bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1822: Age-period-cohort (APC) analysis of primary bone cancer incidence rates in the United States (1976 – 2005)
Authors: Anfinsen Kristin P. , Bray Freddie I. , Troisi Rebecca , Jonasdottir Thora J. , Bruland Oyvind S. , Devesa Susan S. , Grotmol Tom 
Published: February 2011

Abstract
BACKGROUND: Primary bone cancer comprises three major histological subtypes: osteosarcoma (OS), Ewing sarcoma (ES) and chondrosarcoma (CS). The most frequent subtype, OS, primarily occurs in adolescence, but has a second peak at the oldest ages, usually attributed to late effects of radiotherapy and chemotherapy, and Paget's disease. The adolescent age distribution of ES resembles that of OS, suggesting a link between the onset of puberty and these subtypes of bone cancer. CS is rare in childhood, and incidence rates, unlike those of OS and ES, increase fairly uniformly with age. Given the limited knowledge about the etiology of primary bone cancer, and the unusual age-incidence distribution for OS and ES, we undertook an APC analysis to determine whether incidence varied by birth cohort or calendar period. For other cancers, such as testis and breast, the identification of cohort patterns has generated new hypotheses regarding environmental risk factors. METHODS: We fit an APC model to incidence data among U.S. whites for OS, ES and CS obtained from nine registries of the Surveillance, Epidemiology, and End Results (SEER) program, which covers about 10% of the U.S. population, 1976-2005. The purpose was to examine the temporal development of each bone cancer subtype, with an aim to providing etiologic clues as to the role of birth cohort-related changes. RESULTS: Incidence of OS decreased between 1976 and 2005 among those 60 years and older, and rates declined among cohorts born 1905-34. The risk of CS doubled among females 20-69 years, with rates increasing among consecutive birth cohorts born 1925-54, whereas those of males were unaltered. For both sexes, ES incidence rates tended to be stable. CONCLUSIONS: The risk reduction in OS at older ages was most likely due to improved radiotherapy and more effective chemotherapy. The CS risk increase in females corresponds to birth cohorts who were increasingly exposed to estrogens, both in terms of contraceptives (from 1960 onwards), and hormone replacement therapy (from 1950 onwards). In support of our hypothesis that estrogens are involved in the increase in CS among women over time, in vitro studies show that the estrogen signaling pathway stimulates proliferation of both normal and malignant chondrocytes. Further studies are warranted to pursue the possible etiological significance of estrogen exposure in CS risk.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1822.
Abstract 1825: Maternal alcohol consumption and childhood acute myeloid leukemia risk
Authors: Song Minkyo , Lee Kyoung-Mu , Han Sohee , Park Sue K. , Ahn Hyo Seop , Shin Hee Young , Kang Hyoung Jin , Koo Hong Hoe , Seo Jong Jin , Choi Ji Eun , Ahn Yoon-Ok , Kang Daehee 
Published: February 2011

Abstract
Background: Leukemia is the most common malignancy in children. The etiology of childhood leukemia is mostly unknown, although some environmental factors such as ionizing radiation and parental alcohol and tobacco use may play a causative role in leukemia.
Methods: To investigate the association between parental alcohol consumption and childhood leukemia in a hospital-based case-control study in Korea, histologically-confirmed incident childhood leukemia cases (n=365) aged 0-18 years old were recruited from three teaching hospitals located in Seoul, Korea, between May 2003 and August 2008. Non-cancer controls (n=558) aged 0-18 years old without medical history of childhood cancer were recruited from the Department of Pediatrics of the same hospitals. Controls were frequency-matched to cases by 5-year age intervals and sex (cases: controls=1:1). Leukemia risks were estimated as odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression analysis adjusted for age, sex, parent's education, and birth weight (&lt;3.25, 3.25-3.70, ≥3.70 kg). In addition to conducting analyses of all childhood leukemia, we calculated histologic subtype-specific ORs for acute lymphoblastic leukemia (ALL; n=200) and acute myeloid leukemia (AML; n=88).
Results: Among general characteristics, higher birth weight and parental education were associated with childhood leukemia risk (P&lt;0.05). The proportion of drinking mothers was significantly higher among all leukemia cases than controls (58% vs. 49%: OR=1.4, 95% CI=1.00-1.83), whereas no association was observed for paternal alcohol consumption (87% vs. 83%). When the analysis was restricted to AML cases, the association between maternal drinking and cancer risk became stronger (OR=1.8, 95% CI=1.06-2.90). Drinking frequency of the mothers was also associated with the increased risk. (≥1/month vs. &lt;1/month; OR=1.7, 95% CI=1.10-2.28). Also, drinking duration of more than one year before pregnancy increased the risk of AML (OR=1.7, 95% CI= 1.00-2.85). No association was found between parental alcohol consumption and ALL risk.
Conclusion: Our results suggest that maternal alcohol consumption is associated with AML among Korean children. However, larger studies need to be conducted to replicate our findings.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1825.
Abstract 1837: Exposure to Aristolochic Acid is associated with endemic (Balkan) nephropathy
Authors: Edwards Karen L. , Wang Jia Yin , Snappin Katherine , Sonicki Zdenko , Miletic-Medved Marcia , Grollman Arthur P. , Jelakovic Bojan 
Published: February 2011

Abstract
Endemic (Balkan) Nephropathy (EN) is a rare, chronic tubulointerstitial nephritis that gradually progresses to end state renal disease. EN is also associated with development of urothelial cancer. EN has been the subject of many epidemiologic investigations during the past 50 years and is now thought to occur more broadly than just the endemic Balkan regions. Numerous hypotheses have been investigated but no causal factor has been identified. Exposure to Aristolochic Acid (AA) was proposed 30 years ago as a potential cause of EN, but was dismissed. The most likely route of human exposure to AA is via ingestion of home-baked bread prepared from flour contaminated by seeds of Aristolochia clematitis.
Methods: Studies are underway in Croatia in collaboration with US investigators to evaluate this hypothesis. Data for this study comes from a population-based survey conducted in 2005 that includes 1081 subjects from 3 endemic and 1 nonendemic village. Logistic regression was used to evaluate the association between exposure to AA and EN.
Results: Exposure to Aristolochic Acid (AA) from bread consumption is associated with a nearly 2 fold increase in risk of EN (OR=1.7; 95%CI: 1.07,2.98), growing wheat for flour is associated with a 3 fold increase risk (OR=3.5; 1.27, 10.1)), and recalling the AA containing weed in the wheat field was also significant (OR=2.4; 1.32, 4.62). Adjustment for covariates reduced the significance, but the elevated risk was still observed. A larger population-based assessment of several new villages in Croatia was recently completed.
Conclusion: Understanding the etiology of this debilitating disease is the first step in developing an effective prevention strategy. Next steps will include evaluating specific genetic components and their interactions with exposure to AA.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1837.
Abstract 1845: Genetic analyses of MGMT in familial gliomas and colorectal cancer
Authors: Moutinho Cátia , Blanco Ignacio , Martinez Ramon , Esteller Manel 
Published: February 2011

Abstract
DNA repair is an important area of research in cancer biology. The O6-methylguanine DNA methyltransferase (MGMT) enzyme is one of the key players in this area. When deregulated affects DNA repair capacity and it is involved in cancer formation. In eukaryotes the MGMT enzyme is the first line of defense against the adverse effects of DNA alkyl-lesions that are potent mutagenic and cytotoxic lesions. Evidence for MGMT suppressing cancer susceptibility in humans include the loss of expression by epigenetic silencing in a variety of human cancers, including &gt; 30% of colorectal, brain, lung, lymphoma, head and neck cancers. Moreover, these cancers frequently show higher incidence of G to A transitions mutations in oncogene v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) and in the tumour suppressor gene tumour protein p53 (TP53) compared to tumours with normal MGMT expression. A single report has described somatic mutations in MGMT gene. However, there are several reports of individual differences in MGMT activity. A few germline variants affecting this gene have been described, but the functional relevance of these nucleotides changes is unclear. There are many familial colorectal cancers (CCR) and familial gliomas for which it has not been described an associated germline mutation. In order to see if MGMT tumour suppressor gene could be genetically involved on that, we did a germline screening of 78 CCR probands and 8 gliomas probands from familial cases. As control we also did the screening of 80 normal DNAs lymphocytes from healthy volunteers. For that we performed direct sequencing of all MGMT exons. We found polymorphisms (SNPs) already described, where are included the three common non-synonymous SNPs Leu84Phe, Ile143Val and Lys178Arg. The frequency of SNPs in probands lymphocytes was the same as in normal DNA lymphocytes. The study is ongoing and further extensive research is warranted.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1845.
Abstract 1848: Folliculin (FLCN) sequence variants involved in Birt-Hogg-Dube syndrome
Authors: Lim Derek HK , Rehal Pauline K. , Nahorski Michael S. , Macdonald Fiona , Claessens Tijs , Geel Michel Van , Gijezen Lieke , Gille Johan JP , Giraud Sophie , Richard Stephane , Steensel Maurice Van , Menko Fred , Maher Eamonn 
Published: February 2011

Abstract
Background:
Birt-Hogg-Dubé (BHD) syndrome is an autosomal dominantly inherited familial cancer syndrome characterized most commonly by the development of facial fibrofolliculomas, pulmonary cysts (predisposing to spontaneous pneumothorax) and renal cancer. Germline mutations in FLCN on 17p11.2 have been reported in patients with BHD and also in patients with isolated familial primary spontaneous pneumothorax and familial clear cell renal cell carcinoma without other features of BHD. The function of the FLCN gene product, folliculin, is not well characterized but recent studies have suggested that it may be implicated in the regulation of several key signalling pathways including the AMPK-mTOR route.
Methods:
We previously established an online locus-specific database (LSDB) for FLCN sequence variants at www.lovd.nl/flcn. Variants in the database have been curated from the published literature and novel unpublished sequence variants submitted to the database from diagnostic and research laboratories working on BHD syndrome. The entries in the database were analyzed looking at the variant type and distribution and associated phenotype.
Results:
The database currently contains a total of 115 unique sequence variants (including 70 pathogenic, 7 probably pathogenic, 1 variant of unknown significance and 37 single nucleotide polymorphisms) in FLCN. The majority of pathogenic mutations results in protein truncation whilst a minority are splice-site alterations. An up to date summary of the variants and their associated phenotype will be presented.
Conclusion:
Pathogenic mutations are found throughout the coding regions (exons 4-14) and there are no apparent genotype-phenotype correlations. The FLCN mutation database available at www.lovd.nl/flcn offers a valuable resource and tool for clinicians involved in the management of BHD patients, clinical geneticists and researchers. Researchers can directly submit new sequence variants online to the database or by e-mailing the author.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1848.
Abstract 1857: 3p12.3 and 7q36.3 harbor genes associated with hereditary breast and colorectal carcinomas
Authors: Abreu Francine B. , Santos Erika M.M. , Rossi Benedito M. , Kowalski Luiz P. , Brentani Ricardo R. , Rogatto Silvia R. 
Published: February 2011

Abstract
Lynch syndrome (LS) is the most common hereditary syndrome that predisposes to colorectal cancer (CRC). LS is associated with susceptibility to proximal colon cancer, multiple primary (CRC) and extra-colonic tumors. According to Registration of Hereditary Colorectal Cancer (RHCC) of AC Camargo Hospital of Brazil, breast cancer is the most frequent extra-colonic tumor among women with suspicion of hereditary CRC, suggesting the possibility of a new syndrome known as Hereditary Breast and Colorectal Cancer (HBCC). Array comparative genomic hybridization (array CGH) is the high-resolution laboratory technique of choice for the detection of chromosomal DNA copy number alterations on a genome-wide scale. The aim of the present study was to identify copy number alterations in genes related to predisposition in HBCC syndrome. Array comparative genomic hybridization was performed using Human 4 × 180K Oligoarrays (G4449A, Agilent) in 47 individuals from families showing HBCC phenotype. For each sample, 800 ng of DNA were fragmented by a double enzymatic digestion (AluI + RsaI). DNA from peripheral blood leukocytes and control DNA from Promega (Human Genomic DNA Female G1521) were labeled with CY3-dCTP and CY5-dCTPs, respectively, and hybridized at 65°C for 17 h. The chips were scanned on an Agilent DNA Microarray Scanner and image analysis was done using the Feature-Extraction version 10.1.1.1 software (Agilent Technologies). Raw copy number ratio data were transferred to the Agilent Genomic Workbench Software (version 5.0.14) for further analysis. It was detected copy number variations involving 36 regions previously described in genome databases. Furthermore, it was observed loss at 3p12.3 in two individuals. One patient presented breast cancer and CCR while the other one had breast carcinoma. Both of them had breast cancer around the 50 years. In both families, their relatives had CCR, breast cancer and endometrial cancer, which is another extra-colonic tumor found among patients with LS. In a third women with breast and colorectal carcinomas was detected deletion at 7q36.3. Germline copy number alterations may indicate new genes associated with cancer predisposition. Our results suggest that 3p12.3 and 7q36.3 harbor genes associated with hereditary breast and colorectal carcinomas. Additional members of these families are being evaluated to confirm the involvement of these regions as candidate genes. Financial Support: FAPESP (2008/57887-9) and CNPq (57589/2008-9).
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1857.
Abstract 1859: Breast cancer risk:tp53 genotyping in a Nigerian population
Authors: Kasvosve Nancy N. , Fackenthal Jim , Zhang Jing , Olopade Olufunmilayo 
Published: February 2011

Abstract
Background: Women of African descent have a lower incidence of breast cancer than other ethnicities but higher mortality rates. Their tumors are characterized by an earlier age of onset, aggressive behavior, poor prognosis, and molecular characteristics of “triple negative” status (i.e. lacking detectable ER, PR, and HER2/neu expression). These characteristics are also typical of tumors carrying somatic TP53 mutations. Experimental evidence has shown that somatic inactivation of the TP53 pathway is necessary for tumor development. Null or strongly hypomorphic TP53 mutations inherited through the germline are associated with a high likelihood of tumorigenesis. Studies on different ethnic populations show inheritance of TP53 variants, especially the R72P polymorphism, to be associated with risk of tumor formation in breast and other tissues. These observations suggest that TP53 gene activity plays a significant role in promoting tumor development in tissues.
Hypothesis: As the TP53 R72P polymorphism has been associated with cancer risk in non-African populations, and patients of African ancestry frequently have tumors with TP53 mutation-like characteristics, we hypothesize the R72P variant may be associated with low-penetrance breast cancer risk in a Nigerian/Yoruba population. In addition, this variant may be associated with the triple negative tumor subtype.
Methods: The study is a case-control analysis using 213 breast cancer patients and 213 unaffected controls from the University Hospital in Ibadan, Nigeria. The TP53 R72P genotype was determined by direct sequencing of TP53 exon 4, amplified by PCR from peripheral genomic DNA. Chi-square statistical analysis was used to compare frequencies of individual alleles and genotypes in between cases and controls.
Results and Conclusions: 130 cases and 207 controls have been genotyped so far. Genotype frequencies for G/G, G/C, and C/C were 21%, 38%, and 41% in cases and 12%, 46% and 42% in the controls, respectively with a p value of 0.11 and an odds ratio of 1.24 at 95% CL. Preliminary results indicate a trend toward risk associated with the G/G genotype, though these results do not yet reach statistical significance. This analysis may provide important clues to the genetic basis of cancer risk and tumor etiology in patients of African ancestry.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1859.
Abstract 1865: ERCC2 polymorphisms, smoking, and risk of breast cancer
Authors: Conlon Michael S. , Bewick Mary A. 
Published: February 2011

Abstract
The nucleotide excision repair (NER) pathway is important in the repair of bulky DNA lesions, including those that may be induced by cigarette smoking. Excision Repair Cross-Complementing Rodent Repair Deficiency, Complementation Group 2 (ERCC2) is an important gene in the NER pathway. Previous research suggests that polymorphisms in this gene may be associated with altered DNA repair capacity, cancer risk and treatment outcome. This study investigated whether two common single nucleotide polymorphisms (SNPs) in ERCC2 (ERCC2 Asp312Gln and ERCC2 Lys751Gln) were associated with risk of breast cancer, or modified a breast cancer risk associated with smoking. We used data previously collected from a primarily Caucasian population in northeastern Ontario Canada of 347 women diagnosed (2002-2004) with breast cancer and 775 population-based controls. The mailed study package contained a questionnaire that provided information on known breast cancer risk factors and lifetime residential and occupational history of exposure to passive and active smoking, and a buccal swab for genetic analyses. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using unconditional logistic regression, and used a refined referent group that excluded women with substantial exposure to passive smoke and who were never active smokers. Both SNPs were in Hardy-Weinburg Equilibrium (HWE) in controls. Overall, there was no significant association with either SNP and risk of breast cancer. Women who were active smokers of long duration (&gt; 29 years), or high (&gt;20) pack-years, were at significantly increased risk of breast cancer if they carried the G allele of ERCC2Asp312Gln, with ORs of 1.72 (95% CI 1.10-2.68) and 1.68 (95% CI 1.09-2.61) and p=0.03 and 0.007 for trend, respectively. Similar significantly increased risks were observed in women who carried the A allele of ERCC2 Lys751Gln, with ORs of 1.77 (95% CI 1.14-2.76) and 1.67 (95% CI 1.08-2.58) and p=0.02 and 0.01 for trend, respectively. In conclusion, our data suggest that polymorphisms in the NER pathway may modify a smoking-breast cancer relationship.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1865.
Abstract 1887: Distinct molecular targets of blueberry and black raspberry in breast cancer prevention
Authors: Ravoori Srivani , Kausar Hina , Aqil Farrukh , Gupta Ramesh C. 
Published: February 2011

Abstract
We previously demonstrated protection with berries in diet, against estrogen-induced ACI rat mammary tumorigenesis, by inhibition of proliferation as early as 3 weeks of estrogen administration. In this study, blueberry (BB) and black raspberry (BRB) were administered in diet at 5% 2 weeks prior to implantation with 1.2 cm silastic implants containing 9 mg 17β-estradiol. Rats were killed at 3 weeks, 3 months and ∼7 months, when the tumor incidence in control group reached 80%. Analysis revealed significant reduction (p&lt;0.05) in tumor volume (Control: 801.2±105.3 mm3; BB: 395±97.9 mm3; BRB: 461±109.8 mm3) and tumor multiplicity (Control: 6.9±0.9; BB: 4.4±0.6; BRB: 4.3±0.6) by the berry diets. Most important finding is that while BB was more effective in reducing the tumor volume, BRB was more efficient in delaying the first tumor incidence, by 5 weeks (p&lt;0.05). We also investigated the key molecules of cell-cycle regulation, cell proliferation and transcription. The cell-cycle regulatory molecule cyclin D1 which was up-regulated by 3-4-fold in mammary tissues with estrogen treatment, was significantly down-regulated by BB diet as early as 3 weeks and remained down-regulated during the entire tumorigenesis period (p&lt;0.05), as detected by western blot. BRB diet did not show any significant down-regulation of cyclin D1. Estrogen receptor α, on the other hand, which was significantly overexpressed with estrogen treatment at all the three time points, was significantly offset by BRB diet, but it was not well pronounced with BB diet. Molecules downstream of these effector proteins are currently being explored. While BB contains five distinct anthocyanidins (delphinidin, cyanidin, malvidin, peonidin, and petunidin) and insignificant levels of ellagic acid, BRB contains chiefly cyanidin and high levels of ellagic acid. Thus, the distinct and specific molecular targets and pathways involved in the protective actions of the two berries corroborate their distinct phytochemical signatures. (Supported by CA-118114 and Agnes Brown Duggan Endowment).
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1887.