bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from Folate Pathway Gene Polymorphisms and Risk of Childhood Brain Tumors: Results from an Australian Case–Control Study
Authors: Greenop Kathryn R. , Scott Rodney J. , Attia John , Bower Carol , de Klerk Nicholas H. , Norris Murray D. , Haber Michelle , Jamieson Sarra E. , van Bockxmeer Frank M. , Gottardo Nicholas G. , Ashton Lesley J. , Armstrong Bruce K. , Milne Elizabeth
Published: April 2023

Abstract
Background: Recent research suggests that maternal folic acid supplementation is associated with a reduced risk of childhood brain tumors (CBT); polymorphisms in folate pathway genes could modify this association or directly influence CBT risk.

Methods: Associations between risk of CBT and folate pathway polymorphisms were investigated in a population-based case–control study in Australia (2005–2010). Cases were recruited through all Australian pediatric oncology centers and controls by national random digit dialing. Data were available from 321 cases and 552 controls. Six polymorphisms were genotyped in children and parents (MTHFR 677C>T, MTHFR 1298A>C, MTRR 66A>G, MTR 2756A>G, MTR 5049C>A, and CBS 2199 T>C). Maternal folic acid use was ascertained via questionnaire. ORs were estimated using unconditional logistic regression. Case–parent trio analyses were also undertaken.

Results: There was weak evidence of a reduced risk of CBT for the MTRR 66GG genotype in the child or father: ORs 0.71 [95% confidence interval (CI), 0.48–1.07]; 0.54 (95% CI, 0.34–0.87), respectively. Maternal prepregnancy folic acid supplementation showed a stronger negative association with CBT risk where the child, mother, or father had the MTRR 66GG genotype (Pinteraction = 0.07, 0.10, and 0.18, respectively).

Conclusions: Evidence for an association between folate pathway genotypes and CBT is limited in this study. There was possible protection by the MTRR 66GG genotype, particularly when combined with maternal prepregnancy folic acid supplementation; these results are novel and require replication.

Impact: The possible interaction between folic acid supplementation and MTRR 66A>G, if confirmed, would strengthen evidence for prepregnancy folate protection against CBT. Cancer Epidemiol Biomarkers Prev; 24(6); 931–7. ©2015 AACR.
Data from Tobacco Use and Cancer Risk in the Agricultural Health Study
Authors: Andreotti Gabriella , Freedman Neal D. , Silverman Debra T. , Lerro Catherine C. , Koutros Stella , Hartge Patricia , Alavanja Michael C. , Sandler Dale P. , Freeman Laura Beane
Published: April 2023

Abstract
Background: Cigarettes are well known to cause cancer, but less is known about the risks of other tobacco products and use of more than one product.

Methods: We examined cancer incidence in relation to exclusive use of six tobacco products [cigarettes, other combustibles (pipe, cigar, cigarillo), and smokeless tobacco (chewing tobacco, snuff)] in the Agricultural Health Study. We also examined the added cancer risks associated with use of cigarettes and other tobacco products.

Results: In our study population of 84,015, ever use of smokeless tobacco was higher than the general United States population, whereas cigarette use was lower and other combustible product use was about the same. The strongest associations for exclusive ever use were for lung cancer [cigarettes HR = 15.48; 95% confidence interval (CI), 11.95–20.06; other combustible tobacco HR = 3.44; 95% CI, 1.53–7.71; smokeless tobacco HR = 2.21; 95% CI, 1.11–4.42]. Compared with exclusive cigarette smokers, cigarette smokers who additionally ever-used another combustible product had higher risks of smoking-related cancers (HR = 1.16; 95% CI, 1.04–1.30), especially among those who smoked cigarettes for more than 15 years.

Conclusions and Impact: Cigarette smokers who additionally ever used smokeless tobacco had cancer risks similar to exclusive cigarette smokers. Users of cigarettes and other combustible tobacco may have higher risks of certain cancers than exclusive cigarette users. Cancer Epidemiol Biomarkers Prev; 26(5); 769–78. ©2016 AACR.
Data from Gene Expression Profiling in True Interval Breast Cancer Reveals Overactivation of the mTOR Signaling Pathway
Authors: Rojo Federico , Domingo Laia , Sala Maria , Zazo Sandra , Chamizo Cristina , Menendez Silvia , Arpi Oriol , Corominas Josep Maria , Bragado Rafael , Servitja Sonia , Tusquets Ignasi , Nonell Lara , Macià Francesc , Martínez Juan , Rovira Ana , Albanell Joan , Castells Xavier
Published: April 2023

Abstract
Background: The development and progression of true interval breast cancers (tumors that truly appear after a negative screening mammogram) is known to be different from screen-detected cancers. However, the worse clinical behavior of true interval cancers is not fully understood from a biologic basis. We described the differential patterns of gene expression through microarray analysis in true interval and screen-detected cancers.

Methods: An unsupervised exploratory gene expression profile analysis was performed on 10 samples (true interval cancers = 5; screen-detected cancers = 5) using Affymetrix Human Gene 1.0ST arrays and interpreted by Ingenuity Pathway Analysis. Differential expression of selected genes was confirmed in a validation series of 91 tumors (n = 12; n = 79) by immunohistochemistry and in 24 tumors (n = 8; n = 16) by reverse transcription quantitative PCR (RT-qPCR), in true interval and screen-detected cancers, respectively.

Results: Exploratory gene expression analysis identified 1,060 differentially expressed genes (unadjusted P < 0.05) between study groups. On the basis of biologic implications, four genes were further validated: ceruloplasmin (CP) and ribosomal protein S6 kinase, 70 kDa, polypeptide 2 (RPS6KB2), both upregulated in true interval cancers; and phosphatase and tensin homolog (PTEN) and transforming growth factor beta receptor III (TGFBR3), downregulated in true interval cancers. Their differential expression was confirmed by RT-qPCR and immunohistochemistry, consistent with mTOR pathway overexpression in true interval cancers.

Conclusions: True interval and screen-detected cancers show differential expression profile both at gene and protein levels. The mTOR signaling is significantly upregulated in true interval cancers, suggesting this pathway may mediate their aggressiveness.

Impact: Linking epidemiologic factors and mTOR activation may be the basis for future personalized screening strategies in women at risk of true interval cancers. Cancer Epidemiol Biomarkers Prev; 23(2); 288–99. ©2013 AACR.
Data from Evaluation of Buccal Cell Samples for Studies of Oral Microbiota
Authors: Yu Guoqin , Phillips Steve , Gail Mitchell H. , Goedert James J. , Humphrys Michael , Ravel Jacques , Ren Yanfang , Caporaso Neil E.
Published: April 2023

Abstract
Background: The human microbiota is postulated to affect cancer risk, but collecting microbiota specimens with prospective follow-up for diseases will take time. Buccal cell samples have been obtained from mouthwash for the study of human genomic DNA in many cohort studies. Here, we evaluate the feasibility of using buccal cell samples to examine associations of human microbiota and disease risk.

Methods: We obtained buccal cells from mouthwash in 41 healthy participants using a protocol that is widely employed to obtain buccal cells for the study of human DNA. We compared oral microbiota from buccal cells with that from eight other oral sample types collected by following the protocols of the Human Microbiome Project. Microbiota profiles were determined by sequencing 16S rRNA gene V3–V4 region.

Results: Compared with each of the eight other oral samples, the buccal cell samples had significantly more observed species (P < 0.002) and higher alpha diversity (Shannon index, P < 0.02). The microbial communities were more similar (smaller beta diversity) among buccal cells samples than in the other samples (P < 0.001 for 12 of 16 weighted and unweighted UniFrac distance comparisons). Buccal cell microbial profiles closely resembled saliva but were distinct from dental plaque and tongue dorsum.

Conclusions: Stored buccal cell samples in prospective cohort studies are a promising resource to study associations of oral microbiota with disease.

Impact: The feasibility of using existing buccal cell collections in large prospective cohorts allows investigations of the role of oral microbiota in chronic disease etiology in large population studies possible today. Cancer Epidemiol Biomarkers Prev; 26(2); 249–53. ©2016 AACR.
Data from Alcohol Drinking Mediates the Association between Polymorphisms of ADH1B and ALDH2 and Hepatitis B–Related Hepatocellular Carcinoma
Authors: Liu Jessica , Yang Hwai-I , Lee Mei-Hsuan , Jen Chin-Lan , Hu Hui-Han , Lu Sheng-Nan , Wang Li-Yu , You San-Lin , Huang Yen-Tsung , Chen Chien-Jen
Published: April 2023

Abstract
Background: The role of polymorphisms on ADH1B and ALDH2 in patients with chronic hepatitis B is unclear. This study aims to examine whether alcohol drinking mediates the association between two ADH1B and ALDH2 polymorphisms and the risk of hepatocellular carcinoma among chronic hepatitis B patients.

Methods: A total of 3,824 individuals were enrolled in this study. Two SNPs, rs1229984 (ADH1B) and rs671 (ALDH2), were genotyped using the Affymetrix Axiom Genome-Wide CHB1 Array (Affymetrix, Inc). Multivariate unconditional logistic regression and mediation analyses were used, comparing CT or TT with CC for rs1229984 and GA and AA with GG for rs671.

Results: There were 602 cases of hepatocellular carcinoma and 3,222 controls. Frequencies of the rs1229984 (ADH1B) T allele and rs671 (ALDH2) A allele were 72.9% and 28.8%, respectively. Individuals who carried at least one deficient allele for both SNPs were significantly less likely to become habitual alcohol drinkers, with an OR and 95% confidence interval (CI) of 0.24 (0.15–0.40). Alleles for rs1229984 (ADH1B) and rs671 (ALDH2) were not associated with hepatocellular carcinoma in multivariate analyses. However, mediation analyses showed that the rs1229984 T allele, rs671 A allele, and two SNPs combined were significantly associated with decreased hepatocellular carcinoma risk, mediated through alcohol drinking, with an OR (95% CI) of 0.87 (0.79–0.96), 0.70 (0.61–0.82), and 0.73 (0.58–0.88), respectively.

Conclusions: Polymorphisms on ADH1B and ALDH2 had significant indirect effects on hepatocellular carcinoma risk, mediated through alcohol drinking.

Impact: Future genetic studies of chronic hepatitis B and hepatocellular carcinoma must take mediation effects into consideration. Cancer Epidemiol Biomarkers Prev; 25(4); 693–9. ©2016 AACR.
Data from Genetic Variation in Prostate-Specific Antigen–Detected Prostate Cancer and the Effect of Control Selection on Genetic Association Studies
Authors: Knipe Duleeka W. , Evans David M. , Kemp John P. , Eeles Rosalind , Easton Douglas F. , Kote-Jarai Zsofia , Al Olama Ali Amin , Benlloch Sara , Donovan Jenny L. , Hamdy Freddie C. , Neal David E. , Davey Smith George , Lathrop Mark , Martin Richard M.
Published: April 2023

Abstract
Background: Only a minority of the genetic components of prostate cancer risk have been explained. Some observed associations of SNPs with prostate cancer might arise from associations of these SNPs with circulating prostate-specific antigen (PSA) because PSA values are used to select controls.

Methods: We undertook a genome-wide association study (GWAS) of screen-detected prostate cancer (ProtecT: 1,146 cases and 1,804 controls); meta-analyzed the results with those from the previously published UK Genetic Prostate Cancer Study (1,854 cases and 1,437 controls); investigated associations of SNPs with prostate cancer using either “low” (PSA < 0.5 ng/mL) or “high” (PSA ≥ 3 ng/mL, biopsy negative) PSA controls; and investigated associations of SNPs with PSA.

Results: The ProtecT GWAS confirmed previously reported associations of prostate cancer at three loci: 10q11.23, 17q24.3, and 19q13.33. The meta-analysis confirmed associations of prostate cancer with SNPs near four previously identified loci (8q24.21,10q11.23, 17q24.3, and 19q13.33). When comparing prostate cancer cases with low PSA controls, alleles at genetic markers rs1512268, rs445114, rs10788160, rs11199874, rs17632542, rs266849, and rs2735839 were associated with an increased risk of prostate cancer, but the effect-estimates were attenuated to the null when using high PSA controls (Pheterogeneity in effect-estimates < 0.04). We found a novel inverse association of rs9311171-T with circulating PSA.

Conclusions: Differences in effect-estimates for prostate cancer observed when comparing low versus high PSA controls may be explained by associations of these SNPs with PSA.

Impact: These findings highlight the need for inferences from genetic studies of prostate cancer risk to carefully consider the influence of control selection criteria. Cancer Epidemiol Biomarkers Prev; 23(7); 1356–65. ©2014 AACR.
Data from Smoking, Lower Gastrointestinal Endoscopy, and Risk for Colorectal Cancer
Authors: Hoffmeister Michael , Jansen Lina , Stock Christian , Chang-Claude Jenny , Brenner Hermann
Published: April 2023

Abstract
Background: Lower gastrointestinal endoscopy can decrease colorectal cancer risk strongly through detection and removal of adenomas. Thus, we aimed to investigate whether utilization of lower gastrointestinal endoscopy modifies the effect of lifetime smoking exposure on colorectal cancer risk in a population-based case–control study.

Methods: In this study from Southern Germany including 2,916 patients with colorectal cancer and 3,044 controls, information about lifetime smoking and other risk factors was obtained from standardized interviews. Self-reported endoscopies were validated by medical records. Multivariate logistic regression was performed to investigate associations of smoking with colorectal cancer risk after stratification by utilization of lower gastrointestinal endoscopy in the preceding 10 years.

Results: Median age of patients and controls was 69 and 70 years, respectively. Former regular smoking was associated with increased colorectal cancer risk in the group with no previous endoscopy [adjusted OR, 1.50; 95% confidence interval (CI), 1.28–1.75], whereas no association was found in the group with preceding endoscopy (OR, 1.05; CI, 0.83–1.33; P for interaction <0.01). Lower gastrointestinal endoscopy did not modify the association of smoking and colorectal cancer risk among current smokers and among the more recent quitters.

Conclusions: Our results suggest that the increased risk of colorectal cancer among former regular smokers is essentially overcome by detection and removal of adenomas at lower gastrointestinal endoscopy. However, risk of colorectal cancer was increased if smoking was continued into higher adult age.

Impact: The strong protective effect of lower gastrointestinal endoscopy may be compromised by continued smoking. Smoking cessation may increase the efficacy of lower gastrointestinal endoscopy. Cancer Epidemiol Biomarkers Prev; 23(3); 525–33. ©2014 AACR.
Data from International Variation in Lung Cancer Mortality Rates and Trends among Women
Authors: Torre Lindsey A. , Siegel Rebecca L. , Ward Elizabeth M. , Jemal Ahmedin
Published: April 2023

Abstract
Background: There is no recent comprehensive global analysis of lung cancer mortality in women. We describe contemporary mortality rates and trends among women globally.

Methods: We used the World Health Organization's Cancer Mortality Database covering 65 populations on six continents to calculate age-standardized (1960 Segi world standard) lung cancer death rates during 2006 to 2010 and annual percent change in rates for available years from 1985 to 2011 and for the most recent five data years by population and age group (30–49 and 50–74 years).

Results: Lung cancer mortality rates (per 100,000) among young women (30–49 years) during 2006 to 2010 ranged from 0.7 in Costa Rica to 14.8 in Hungary. Rates among young women were stable or declining in 47 of 52 populations examined. Rates among women 50 to 74 years ranged from 8.8 in Georgia and Egypt to 120.0 in Scotland. In both age groups, rates were highest in parts of Europe (Scotland, Hungary, Denmark) and North America and lowest in Africa, Asia, and Latin America. Rates in older women were increasing for more than half (36/64) of populations examined, including most countries in Southern, Eastern, and Western Europe and South America.

Conclusions: Although widespread reductions in lung cancer in young women provide evidence of tobacco control success, rates continue to increase among older women in many countries.

Impact: More concentrated efforts to initiate or expand tobacco control programs in these countries globally will be required to attenuate the future lung cancer burden. Cancer Epidemiol Biomarkers Prev; 23(6); 1025–36. ©2014 AACR.
Data from Serum Vascular Adhesion Protein-1 Level Predicts Risk of Incident Cancers in Subjects with Type II Diabetes
Authors: Yu Tse-Ya , Li Hung-Yuan , Jiang Yi-Der , Chang Tien-Jyun , Wei Jung-Nan , Lin Chi-Ming , Chu Ching-Chi , Chuang Lee-Ming
Published: April 2023

Abstract
Background: Serum vascular adhesion protein-1 (VAP-1) predicts cancer-related mortality in diabetic subjects. However, whether serum VAP-1 predicts cancer incidence or cancer progression remains unclear. We conducted a cohort study to investigate whether serum VAP-1 and related clinical variables predict incident cancers in type II diabetic subjects.

Methods: From 1996 to 2003, we enrolled 568 type II diabetic subjects who were free of cancer at baseline. Serum VAP-1 at enrollment was measured by time-resolved immunofluorometric assay. Chronic kidney disease (CKD) was defined as estimated glomerular filtration rate <60 mL/min per 1.73 m2. The subjects were followed until first occurrence of cancer or until December 31, 2011.

Results: During a mean follow-up of 11.3 years, 71 subjects developed incident cancers. The HRs for incident cancers in subjects with highest tertile of serum VAP-1 and in subjects with CKD were 2.95 [95% confidence interval (CI), 1.31–6.63; P = 0.009] and 2.29 (95% CI, 1.18–4.44; P = 0.015), respectively, after multivariate adjustment. There was an interaction between serum VAP-1 and CKD on the risk of incident cancers (P = 0.01 for log-transformed VAP-1 × CKD). The relationship among serum VAP-1, CKD, and incident cancers was similar if death was considered in the competing risk models or if subjects with shorter follow-up period were excluded.

Conclusions: Higher serum VAP-1 and CKD can independently predict future development of cancers in type II diabetic subjects.

Impact: Physicians should be aware of the early signs of cancer in diabetic individuals with elevated VAP-1 or renal dysfunction. More aggressive treatment strategies might be considered. Cancer Epidemiol Biomarkers Prev; 23(7); 1366–73. ©2014 AACR.
Data from Comparison of Collection Methods for Fecal Samples for Discovery Metabolomics in Epidemiologic Studies
Authors: Loftfield Erikka , Vogtmann Emily , Sampson Joshua N. , Moore Steven C. , Nelson Heidi , Knight Rob , Chia Nicholas , Sinha Rashmi
Published: April 2023

Abstract
Background: The gut metabolome may be associated with the incidence and progression of numerous diseases. The composition of the gut metabolome can be captured by measuring metabolite levels in the feces. However, there are little data describing the effect of fecal sample collection methods on metabolomic measures.

Methods: We collected fecal samples from 18 volunteers using four methods: no solution, 95% ethanol, fecal occult blood test (FOBT) cards, and fecal immunochemical test (FIT). One set of samples was frozen after collection (day 0), and for 95% ethanol, FOBT, and FIT, a second set was frozen after 96 hours at room temperature. We evaluated (i) technical reproducibility within sample replicates, (ii) stability after 96 hours at room temperature for 95% ethanol, FOBT, and FIT, and (iii) concordance of metabolite measures with the putative “gold standard,” day 0 samples without solution.

Results: Intraclass correlation coefficients (ICC) estimating technical reproducibility were high for replicate samples for each collection method. ICCs estimating stability at room temperature were high for 95% ethanol and FOBT (median ICC > 0.87) but not FIT (median ICC = 0.52). Similarly, Spearman correlation coefficients (rs) estimating metabolite concordance with the “gold standard” were higher for 95% ethanol (median rs = 0.82) and FOBT (median rs = 0.70) than for FIT (median rs = 0.40).

Conclusions: Metabolomic measurements appear reproducible and stable in fecal samples collected with 95% ethanol or FOBT. Concordance with the “gold standard” is highest with 95% ethanol and acceptable with FOBT.

Impact: Future epidemiologic studies should collect feces using 95% ethanol or FOBT if interested in studying fecal metabolomics. Cancer Epidemiol Biomarkers Prev; 25(11); 1483–90. ©2016 AACR.
Data from Colorectal Cancer Screening: How Health Gains and Cost-Effectiveness Vary by Ethnic Group, the Impact on Health Inequalities, and the Optimal Age Range to Screen
Authors: McLeod Melissa , Kvizhinadze Giorgi , Boyd Matt , Barendregt Jan , Sarfati Diana , Wilson Nick , Blakely Tony
Published: April 2023

Abstract
Background: Screening programs consistently underserve indigenous populations despite a higher overall burden of cancer. In this study, we explore the likely health gains and cost-effectiveness of a national colorectal cancer screening program for the indigenous Māori population of New Zealand (NZ).

Methods: A Markov model estimated: health benefits (quality-adjusted life-year; QALY), costs, and cost-effectiveness of biennial immunochemical fecal occult blood testing (FOBTi) of 50- to 74-year-olds from 2011. Input parameters came from literature reviews, the NZ Bowel Screening Programme Pilot, and NZ linked health datasets. Equity analyses substituted non-Māori values for Māori values of background (noncolorectal cancer) morbidity and mortality, colorectal cancer survival and incidence, screening coverage, and stage-specific survival. We measured the change in “quality-adjusted life expectancy” (QALE) as a result of the intervention.

Results: Based upon a threshold of GDP per capita (NZ$45,000), colorectal cancer screening in NZ using FOBTi is cost-effective: NZ$2,930 (US$1,970) per QALY gained [95% uncertainty interval: cost saving to $6,850 (US$4,610)]. Modeled health gains per capita for Māori were less than for non-Māori: half for 50- to 54-year-olds (0.031 QALYs per person for Māori vs. 0.058 for non-Māori), and a fifth (0.003 c.f. 0.016) for 70- to 74-year-olds and ethnic inequalities in QALE increased with colorectal cancer screening.

Conclusions: Colorectal cancer screening in NZ using FOBTi is likely to be cost-effective but risks increasing inequalities in health for Māori.

Impact: To avoid or mitigate the generation of further health inequalities, attention should be given to underserved population groups when planning and implementing screening programs. Cancer Epidemiol Biomarkers Prev; 26(9); 1391–400. ©2017 AACR.
Data from Body Mass Index and Colon Cancer Screening: A Systematic Review and Meta-Analysis
Authors: Maruthur Nisa M. , Bolen Shari , Gudzune Kimberly , Brancati Frederick L. , Clark Jeanne M.
Published: April 2023

Abstract
Background: Obesity is associated with increased colon cancer mortality and lower rates of mammography and Pap testing.

Methods: We conducted a systematic review to determine whether obesity is associated with lower rates of colon cancer screening. We searched the PubMed, CINAHL, and Cochrane Library databases. Two investigators reviewed citations, abstracts, and articles independently. Two investigators abstracted study information sequentially and evaluated quality independently using standardized forms. We included all studies in our qualitative syntheses. We used random effects meta-analyses to combine those studies providing screening results by the following body mass index (BMI) categories: Normal, 18.5–24.9 kg/m2 (reference); overweight, 25–29.9 kg/m2; class I obesity, 30–34.9 kg/m2; class II obesity, 35–39.9 kg/m2; and class III obesity, ≥ 40 kg/m2.

Results: Of 5,543 citations, we included 23 articles. Almost all studies were cross-sectional and ascertained BMI and screening through self-report. BMI was not associated with colon cancer screening overall. The subgroup of obese white women reported lower rates of colon cancer screening compared with those with a normal BMI with combined ORs (95% CI) of 0.87 (0.82–0.93), 0.80 (0.65–0.99), and 0.73 (0.58–0.94) for class I, II, and III obesity, respectively. Results were similar among white men with class II obesity.

Conclusions: Overall, BMI was not associated with colon cancer screening. Obese white men and women may be less likely to undergo colon cancer screening compared with those with a normal BMI.

Impact: Further investigation of this disparity may reduce the risk of obesity-related colon cancer death. Cancer Epidemiol Biomarkers Prev; 21(5); 737–46. ©2012 AACR.
Data from Collaborative Cancer Epidemiology in the 21st Century: The Model of Cancer Consortia
Authors: Burgio Michael R. , Ioannidis John P.A. , Kaminski Brett M. , DeRycke Eric , Rogers Scott , Khoury Muin J. , Seminara Daniela
Published: April 2023

Abstract
During the last two decades, epidemiology has undergone a rapid evolution toward collaborative research. The proliferation of multi-institutional, interdisciplinary consortia has acquired particular prominence in cancer research. Herein, we describe the characteristics of a network of 49 established cancer epidemiology consortia (CEC) currently supported by the Epidemiology and Genomics Research Program (EGRP) at the National Cancer Institute (NCI). This collection represents the largest disease-based research network for collaborative cancer research established in population sciences. We describe the funding trends, geographic distribution, and areas of research focus. The CEC have been partially supported by 201 grants and yielded 3,876 publications between 1995 and 2011. We describe this output in terms of interdisciplinary collaboration and translational evolution. We discuss challenges and future opportunities in the establishment and conduct of large-scale team science within the framework of CEC, review future prospects for this approach to large-scale, interdisciplinary cancer research, and describe a model for the evolution of an integrated Network of Cancer Consortia optimally suited to address and support 21st-century epidemiology. Cancer Epidemiol Biomarkers Prev; 22(12); 2148–60. ©2013 AACR.
Data from Pathway Analysis of Genome-wide Association Study in Childhood Leukemia among Hispanics
Authors: Hsu Ling-I , Briggs Farren , Shao Xiaorong , Metayer Catherine , Wiemels Joseph L. , Chokkalingam Anand P. , Barcellos Lisa F.
Published: April 2023

Abstract
Background: The incidence of acute lymphoblastic leukemia (ALL) is nearly 20% higher among Hispanics than non-Hispanic Whites. Previous studies have shown evidence for association between risk of ALL and variation within IKZF1, ARID5B, CEBPE, CDKN2A, GATA3, and BM1-PIP4K2A genes. However, variants identified only account for <10% of the genetic risk of ALL.

Methods: We applied pathway-based analyses to genome-wide association study (GWAS) data from the California Childhood Leukemia Study to determine whether different biologic pathways were overrepresented in childhood ALL and major ALL subtypes. Furthermore, we applied causal inference and data reduction methods to prioritize candidate genes within each identified overrepresented pathway, while accounting for correlation among SNPs.

Results: Pathway analysis results indicate that different ALL subtypes may involve distinct biologic mechanisms. Focal adhesion is a shared mechanism across the different disease subtypes. For ALL, the top five overrepresented Kyoto Encyclopedia of Genes and Genomes pathways include axon guidance, protein digestion and absorption, melanogenesis, leukocyte transendothelial migration, and focal adhesion (PFDR < 0.05). Notably, these pathways are connected to downstream MAPK or Wnt signaling pathways which have been linked to B-cell malignancies. Several candidate genes for ALL, such as COL6A6 and COL5A1, were identified through targeted maximum likelihood estimation.

Conclusions: This is the first study to show distinct biologic pathways are overrepresented in different ALL subtypes using pathway-based approaches, and identified potential gene candidates using causal inference methods.

Impact: The findings demonstrate that newly developed bioinformatics tools and causal inference methods can provide insights to furthering our understanding of the pathogenesis of leukemia. Cancer Epidemiol Biomarkers Prev; 25(5); 815–22. ©2016 AACR.
Data from Coffee Consumption and the Risk of Colorectal Cancer
Authors: Schmit Stephanie L. , Rennert Hedy S. , Rennert Gad , Gruber Stephen B.
Published: April 2023

Abstract
Background: Coffee contains several bioactive compounds relevant to colon physiology. Although coffee intake is a proposed protective factor for colorectal cancer, current evidence remains inconclusive.

Methods: We investigated the association between coffee consumption and risk of colorectal cancer in 5,145 cases and 4,097 controls from the Molecular Epidemiology of Colorectal Cancer (MECC) study, a population-based case–control study in northern Israel. We also examined this association by type of coffee, by cancer site (colon and rectum), and by ethnic subgroup (Ashkenazi Jews, Sephardi Jews, and Arabs). Coffee data were collected by interview using a validated, semi-quantitative food frequency questionnaire.

Results: Coffee consumption was associated with 26% lower odds of developing colorectal cancer [OR (drinkers vs. non-drinkers), 0.74; 95% confidence interval (CI), 0.64–0.86; P < 0.001]. The inverse association was also observed for decaffeinated coffee consumption alone (OR, 0.82; 95% CI, 0.68–0.99; P = 0.04) and for boiled coffee (OR, 0.82; 95% CI, 0.71–0.94; P = 0.004). Increasing consumption of coffee was associated with lower odds of developing colorectal cancer. Compared with <1 serving/day, intake of 1 to <2 servings/day (OR, 0.78; 95% CI, 0.68–0.90; P < 0.001), 2 to 2.5 servings/day (OR, 0.59; 95% CI, 0.51–0.68; P < 0.001), and >2.5 servings/day (OR, 0.46; 95% CI, 0.39–0.54; P < 0.001) were associated with significantly lower odds of colorectal cancer (Ptrend < 0.001), and the dose–response trend was statistically significant for both colon and rectal cancers.

Conclusions: Coffee consumption may be inversely associated with risk of colorectal cancer in a dose–response manner.

Impact: Global coffee consumption patterns suggest potential health benefits of the beverage for reducing the risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev; 25(4); 634–9. ©2016 AACR.
Data from Oral Contraceptive Use and Risk of Breast, Cervical, Colorectal, and Endometrial Cancers: A Systematic Review
Authors: Gierisch Jennifer M. , Coeytaux Remy R. , Urrutia Rachel Peragallo , Havrilesky Laura J. , Moorman Patricia G. , Lowery William J. , Dinan Michaela , McBroom Amanda J. , Hasselblad Vic , Sanders Gillian D. , Myers Evan R.
Published: April 2023

Abstract
Oral contraceptives may influence the risk of certain cancers. As part of the AHRQ Evidence Report, Oral Contraceptive Use for the Primary Prevention of Ovarian Cancer, we conducted a systematic review to estimate associations between oral contraceptive use and breast, cervical, colorectal, and endometrial cancer incidence. We searched PubMed, Embase, and Cochrane Database of Systematic Reviews. Study inclusion criteria were women taking oral contraceptives for contraception or ovarian cancer prevention; includes comparison group with no oral contraceptive use; study reports quantitative associations between oral contraceptive exposure and relevant cancers; controlled study or pooled patient-level meta-analyses; sample size for nonrandomized studies ≥100; peer-reviewed, English-language; published from January 1, 2000 forward. Random-effects meta-analyses were conducted by estimating pooled ORs with 95% confidence intervals (CIs). We included 44 breast, 12 cervical, 11 colorectal, and 9 endometrial cancers studies. Breast cancer incidence was slightly but significantly increased in users (OR, 1.08; CI, 1.00–1.17); results show a higher risk associated with more recent use of oral contraceptives. Risk of cervical cancer was increased with duration of oral contraceptive use in women with human papillomavirus infection; heterogeneity prevented meta-analysis. Colorectal cancer (OR, 0.86; CI, 0.79–0.95) and endometrial cancer incidences (OR, 0.57; CI, 0.43–0.77) were significantly reduced by oral contraceptive use. Compared with never use, ever use of oral contraceptives is significantly associated with decreases in colorectal and endometrial cancers and increases in breast cancers. Although elevated breast cancer risk was small, relatively high incidence of breast cancers means that oral contraceptives may contribute to a substantial number of cases. Cancer Epidemiol Biomarkers Prev; 22(11); 1931–43. ©2013 AACR.
Data from Investigation of Metabolomic Blood Biomarkers for Detection of Adenocarcinoma Lung Cancer
Authors: Fahrmann Johannes F. , Kim Kyoungmi , DeFelice Brian C. , Taylor Sandra L. , Gandara David R. , Yoneda Ken Y. , Cooke David T. , Fiehn Oliver , Kelly Karen , Miyamoto Suzanne
Published: April 2023

Abstract
Background: Untargeted metabolomics was used in case–control studies of adenocarcinoma (ADC) lung cancer to develop and test metabolite classifiers in serum and plasma as potential biomarkers for diagnosing lung cancer.

Methods: Serum and plasma were collected and used in two independent case–control studies (ADC1 and ADC2). Controls were frequency matched for gender, age, and smoking history. There were 52 adenocarcinoma cases and 31 controls in ADC1 and 43 adenocarcinoma cases and 43 controls in ADC2. Metabolomics was conducted using gas chromatography time-of-flight mass spectrometry. Differential analysis was performed on ADC1 and the top candidates (FDR < 0.05) for serum and plasma used to develop individual and multiplex classifiers that were then tested on an independent set of serum and plasma samples (ADC2).

Results: Aspartate provided the best accuracy (81.4%) for an individual metabolite classifier in serum, whereas pyrophosphate had the best accuracy (77.9%) in plasma when independently tested. Multiplex classifiers of either 2 or 4 serum metabolites had an accuracy of 72.7% when independently tested. For plasma, a multimetabolite classifier consisting of 8 metabolites gave an accuracy of 77.3% when independently tested. Comparison of overall diagnostic performance between the two blood matrices yielded similar performances. However, serum is most ideal given higher sensitivity for low-abundant metabolites.

Conclusion: This study shows the potential of metabolite-based diagnostic tests for detection of lung adenocarcinoma. Further validation in a larger pool of samples is warranted.

Impact: These biomarkers could improve early detection and diagnosis of lung cancer. Cancer Epidemiol Biomarkers Prev; 24(11); 1716–23. ©2015 AACR.
Data from Glycemic Index, Glycemic Load, and Lung Cancer Risk in Non-Hispanic Whites
Authors: Melkonian Stephanie C. , Daniel Carrie R. , Ye Yuanqing , Pierzynski Jeanne A. , Roth Jack A. , Wu Xifeng
Published: April 2023

Abstract
Background: Postprandial glucose (PPG) and insulin responses play a role in carcinogenesis. We evaluated the association between dietary glycemic index (GI) and glycemic load (GL), markers of carbohydrate intake and PPG, and lung cancer risk in non-Hispanic whites.

Methods: GL and GI were assessed among 1,905 newly diagnosed lung cancer cases recruited from the University of Texas MD Anderson Cancer Center (Houston, TX) and 2,413 healthy controls recruited at Kelsey-Seybold Clinics (Houston, TX). We assessed associations between quintiles of GI/GL and lung cancer risk and effect modification by various risk factors. ORs and 95% confidence intervals (CI) were estimated using multivariable logistic regression.

Results: We observed a significant association between GI [5th vs. 1st quintile (Q) OR = 1.49; 95% CI, 1.21–1.83; Ptrend <0.001] and lung cancer risk and GIac (5th vs. 1st Q OR = 1.48; 95% CI, 1.20–1.81; Ptrend = 0.001) and lung cancer risk. We observed a more pronounced association between GI and lung cancer risk among never smokers (5th vs. 1st Q OR = 2.25; 95% CI, 1.42–3.57), squamous cell carcinomas (SCC; 5th vs. 1st Q OR = 1.92; 95% CI, 1.30–2.83), and those with less than 12 years of education (5th vs. 1st Q OR = 1.75; 95% CI, 1.19–2.58, Pinteraction = 0.02).

Conclusion: This study suggests that dietary GI and other lung cancer risk factors may jointly and independently influence lung cancer etiology.

Impact: Understanding the role of GI in lung cancer could inform prevention strategies and elucidate biologic pathways related to lung cancer risk. Cancer Epidemiol Biomarkers Prev; 25(3); 532–9. ©2016 AACR.
Data from BRAF Mutation Status and Survival after Colorectal Cancer Diagnosis According to Patient and Tumor Characteristics
Authors: Phipps Amanda I. , Buchanan Daniel D. , Makar Karen W. , Burnett-Hartman Andrea N. , Coghill Anna E. , Passarelli Michael N. , Baron John A. , Ahnen Dennis J. , Win Aung Ko , Potter John D. , Newcomb Polly A.
Published: April 2023

Abstract
Background:BRAF mutations in colorectal cancer (CRC) are disproportionately observed in tumors exhibiting microsatellite instability (MSI) and are associated with other prognostic factors. The independent association between BRAF mutation status and CRC survival, however, remains unclear.

Methods: We evaluated the association between the BRAF c.1799T>A (p.V600E) mutation and survival in individuals with incident invasive CRC diagnosed between 1997 and 2007 in Western Washington State. Tumor specimens were tested for this BRAF mutation and MSI status. We used Cox regression to estimate HRs and 95% confidence intervals (CI) for the association between BRAF mutation status and disease-specific and overall survival. Stratified analyses were conducted by age, sex, tumor site, stage, and MSI status.

Results: Among 1,980 cases tested, 12% were BRAF c.1799T>A (p.V600E) mutation–positive (n = 247). BRAF-mutated CRC was associated with poorer disease-specific survival adjusting for age, sex, time from diagnosis to enrollment, stage, and MSI status (HR, 1.43; 95% CI, 1.05–1.95). This association was limited to cases diagnosed at ages <50 (HR, 3.06; 95% CI, 1.70–5.52) and was not evident in cases with MSI-high tumors (HR, 0.94; 95% CI, 0.44–2.03). Associations with overall survival were similar.

Conclusions: Our results show that the prevalence of BRAF mutations in CRC differs by patient and tumor characteristics and suggest that the association between BRAF status and CRC survival may differ by some of these factors.

Impact: The presence of a BRAF c.1799T>A (p.V600E) mutation is associated with significantly poorer prognosis after CRC diagnosis among subgroups of patients. Cancer Epidemiol Biomarkers Prev; 21(10); 1792–8. ©2012 AACR.
Data from Serum Proteoglycans as Prognostic Biomarkers of Hepatocellular Carcinoma in Patients with Alcoholic Cirrhosis
Authors: Nault Jean-Charles , Guyot Erwan , Laguillier Christelle , Chevret Sylvie , Ganne-Carrie Nathalie , N'Kontchou Gisèle , Beaugrand Michel , Seror Olivier , Trinchet Jean-Claude , Coelho Jessica , Lasalle Philippe , Charnaux Nathalie , Delehedde Maryse , Sutton Angela , Nahon Pierre
Published: April 2023

Abstract
Background: Proteoglycans are involved in neoangiogenesis and transduction of oncogenic signals, two hallmarks of carcinogenesis.

Methods: This study sought to assess the prognostic value of serum levels of three proteoglycans (endocan, syndecan-1, and glypican-3) and VEGF in 295 patients with alcoholic cirrhosis: 170 without hepatocellular carcinoma, 58 with early hepatocellular carcinoma, and 67 with advanced hepatocellular carcinoma at inclusion. We analyzed the association between proteoglycan levels and prognosis using Kaplan–Meier and Cox methods.

Results: Serum levels of the three proteoglycans and VEGF were increased in patients with advanced hepatocellular carcinoma compared with those without hepatocellular carcinoma or with early hepatocellular carcinoma. In multivariate analysis, high levels of serum endocan (>5 ng/mL) were independently associated with death [HR, 2.84; 95% confidence interval (CI,) 1.18–6.84; P = 0.02], but not with hepatocellular carcinoma occurrence, in patients without hepatocellular carcinoma at baseline. High serum endocan (>5 ng/mL) and syndecan-1 (>50 ng/mL) levels were significantly associated with greater risk of tumor recurrence (P = 0.025) in patients with early hepatocellular carcinoma treated by radiofrequency ablation. In patients with advanced hepatocellular carcinoma, high serum levels of endocan (P = 0.004) and syndecan-1 (P = 0.006) were significantly associated with less favorable overall survival. However, only a high level of serum syndecan-1 (>50 ng/mL) was independently associated with greater risk of death (HR, 6.21 95% CI, 1.90–20.30; P = 0.0025).

Conclusion: Serum endocan and syndecan-1 are easily assessable prognostic serum biomarkers of overall survival in alcoholic cirrhosis with and without hepatocellular carcinoma.

Impact: These new biomarkers will be useful to manage patients with hepatocellular carcinoma developed on alcoholic cirrhosis. Cancer Epidemiol Biomarkers Prev; 22(8); 1343–52. ©2013 AACR.
Data from Circulating Biomarkers of Tryptophan and the Kynurenine Pathway and Lung Cancer Risk
Authors: Chuang Shu-Chun , Fanidi Anouar , Ueland Per Magne , Relton Caroline , Midttun Øivind , Vollset Stein Emil , Gunter Marc J. , Seckl Michael J. , Travis Ruth C. , Wareham Nicholas , Trichopoulou Antonia , Lagiou Pagona , Trichopoulos Dimitrios , Peeters Petra H.M. , Bueno-de-Mesquita H. Bas , Boeing Heiner , Wientzek Angelika , Kuehn Tilman , Kaaks Rudolf , Tumino Rosario , Agnoli Claudia , Palli Domenico , Naccarati Alessio , Aicua Eva Ardanaz , Sánchez María-José , Quirós José Ramón , Chirlaque María-Dolores , Agudo Antonio , Johansson Mikael , Grankvist Kjell , Boutron-Ruault Marie-Christine , Clavel-Chapelon Françoise , Fagherazzi Guy , Weiderpass Elisabete , Riboli Elio , Brennan Paul J. , Vineis Paolo , Johansson Mattias
Published: April 2023

Abstract
Background: Imbalances in tryptophan metabolism have been linked to cancer-related immune escape and implicated in several cancers, including lung cancer.

Methods: We conducted a nested case–control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) that included 893 incident lung cancer cases and 1,748 matched controls. Circulating levels of tryptophan and six of its metabolites were measured and evaluated in relation to lung cancer risk.

Results: Tryptophan (Ptrend = 2 × 10−5) and the kynurenine/tryptophan ratio (KTR; Ptrend = 4 × 10−5) were associated with lung cancer risk overall after adjusting for established risk factors. The ORs comparing the fifth and first quintiles (OR5th vs. 1st) were 0.52 [95% confidence interval (CI), 0.37–0.74] for tryptophan and 1.74 (95% CI, 1.24–2.45) for KTR. After adjusting for plasma methionine (available from previous work, which was strongly correlated with tryptophan), the associations of tryptophan (adjusted Ptrend = 0.13) and KTR (Ptrend = 0.009) were substantially attenuated. KTR was positively associated with squamous cell carcinoma, the OR5th vs. 1st being 2.83 (95% CI, 1.62–4.94, Ptrend = 3 × 10−5) that was only marginally affected by adjusting for methionine.

Conclusions: This study indicates that biomarkers of tryptophan metabolism are associated with subsequent lung cancer risk. Although this result would seem consistent with the immune system having a role in lung cancer development, the overall associations were dependent on methionine, and further studies are warranted to further elucidate the importance of these metabolites in lung cancer etiology.

Impact: This is the first prospective study investigating the tryptophan pathway in relation to lung cancer risk. Cancer Epidemiol Biomarkers Prev; 23(3); 461–8. ©2013 AACR.
Data from Population Distribution of Lifetime Risk of Ovarian Cancer in the United States
Authors: Pearce Celeste Leigh , Stram Daniel O. , Ness Roberta B. , Stram Douglas A. , Roman Lynda D. , Templeman Claire , Lee Alice W. , Menon Usha , Fasching Peter A. , McAlpine Jessica N. , Doherty Jennifer A. , Modugno Francesmary , Schildkraut Joellen M. , Rossing Mary Anne , Huntsman David G. , Wu Anna H. , Berchuck Andrew , Pike Malcolm C. , Pharoah Paul D.P.
Published: April 2023

Abstract
Background: In U.S. women, lifetime risk of ovarian cancer is 1.37%, but some women are at a substantially lower or higher risk than this average.

Methods: We have characterized the distribution of lifetime risk in the general population. Published data on the relative risks and their variances for five well-accepted risk and protective factors for ovarian cancer, oral contraceptive use, parity, tubal ligation, endometriosis, and first-degree family history of ovarian cancer in conjunction with a genetic risk score using genome-wide significant common, low penetrance variants were used. The joint distribution of these factors (i.e., risk/protective factor profiles) was derived using control data from four U.S. population–based studies, providing a broad representation of women in the United States.

Results: A total of 214 combinations of risk/protective factors were observed, and the lifetime risk estimates ranged from 0.35% [95% confidence interval (CI), 0.29–0.42] to 8.78% (95% CI, 7.10–10.9). Among women with lifetime risk ranging from 4% to 9%, 73% had no family history of ovarian cancer; most of these women had a self-reported history of endometriosis.

Conclusions: Profiles including the known modifiable protective factors of oral contraceptive use and tubal ligation were associated with a lower lifetime risk of ovarian cancer. Oral contraceptive use and tubal ligation were essentially absent among the women at 4% to 9% lifetime risk.

Impact: This work demonstrates that there are women in the general population who have a much higher than average lifetime risk of ovarian cancer. Preventive strategies are available. Should effective screening become available, higher than average risk women can be identified. Cancer Epidemiol Biomarkers Prev; 24(4); 671–6. ©2015 AACR.