tumors (TGCT) has been rising worldwide, little known about the etiology. There is evidence, however, that TGCT is related to other male reproductive disorders, specifically, hypospadias, cryptorchidism and infertility. Because testosterone is responsible for the development and proliferation of testicular cells and testicular descent, it is plausible that testosterone and its binding protein, sex hormone binding globulin (SHBG), may be associated with TGCT risk. Using 512 case and 789 control participants from the U.S. Servicemen’s Testicular Tumor Environmental and Endocrine Determinants (STEED) Study, we assessed associations of pre-diagnostic serum SHBG and testosterone (measured total and calculated free) concentrations and risk of TGCT. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using adjusted logistic regression models. Among the controls, SHBG concentrations increased with age (p&lt;0.01), while free testosterone concentrations decreased with age (p=0.02). Total testosterone concentrations, however, were not associated with age (p=0.84). SHBG and total testosterone concentrations decreased with increasing body mass index (p&lt;0.01), however free testosterone did not (p=0.67). Overall, there were no statistically significant associations between SHBG and total testosterone concentrations and TGCT risk. There were suggestions that men had an increased risk of TGCT if they were in the highest quintile of SHBG (OR=1.41, 95% CI, 0.98-2.02) and free testosterone (OR=1.31, 95% CI, 0.91-1.88), but there were no statistically significant trends. Serum total testosterone concentrations were not associated with TGCT risk. There did not appear to be differences in risk by tumor subtype, seminoma versus nonseminoma, nor effect modification by body mass index. These results suggest that serum testosterone is not associated with risk of TGCT; other endogenous hormones, however, such as gonadotropins and estrogens, may provide additional clues to the etiology of TGCT.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A106.
Abstract A109: A prospective study of vitamin D receptor polymorphisms, interaction with vitamin D status, and colorectal cancer risk in men
Authors: Lee Jung Eun , Li Haojie , Giovannucci Edward , Hollis Bruce , Hunter David , Lee I-Min , Stampfer Meir , Ma Jing 
Published: May 2012

Abstract
A109
Growing evidence suggests an elevated risk of colorectal cancer among individuals with low levels of vitamin D, the biological actions of which is mediated by the vitamin D receptor (VDR). We examined the prospective associations between three VDR single nucleotide polymorphisms (SNPs) (BsmI (bb, bB/BB), FokI (FF, Ff/ff), and Cdx2 (G&gt;A)) and colorectal cancer risk and their interactions with plasma vitamin D status in a nested case-control study among men in the Physicians’ Health Study. A total of 249 incident colorectal cancer cases were identified through 2000 among men who provided blood specimens in 1982-1984 and individually matched to controls by age and smoking. We used conditional logistic regression to calculate the relative risk (RR) and 95% confidence interval (95% CI). We found that men with the VDR Cdx2 variant A allele tended to have a lower risk of developing colorectal cancer compared to men with the homozygous GG genotype (RR=0.71; 95% CI = 0.50-1.02; P = 0.06). Moreover, the lower risk of colorectal cancer associated with the VDR Cdx2 A genotype was mainly confined to men with low vitamin D status (plasma 25(OH)D below median level; RR = 0.45; 95% CI = 0.24-0.84; P = 0.03) but not among men with vitamin D levels above the median (P for interaction = 0.04). We found no statistically significant associations for the other two VDR SNPs, FokI or BsmI, or statistically significant interactions between plasma 25(OH)D levels and these two SNPs. Our prospective data suggest the hypothesis that the functional polymorphic Cdx2 A allele variation in the VDR gene, which is linked to a higher transcriptional activity of the VDR, may be protective against colorectal cancer development when vitamin D status is low.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A109.
Abstract A110: Kinase gene expression profiles are associated with clinical outcomes in clear cell renal cell carcinoma patients
Authors: Hildebrandt Michelle , Tamboli Pheroze , Huang Maosheng , Ye Yuanqing , Lee Ju-Seog , Wu Xifeng 
Published: May 2012

Abstract
A110
There are 516 known kinases in the human genome. These proteins are involved in regulating nearly all cellular processes through phosphorylation of target proteins. Because of their important role maintaining proper cellular function, they are often misregulated during tumorigenesis and associated with clinical outcomes in cancer patients. Similarly to other cancers, several kinases have been found to play key roles during development of renal cell carcinoma (RCC). However, less is known about the global expression status of these genes in RCC and their association with clinical outcomes. To identify variation in the RCC kinome, we performed a systematic analysis of gene expression for 503 human kinases using Illumina whole genome arrays in 93 tumor samples. Expression levels were analyzed with regard to associations with recurrence and overall survival. Six kinases were found to be significantly associated with an increased risk developing a recurrence, while two kinases were protective (p &lt; 0.01). Furthermore, an expression signature comprised of these eight genes was able to identify low risk and high risk groups of patients (HR: 26.83, 95% CI: 3.77-190.78, p = 0.0010). These two risk groups also had significantly different recurrence-free survival times of 67.6 compared to 37.9 months (p = 0.0003) for the low and high risk groups, respectively. Expression of one of these eight genes, IKBKE, was also associated with a 5.3-fold increased risk of dying (95% CI: 1.93-14.59, p = 0.0012). Interestingly, this kinase was constantly associated with a poor prognosis in both univariable and multivariable analyses with similar HRs, indicating that expression levels of this gene may be a candidate, independent prognostic marker for RCC. IKBKE is a member of the NFκB signaling pathway and is responsible for regulation of NFκB-mediated transcriptional activation of genes involved in inflammation, immunity and stress responses. Overall, these results suggest a major role of global kinase gene expression in modulating clinical outcomes in RCC patients while identifying several candidate genes, including IKBKE, for further study.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A110.
Abstract A111: Genetic variations in five estrogen metabolizing genes and endometrial cancer risk
Authors: Yang Hannah , Platz Elizabeth , Gaudet Mia , Lacey James , Brinton Louise , Lissowska Jolanta , Peplonska Beata , Sherman Mark , Chanock Stephen , Garcia-Closas Montserrat 
Published: May 2012

Abstract
A111

BACKGROUND
Estrogen plays a major role in endometrial carcinogenesis and the balance of estrogen metabolites has been hypothesized to be a determinant of risk. Cytochrome p450 (CYP) enzymes, CYP1A1, CYP1A2, and CYP3A4 catalyze the 2-OHE1 pathway, whereas the CYP1B1 catalyzes the 4-OHE1 pathway. The activity of these enzymes determines the proportion of metabolites and a higher proportion of the 4-OHE1 metabolites is thought to have a higher carcinogenic potential. Although several studies have examined the association between single nucleotide polymorphisms (SNPs) of these estrogen metabolizing genes and endometrial cancer risk, results have been inconsistent and limited to putatively functional variants.

METHODS
We comprehensively assessed known common genetic variation in these estrogen metabolizing genes by genotyping candidate and tagging SNPs (tagSNPs) in a population-based case-control study of 417 endometrial cancer cases and 407 controls (most of whom were postmenopausal) conducted in Poland (Warsaw and Lodz) between 2001-2003. The following criteria were used to identify tagSNPs: (1) located in the respective gene or within the 5kb flanking regions, (2) with a minor allele frequency greater than or equal to 0.01 in Caucasian populations, and (3) with pairwise r2=0.90 between tagSNPs and undetermined SNPs. A total of 5 SNPs for CYP1A1, 7 for CYP1A2, 9 for CYP1A1/A2, 34 for CYP1B1, 6 for CYP3A4, and 12 for COMT were examined. Genotyping was performed using an Illumina Custom Infinium iSelect assay that included nearly 27,000 SNPs with coverage of over 1,300 candidate genes.

RESULTS
We did not observe significant associations for candidate variants of CYP1A1 (rs1048943 (I462V) per C allele: OR (95% CI)=0.98 (0.56-1.72); rs1799814 (T461N) per T allele: 1.75 (0.94-3.24)); CYP1A2 (rs762551 (IVS1-154C&gt;A) per C allele:0.91(0.74-1.12)); CYP1B1 (rs1056827 (A119S) per A allele: 0.98 (0.80-1.20); rs1056836 (V432L) per C allele: 0.96 (0.79-1.18); rs1800440 (N453S) per C allele: 1.15 (0.88-1.51)); and CYP3A4 (rs2740574 (-391A&gt;G) per C allele: 1.46 (0.84-2.54)). In addition, we did not observe any significant association with endometrial cancer risk in haplotype analyses (global p-value&gt;0.3) or the individual tagSNPs analyses (p-trend&gt;0.09). Meta-analysis including our study and previous reports for these SNPs did not show significant overall associations; however, there is substantial heterogeneity across studies.

DISCUSSION
Our findings do not provide evidence for a substantial association between common genetic variation of estrogen metabolizing genes with endometrial cancer risk. However weak associations with these genes or association with other genes in the estrogen metabolizing pathway may exist.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A111.
Abstract A114: No increased risk of cancer after coal tar treatment in patients with psoriasis or eczema
Authors: Roelofzen Judith , Aben Katja , Oldenhof Ursula , Coenraads Pieter-Jan , Alkemade Hans , Van de Kerkhof Peter , Van der Valk Pieter , Kiemeney Lambertus 
Published: May 2012

Abstract
A114

Background
Coal tar is an effective topical treatment for psoriasis and eczema, but it contains several carcinogenic polycyclic aromatic hydrocarbons (PAHs), such as benzo(a)pyrene, benz(a)antracene and dibenz(a,h)anthracene. Occupational and animal studies showed an increased risk of cancer after exposure to coal tar. Many dermatologists have abandoned this effective treatment for safety reasons, although the risk of cancer after dermatological coal tar therapy is unclear. To study the risk of cancer after coal tar treatment and other therapies, the LATER study (Late effects of coal tar treatment in eczema and psoriasis; the Radboud study) was conducted.

Methods
A large historical cohort study was performed including 13,200 patients diagnosed with psoriasis and eczema between 1960 and 1990 at three large hospitals in the Netherlands. Specific information on skin disease and treatment, risk factors and cancer occurrence was retrieved from medical files, postal questionnaires, the Netherlands Cancer Registry and Causes of Death Registry. Cox Proportional Hazard regression models were used to evaluate differences in cancer risk by treatment modality.

Results
Coal tar treatment did not increase the risk of non-skin malignancies (HR=0.92; 95%CI=0.78-1.09), nor the risk of skin cancer (excluding basal cell carcinoma) (HR=1.09; 95%CI=0.69-1.72). Alternative therapies, such as PUVA and systemic therapies appeared to be associated with an increased risk of skin cancer (HR=1.17; 95%CI=0.75-1.82 and HR=2.33; 95%CI=1.60-3.40, respectively), but no increased risk of non-skin cancer was observed (HR=0.91; 95%CI=0.75-1.10 and HR=1.12; 95%CI=0.95-1.32).

Conclusion
This study is the first study with sufficient numbers of patients and follow-up to reliably estimate the risk of cancer after coal tar treatment. The use of coal tar was not associated with an increased risk of cancer. PUVA and systemic therapies showed an increased risk of skin cancer, but no increased risk of tumours at other sites was observed. After considering the risks and benefits of coal treatment against the risks and benefits of other therapies, we conclude that coal tar coal tar can be maintained as a safe and effective treatment within dermatological practice.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A114.
Abstract A12: Increased expression of STEAP1 gene as potential poor prognostic marker of prostate cancer
Authors: Ihlaseh Shadia , Gambarini Greicy , Trindade Jose Carlos , Domingues Maria , Rogatto Silvia , de Camargo Joao Lauro 
Published: May 2012

Abstract
A12
Prostate cancer is a public health problem due to its high incidence and mortality rates. STEAP1 and STEAP2 genes (six-transmembrane epithelial antigen of prostate 1 e 2) are mapped at 7q21.13 region, where we have previously described genomic gains by array comparative genomic hybridization (aCGH) of primary prostate adenocarcinomas (PCa). The involvement of these genes in PCa development and progression remains to be clarified. They express tumor antigens and are putative molecular markers. The objective of this study was to determine STEAP1 and STEAP2 genes expressions by real time quantitative PCR (qPCR) and STEAP1protein expression by immunohistochemistry in samples of PCa, in surrounding non-neoplastic tissues, and in prostate nodular hyperplasia. Patients were classified in three groups of recurrence risk depending on serum PSA levels, Gleason scores, and tumor stages for qPCR analysis. Increased STEAP1 and STEAP2 genes expressions were registered in 16% and 21% of the 55 samples, respectively; both genes presented simultaneous increased expression in three high-risk cases. Similar pattern of expression of these genes were detected in the majority of PCa and in surrounding non-neoplastic tissues. Compared to surrounding non-neoplastic tissues, there was significant increase of STEAP1 expression in tumor samples with Gleason scores ≥ 7(4+3) and in cases with vascular invasion. There was a trend for increased STEAP1 expression in high-risk cases when compared to the moderate-risk group. In accordance with gene expression, higher levels of STEAP1 protein were expressed in PCa compared to surrounding non-neoplastic tissues. Our data suggest that increased STEAP1 expression is related to clinical and pathological parameters of PCa patients and it use as a poor prognostic marker should be considered.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A12.
Abstract A120: Agricultural pesticide use and pancreatic cancer risk in the agricultural health study cohort
Authors: Andreotti Gabriella , Beane Freeman Laura , Hou Lifang , Coble Joseph , Rusiecki Jennifer , Hoppin Jane , Silverman Debra , Alavanja Michael 
Published: May 2012

Abstract
A120
Pancreatic cancer is a rapidly fatal disease that has been linked with pesticide use. Previous studies have reported excess risks of pancreatic cancer with organochlorines such as DDT, however, many other commonly used pesticides have not been examined. To further examine the potential associations between the use of a number of pesticides and pancreatic cancer, we conducted a case-control analysis in the Agricultural Health Study, one of the largest prospective cohorts with over 89,000 participants including pesticide applicators and their spouses in Iowa and North Carolina. This analysis included 93 incident pancreatic cancer cases (64 applicators, 29 spouses) and 82,503 cancer-free controls who completed an enrollment questionnaire providing detailed pesticide use, demographic and lifestyle information.Ever use of 24 pesticides and intensity-weighted lifetime days [(lifetime exposure days) x (exposure intensity score)] of 13 pesticides was assessed. Risk estimates were calculated using unconditional logistic regression controlling for age, smoking, and diabetes. Among pesticide applicators, two herbicides (EPTC and pendimethalin) of the 13 pesticides examined for intensity-weighted lifetime use showed a statistically significant exposure-response association with pancreatic cancer. Applicators in the top half of lifetime pendimethalin use had a 3.0-fold (95% CI 1.3-7.2, p-trend=0.01) risk compared to never users, and those in the top half of lifetime EPTC use had a 2.56-fold (95% CI=1.1-5.4, p-trend=0.01) risk compared to never users. Organochlorines were not associated with an excess risk of pancreatic cancer in this study. These findings suggest that herbicides, particularly pendimethalin and EPTC, may be associated with pancreatic cancer.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A120.