bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A107: Variation in the prolactin and prolactin receptor genes and familial breast cancer
Authors: Hussain Shehnaz K. , Sehl Mary , Conn Daniel , Sinsheimer Janet S. , Dandekar Uma , Papp Jeanette , Zhang Zuo-Feng , Ganz Patricia A. 
Published: January 2014

Abstract
Background: Breast cancer aggregates within some families, accounting for about 25% of incident cases. Known genetic variants, such as BRCA1/BRCA2 mutations, account for less than 10% of these familial breast cancer cases, thus, research into additional risk or protective genetic factors for familial breast cancer may provide valuable information for risk stratification. Serum levels of prolactin have been associated with sporadic breast cancer risk in previous studies. We sought to test the hypothesis that variation in the genes coding for prolactin (PRL) and the prolactin receptor (PRLR) would be associated with increased or decreased risk of familial breast cancer.
Methods: We designed a case-control study of probands recruited between 1998 and 2009 by the UCLA Family Cancer Registry; a population enriched with women having a strong family history of breast cancer and BRCA1/BRCA2 mutation carriers. Genotyping of tagSNPs in PRL (n=11) and PRLR (n=28) was performed in 351 unrelated women who developed breast cancer and 290 unaffected controls with similar family histories to the cases. Multivariate logistic regression models controlling for age, Ashkenazi Jewish heritage, education, and number of affected relatives were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between SNPs and familial breast cancer. Genotype specific ORs as well as per-allele (additive model) ORs were calculated.
Results: Familial breast cancer risk was inversely associated with carriership of the minor alleles for three PRLR SNPs in the additive models, rs9292573 (OR=0.7, 95% CI=0.5-0.9), rs10805603 (OR=0.6, 95% CI=0.4-0.9), and rs1587607 (OR=0.7, 95% CI=0.5-1.0). PRLR SNP rs249522 was associated with increased risk of cancer in the additive model (OR=1.8, 95% CI =1.2-2.7). Minor allele carriers of the PRL SNP rs12210179, located in a putative transcription factor binding site, had a decreased risk of cancer in the additive model (OR=0.7, 95% CI=0.5-0.9).
Conclusion: These data suggest that genetic variation in PRL and PRLR are associated with breast cancer in a population with a strong family history of breast cancer.
Citation Format: Shehnaz K. Hussain, Mary Sehl, Daniel Conn, Janet S. Sinsheimer, Uma Dandekar, Jeanette Papp, Zuo-Feng Zhang, Patricia A. Ganz. Variation in the prolactin and prolactin receptor genes and familial breast cancer. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A107.
Abstract A16: Genetic polymorphisms in the carcinogen metabolism pathway and lung cancer risk
Authors: Dalay Nejat , Buyru Nur , Yalniz Zubeyde 
Published: January 2014

Abstract
Alterations affecting genes involved in the carcinogen metabolism are associated with cancer susceptibility since these can affect the detoxification capacity of the gene product. Genes regulating the carcinogen metabolism are also highly effective in the pathways involved in lung cancer development. The microsomal epoxide hydroxylase gene EPHX1 participates in the detoxification and activation of the carcinogenic compounds in the cigarette smoke. Two polymorphic changes in the EPHX1 gene result in slow and fast alleles with low and high enzyme activity. This differential effect suggests that these polymorphisms may affect individual lung cancer risk.
Myeloperoxidase (MPO) is an oxidative enzyme released in response to cigarette smoke from the lung tissue. A G&gt;A polymorphism located in the 5' untranslated region of the MPO gene that may be responsible for reduced transcriptional activity due to the decreased binding affinity for the SP1 transcription factor. In individuals carrying the A allele metabolic procarcinogen compounds are not effectively activated. Therefore, this variant is thought to play a protective role in lung cancer.
The NAD(P)H dehydrogenase (NQO1) gene is an important mediator of lung cancer and codes for a cytoplasmic electron reductase which prevents the production of reactive radical species by detoxification of the quinones and their derivatives. Mutations in the NQO1 gene have been associated with susceptibility to various forms of cancer. A C to T substitution at codon 187 of the gene results in almost undetectable enzyme activity in the homozygote individuals carrying the variant allele. In this study we investigated the association of the EPHX1, MPO and NQO1 gene variants with lung cancer in 126 patients and 64 healthy individuals.
Gene expression analysis was performed using the LightCycler 480 Real Time PCR system and hybridization probes. To analyze the genotypes the EPHX1, MPO and NQO1 genes were amplified by polymerase chain reaction and the presence of the gene variants was investigated by restriction fragment length polymorphism after digestion with specific restriction enzymes.
No significant differences in the distribution of the genotypes and allele frequencies were observed between the patients and the control group for the MPO gene and the two different polymorphic variants of the EPHX1 gene. The NQO1 expression levels were higher in the patients when compared to the controls but the difference was not significant. On the other hand, a significant association was observed between the CC genotype and NQO1 expression.
Citation Format: Nejat Dalay, Nur Buyru, Zubeyde Yalniz. Genetic polymorphisms in the carcinogen metabolism pathway and lung cancer risk. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A16.
Abstract A18: Pre-diagnostic serum antioxidant levels and prediction of TMPRSS2:ERG fusion status in prostate cancer
Authors: Judson Gregory , Pettersson Andreas , Meisner Allison , Mucci Lorelei 
Published: January 2014

Abstract
Background: The TMPRSS2:ERG gene fusion is a distinct molecular subtype of prostate cancer characterized by chromosomal rearrangements joining the androgen responsive TMPRSS gene with ERG, an oncogenic member of the ETS gene family. TMPRSS2:ERG is thought to be an early pathologic event occurring in 50% of prostate tumors and resulting in more than 100,000 fusion positive cancer cases each year in the US. No studies to date have examined underlying risk factors associated with development of the fusion. Oxidative stress and the production of free radicals may result in chromosomal instability and predispose to the formation of TMPRSS2:ERG positive prostate cancer. Higher levels of serum antioxidants prior to prostate cancer diagnosis may therefore be protective against later development of fusion positive cancer.
Methods: We undertook a case-control analysis nested within the prospective Physicians' Health Study and the Health Professionals Follow-up Study among men with prostate cancer (n=331) and age-matched controls (n=2139). The cohorts include pre-diagnostic bloods with antioxidant levels at baseline as well as tumor tissue to characterize TMPRSS2:ERG status among prostate cancer cases. We used multivariate logistic regression analysis to determine if plasma antioxidant levels influenced the development of the TMPRSS2:ERG fusion.
Results: Of seven antioxidants examined (alpha-tocopherol, alpha-carotene, beta-carotene, beta-cryptoxanthin, gamma-tocopherol, lutein, and lycopene), levels of beta-carotene above the lowest quartile were protective against fusion positive vs. fusion negative prostate cancer (OR 0.49, 95% CL 0.28-0.86, p = 0.01). This association was driven by a non-significantly decreased risk of fusion positive cancer vs. controls (OR 0.75, 95% CL 0.51-1.09, p = 0.13) and a significantly increased risk of fusion negative cancer vs. controls (OR 1.58, 95% CL 1.03-2.41, p = 0.03). None of the six other antioxidants were associated with fusion status, and none of the antioxidants, including beta-carotene, predicted overall prostate cancer risk.
Discussion: Previous studies examining antioxidant status and overall prostate cancer risk have been inconclusive. This is the first study to examine pre-diagnostic serum antioxidant levels in relationship to fusion status. We find that beta-carotene levels may alter prostate cancer risk based on molecular subtype.
Citation Format: Gregory Judson, Andreas Pettersson, Allison Meisner, Lorelei Mucci. Prediagnostic serum antioxidant levels and prediction of TMPRSS2:ERG fusion status in prostate cancer. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A18.
Abstract A20: Predictive value of plasma hepatocyte growth factor levels in gastric cancer risk: A Nested Case-Control Study within the Korean Multicenter Cancer Cohort
Authors: Ma Seung Hyun , Yang Jae Jeong , Kwang-Pil Ko , Shin Aesun , Shin Hai-Rim , Kang Daehee , Yoo Keun-Young , Park Sue K. 
Published: January 2014

Abstract
Background: HGF (hepatocyte growth factor) is also known as a scatter factor and is multifunctional cytokine that modulates processes such as growth, adhesion, motility, matrix degradation, invasion, and angiogenesis. We investigated whether serum HGF was a biomarker for the early detection and diagnosis of gastric cancer in a nested case-control study.
Methods: The study population was composed of 282 cases and 282 matched controls within the Korean Multicenter Cancer Cohort. Plasma HGF was measured by enzyme-linked immunosorbent assay (ELISA). Conditional logistic regression models were used to compute the odds ratio (OR) and 95% confidence intervals (CI).
Results: According to stratified analysis on age, sex, H. pylori infection, CagA and smoking, gastric cancer patients which are older, female, H. pylori positive, CagA positive and non-smokers had significantly higher serum HGF concentrations than normal controls. When conducting a logistic regression analysis of a group with the lowest concentration as a reference after dividing them into quartile according to serum HGF concentration, also, a group with the highest serum HGF concentration(≥393.7 pg/mL) showed a significantly increased risk of gastric cancer(OR=2.4 95% CI 1.4-3.9). In addition, higher serum HGF concentrations were associated with an increased risk for gastric cancer and it was statistically significant (p for trend=0.0054).
Conclusions: Our finding suggested the possibility that HGF protein can be a biomarker to predict the risk of gastric cancer.
Citation Format: Seung Hyun Ma, Jae Jeong Yang, Ko Kwang-Pil, Aesun Shin, Hai-Rim Shin, Daehee Kang, Keun-Young Yoo, Sue K. Park. Predictive value of plasma hepatocyte growth factor levels in gastric cancer risk: A nested case-control study within the Korean Multicenter Cancer Cohort. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A20.
Note: This abstract was not presented at the conference.
Abstract A25: Genetic Variants in 15q25.1 and age onset of Pancreatic Cancer
Authors: Wei Chongjuan , Huang Yu-jing , Chen Jane , Pande Mala , Amos Chris , Frazier Marsha 
Published: January 2014

Abstract
Background: Genome-wide association studies have demonstrated the association between single-nucleotide polymorphisms (SNPs) in the chromosome 15q25.1 region and an increased lung cancer risk through smoking behavior mediated by nicotine dependence susceptibility. Cigarette smoking is also a major risk factor for development of pancreatic cancer and has been reported to be associated with early onset of this disease. Therefore, we hypothesize that variation in this region may influence the age onset of the pancreatic cancer through smoking behavior.
Methods: In this preliminary study, 3 tagging SNPs in 15q25.1 region were genotyped in 427 newly-diagnosed, non-Hispanic White patients with pancreatic cancer. Two of the SNPs, rs7164594 and rs3841324, are in the CHRNA5 gene and the third SNP rs684513 is in PSMA4 gene, respectively.
Results: Our results showed that the two tagging SNPs rs7164594 and rs3841324 in CHRNA5 were not associated with age-associated risk of pancreatic cancer. However, for the tagging SNP rs684513, the variant homozygotes (CC) had a protective effect on age of onset [adjusted HR=0.69 (0.46-1.03), p=0.070], compared with the wild type and heterozygotes (GG+CG), with a 4-years difference in at age of onset [64.81 ± 2.10 vs. 60.60 ± 0.53; log-rank p= 0.042]. Further stratification analysis showed that a reduced risk associated with the variant homozygous (CC) was more pronounced in the subgroup of non-smokers and former smokers [adjusted HR=0.48 (0.26-0.91), p=0.023].
Conclusion and impact: This observation provided preliminary evidence for the association between genetic variant in the chromosomal region 15q25.1 and the age of onset of pancreatic cancer. However, a comprehensive study of all other tagging SNPs covering 15q25.1 region will be worthwhile to conduct.
Citation Format: Chongjuan Wei, Yu-jing Huang, Jane Chen, Mala Pande, Chris Amos, Marsha Frazier. Genetic variants in 15q25.1 and age onset of pancreatic cancer. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A25.
Abstract A31: Targeting Oncogenic Ras Activation for Cancer Prevention
Authors: Baoan Ji , Haojie Huang , Yan Liu , Jaroslaw Daniluk , Craig Logsdon 
Published: January 2014

Abstract
Increased Ras activity levels due to active mutations of Ras are critical for tumorigenesis. These oncogenic Ras mutations are considered to be locked in a permanent “On” state and “constitutively active”. Yet, surprisingly, expression of oncogenic Ras at physiologically levels in genetically engineered mice with “knock-in” mutant Ras has little effect on most cells. Here, we demonstrated that oncogenic K-Ras is not at all constitutively active. Rather, oncogenic K-Ras can be readily activated by upstream stimulants such as diet-induced hormones (eg. Cholecystokinin) and inflammatory stimuli (eg. PGE2 or LPS). However, unlike wild-type Ras, oncogenic K-Ras is very slow to inactivate. This effect on oncogenic K-Ras signaling kinetics leads to dramatically amplified levels of Ras activity initiated by physiologic stimuli. Sustained increase of Ras activity involves a feed-forward loop in which increased Ras activity generates more inflammatory mediators which act as Ras stimulants. High Ras activity led to acinar cell senescence and generated inflammation and fibrosis resembling the histological features of chronic inflammation with abundant precancerous lesions that spontaneously progressed to cancer only in animals expressing physiologic levels of oncogenic Ras. In summary, oncogenic Ras is not constitutively active but predisposes cells to pathological alterations dependent upon Ras activity levels. Since a large population of normal healthy humans harbors Ras mutations, in addition to targeting Ras downstream signaling pathways a reduction of factors that can activate Ras signaling may provide an important alternative cancer preventive value. These data also provide a mechanistic explanation for the link between inflammation, Ras and cancer and provide insights for cancer prevention.
Citation Format: Ji Baoan, Huang Haojie, Liu Yan, Daniluk Jaroslaw, Logsdon Craig. Targeting oncogenic Ras activation for cancer prevention. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A31.
Abstract A35: Resistant starch inhibition of azoxymethane-induced preneoplastic lesions with and without antibiotic treatment
Authors: Nelson Bridget , Ai Yongfeng , Roberts Carter , Liu Peng , Jane Jay-lin , Birt Diane 
Published: January 2014

Abstract
Colorectal cancer is one of the more prevalent cancers in Western cultures, and previous studies suggest an interaction between diet and colon carcinogenesis. Starches have been modified to be more indigestible. This allows the starch to continue through the digestive tract to the colon where it is fermented by the gut microflora to produce short chain fatty acids (SCFA). SCFA are beneficial to colon health due to their ability to regulate anti-inflammation and apoptotic pathways and inhibit colonic preneoplastic lesions such as aberrant crypt foci (ACF) and mucin depleted foci (MDF), two common lesions associated with colon cancer. By adding an antibiotic regimen, a stronger pressure will be placed on the gut microflora and this added pressure of an altered gut microflora is believed to negate the protective effects of resistant starches. Preneoplastic lesions were induced in rats with azoxymethane (AOM), a known colon cancer carcinogen, with saline used as a control. An antibiotic cocktail of vancomycin and imipenem was administered via drinking water to select groups for three days following AOM treatment. The rats were then fed experimental diets containing either control starch (CS) or high amylose-lipid complexed resistant starch (RS5) for ten weeks. Distal colon sections were collected and stained to observe ACF and MDF. There was no significant difference in ACF numbers between the CS and RS5 diet groups but there was a significant difference between the numbers of MDF observed between the two diets, with the CS rats producing more MDF than RS5 rats. A significant antibiotic effect was also observed between the two diet groups with all RS5 rats producing zero MDF and the CS treatment animals producing between 0.2-1.8 MDF. This result could indicate that RS5 does indeed retain its protective effects with an altered gut microflora. This result could also suggest that MDF may not be a suitable lesion for colon cancer studies as the highest number of MDF were observed in saline treated animals. The deliberate addition of antibiotics was a novel approach in the colon carcinogenesis-diet interaction, but the results suggest that repeated experimentation is needed to confirm the retained protective effects of resistant starch diets.
Citation Format: Bridget Nelson, Yongfeng Ai, Carter Roberts, Peng Liu, Jay-lin Jane, Diane Birt. Resistant starch inhibition of azoxymethane-induced preneoplastic lesions with and without antibiotic treatment. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A35.
Abstract A37: Beta-cryptoxanthin restores nicotine-reduced lung SIRT1 to normal levels and inhibits nicotine-promoted lung tumorigenesis and emphysema in A/J mice
Authors: Iskandar Anita , Liu Chun , Smith Donald , Hu Kang-Quan , Choi Sang-Woon , Ausman Lynne , Wang Xiang-Dong 
Published: January 2014

Abstract
Nicotine, a large constituent of cigarette smoke, is associated with an increased risk of lung cancer but the data remains inconsistent. Here, we found that nicotine treatment not only induced emphysema, but also increased both lung tumor multiplicity and volume, in 4-nitrosamino-1-(3-pyridyl)-1-butanone (NNK)-initiated lung cancer in A/J mice. This tumor-promoting effect of nicotine was accompanied with significant reductions of survival probability and lung Sirtuin 1 (SIRT1), which has been proposed as a tumor suppressor. The decreased SIRT1 was associated with increased levels of AKT phosphorylation and interleukin (il)-6 mRNA, but decreased tumor suppressor p53 and retinoic acid receptor (rar)-beta mRNA levels in the lungs. Using this mouse model, we then determine whether a xanthophyll beta-cryptoxanthin (BCX), which is associated with a reduced risk of lung cancer from a pooled analysis of seven prospective cohort studies, can inhibit the nicotine-induced emphysema and lung tumorigenesis. We found that BCX supplementation at two different doses reduced the nicotine-promoted lung tumor multiplicity and volume, as well as emphysema in mice treated with both NNK and nicotine. Moreover, BCX supplementation restored the nicotine-suppressed lung SIRT1, p53, and rar-beta to the levels of the control group, increased the survival probability, and decreased the lung il-6 mRNA and AKT phosphorylation levels. The present study indicates that the SIRT1 is a potential target for the action of BCX against emphysema and lung cancer. In addition, our study established a relevant animal lung cancer model for studying tumor growth within emphysemateous microenvironments.
Citation Format: Anita Iskandar, Chun Liu, Donald Smith, Kang-Quan Hu, Sang-Woon Choi, Lynne Ausman, Xiang-Dong Wang. Beta-cryptoxanthin restores nicotine-reduced lung SIRT1 to normal levels and inhibits nicotine-promoted lung tumorigenesis and emphysema in A/J mice. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A37.
Abstract A39: Dietary supplementation with curcumin enhances metastatic growth of Lewis lung carcinoma in mice
Authors: Yan Lin 
Published: January 2014

Abstract
The present study investigated the effects of dietary supplementation with curcumin (the principal curcuminoid of the popular Indian spice turmeric) on spontaneous metastasis of Lewis lung carcinoma (LLC) in female C57/BL6 mice. Mice were fed the AIN93G control diet or that diet supplemented with 2% or 4% curcumin for 5 weeks at which time they were injected subcutaneously with 2.5 x 105 viable LLC cells. The subcutaneous primary tumor was surgically removed when it reached approximately 8 mm in diameter, and the experiment was terminated 10 days after the surgery. There was no difference in pulmonary metastatic yield among the groups. Curcumin supplementation at either dietary level did not significantly affect tumor growth. However, the combine data from both curcumin groups showed that curcumin treatment increased tumor cross-sectional area by 46% (p &lt; 0.05) and tumor volume by 70% (p &lt; 0.05) compared with the controls. Curcumin supplementation increased plasma concentrations of the angiogenic factors fibroblast growth factor-basic (p &lt; 0.05) and vascular endothelial growth factor (p &lt; 0.05), as well as the inflammatory cytokines interleukin-1β (p &lt; 0.05) and monocyte chemotactic protein-1 (p &lt; 0.05) compared with the controls. These results demonstrate that curcumin does not prevent metastasis, and indicate that it can enhance metastatic growth of LLC in mice, perhaps through up-regulation of angiogenesis and inflammation.
Citation Format: Lin Yan. Dietary supplementation with curcumin enhances metastatic growth of Lewis lung carcinoma in mice. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A39.