bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplemental Tables 1-4 from Traditional Breast Cancer Risk Factors in Filipina Americans Compared with Chinese and Japanese Americans in Los Angeles County
Authors: Wu Anna H. , Vigen Cheryl , Lee Eunjung , Tseng Chiu-Chen , Butler Lesley M.
Published: April 2023

Supplemental table 1 presents reproductive factors in Filipina, Chinese, and Japanese migrants by timing of birth Supplemental table 2 presents select risk factors by tumor stage at diagnosis (in situ, localized, and advanced stage) Supplemental table 3 presents select menstrual and reproductive factors by hormone receptor status Supplemental table 4 compares interviewed and non-interviewed breast cancer cases by age, neighborhood SES, and tumor stage at diagnosis
Table S3. Primers used for pyrosequencing of HPV 16-positive samples from Targeted, Deep Sequencing Reveals Full Methylation Profiles of Multiple HPV Types and Potential Biomarkers for Cervical Cancer Progression
Authors: Liu Pengyuan , Iden Marissa , Fye Samantha , Huang Yi-Wen , Hopp Elizabeth , Chu Chen , Lu Yan , Rader Janet S.
Published: April 2023

Primer sequences used for pyrosequencing validation experiments.
Supplementary Figure S2. Probability density of proportion of mapped reads in HPV-negative samples from Targeted, Deep Sequencing Reveals Full Methylation Profiles of Multiple HPV Types and Potential Biomarkers for Cervical Cancer Progression
Authors: Liu Pengyuan , Iden Marissa , Fye Samantha , Huang Yi-Wen , Hopp Elizabeth , Chu Chen , Lu Yan , Rader Janet S.
Published: April 2023

To determine HPV types using read counts, we estimated the proportion of mapped reads of HPVs in each sample. As seen in the plot of probability density, the chance of a proportion of mapped reads in HPV-negative samples being larger than 15% is <5%. The proportion of mapped reads and their probability density in HPV-negative samples are represented by the peak on the left, while the 15% mark is denoted by the line to the right of this peak.
Supplementary Figure 3 from Biomarker Discovery for Heterogeneous Diseases
Authors: Wallstrom Garrick , Anderson Karen S. , LaBaer Joshua
Published: April 2023

PDF file - 6009K, Figure S3. Estimated power with FDR controlled at 50% for single stage design using normal samples for a (a) homogeneous disease and a (b) heterogeneous disease.
Supplementary Figure 1 from Common Genetic Variants in Prostate Cancer Risk Prediction—Results from the NCI Breast and Prostate Cancer Cohort Consortium (BPC3)
Authors: Lindström Sara , Schumacher Fredrick R. , Cox David , Travis Ruth C. , Albanes Demetrius , Allen Naomi E. , Andriole Gerald , Berndt Sonja I. , Boeing Heiner , Bueno-de-Mesquita H. Bas , Crawford E. David , Diver W. Ryan , Gaziano J. Michael , Giles Graham G. , Giovannucci Edward , Gonzalez Carlos A. , Henderson Brian , Hunter David J. , Johansson Mattias , Kolonel Laurence N. , Ma Jing , Le Marchand Loïc , Pala Valeria , Stampfer Meir , Stram Daniel O. , Thun Michael J. , Tjonneland Anne , Trichopoulos Dimitrios , Virtamo Jarmo , Weinstein Stephanie J. , Willett Walter C. , Yeager Meredith , Hayes Richard B. , Severi Gianluca , Haiman Christopher A. , Chanock Stephen J. , Kraft Peter
Published: April 2023

PDF file - 71K
Supplementary Table 1 from High Mammographic Density in Long-Term Night-Shift Workers: DDM-Spain/Var-DDM
Authors: Pedraza-Flechas Ana María , Lope Virginia , Sánchez-Contador Carmen , Santamariña Carmen , Pedraz-Pingarrón Carmen , Moreo Pilar , Ederra María , Miranda-García Josefa , Vidal Carmen , Llobet Rafael , Aragonés Nuria , Salas-Trejo Dolores , Pollán Marina , Pérez-Gómez Beatriz
Published: April 2023

Supplementary table S1. Association of current or recent (stopped NSW <1 before mammogram) Night-shift Work (NSW) and Mammographic Density in DDM-Spain/Var-DDM study.
Supplemental Tables S1-S3 from Determinants and Consequences of Arsenic Metabolism Efficiency among 4,794 Individuals: Demographics, Lifestyle, Genetics, and Toxicity
Authors: Jansen Rick J. , Argos Maria , Tong Lin , Li Jiabei , Rakibuz-Zaman Muhammad , Islam Md. Tariqul , Slavkovich Vesna , Ahmed Alauddin , Navas-Acien Ana , Parvez Faruque , Chen Yu , Gamble Mary V. , Graziano Joseph H. , Pierce Brandon L. , Ahsan Habibul
Published: April 2023

Table S1. Percentages for select baseline characteristic for 20,033 HEALS participants and subsetted based on those who have metabolite data (4794) and those who had metabolite data and were genotyped (2060). Supplemental Material, Table S2. Odds ratios and 95% confidence intervals for the association between baseline characteristics and skin lesion status (prevalent and incident (n=1,575) vs. none (n=1,780)). Supplemental Material, Table S3. Odds ratios and 95% confidence intervals for the association between quartiles of PCs and skin lesion status (prevalent+incident (n=1575) vs. none (n=1780))
Supplementary Table 1 from Distinct Genetic and Epigenetic Signatures of Colorectal Cancers According to Ethnic Origin
Authors: Nieminen Taina T. , Shoman Soheir , Eissa Saad , Peltomäki Päivi , Abdel-Rahman Wael M.
Published: April 2023

PDF file - 142K
Supplemental Table 1 from Factors Associated with False Positive Results on Screening Mammography in a Population of Predominantly Hispanic Women
Authors: McGuinness Julia E. , Ueng William , Trivedi Meghna S. , Yi Hae Seung , David Raven , Vanegas Alejandro , Vargas Jennifer , Sandoval Rossy , Kukafka Rita , Crew Katherine D.
Published: April 2023

Baseline characteristics of the Know Your Risk: Assessment at Screening (KYRAS) study sample (N=2019) compared to the remaining screened cohort not enrolled in the KYRAS study, New York, NY (November 2014-October 2015)
Data from The Association of High-Density Lipoprotein Cholesterol with Cancer Incidence in Type II Diabetes: A Case of Reverse Causality?
Authors: Morton Jamie , Ng Martin K.C. , Chalmers John , Woodward Mark , Mancia Giuseppe , Poulter Neil R. , Marre Michel , Cooper Mark E. , Zoungas Sophia
Published: April 2023

Abstract
Background: Low high-density lipoprotein cholesterol (HDL-C) and type II diabetes are associated with an increased risk for cancer. Patients with type II diabetes typically have low HDL-C; however, the association between HDL-C and cancer has not been examined in this population.

Methods: A total of 11,140 patients with type II diabetes were followed for a median of 5 years. Cox proportional hazard models were used to assess the association between baseline HDL-C and risk of cancer incidence and cancer death, with adjustments made for potential confounders. To explore the possibility of reverse causation, analyses were repeated for the cancers occurring in the first and second halves of follow-up.

Results: Six hundred and ninety-nine patients developed cancer, with 48% occurring within the first half of follow-up. For every 0.4 mmol/L lower baseline HDL-C, there was a 16% higher risk of cancer [HR 1.16; 95% confidence interval (CI), 1.06–1.28; P = 0.0008] and cancer death (HR 1.16; 95% CI, 1.01–1.32; P = 0.03). After adjustment for confounding, the higher risk remained significant for cancer (adjusted HR 1.10; 95% CI, 1.00–1.22; P = 0.05) but not for cancer death (adjusted HR 1.08; 95% CI, 0.93–1.25; P = 0.31). The association was driven by cancers occurring within the first half of follow-up (adjusted HR 1.22; 95% CI, 1.05–1.41; P = 0.008) as no significant association was found between HDL-C and cancer in the second half of follow-up.

Conclusions: Low HDL-C is associated with cancer risk in patients with type II diabetes. However, this association may be explained by confounding and reverse causation.

Impact: HDL-C is not a risk factor for cancer in type II diabetes. Cancer Epidemiol Biomarkers Prev; 22(9); 1628–33. ©2013 AACR.
Data from TLE3 Expression Is Associated with Sensitivity to Taxane Treatment in Ovarian Carcinoma
Authors: Samimi Goli , Ring Brian Z. , Ross Doug T. , Seitz Robert S. , Sutherland Robert L. , O'Brien Philippa M. , Hacker Neville F. , Huh Warner K.
Published: April 2023

Abstract
Background: We have previously shown that transducin-like enhancer of split 3 (TLE3) is associated with outcome specifically in patients with taxane-treated breast cancer and not in patients treated with anthracycline-based regimens without a taxane. The purpose of this study was to assess the association between TLE3 expression and recurrence in patients with ovarian carcinoma treated with a taxane containing regimen as opposed to those treated with a platinum-based agent alone.

Methods: We carried out immunohistochemical staining of TLE3 in two series of ovarian cancer specimens from the University of Alabama at Birmingham, Birmingham, AL and the Royal Hospital for Women, Sydney, Australia. Local and distant recurrences within the first five years of follow-up were analyzed using Kaplan–Meier, Cox proportional hazard, and multivariate analysis to assess an association between TLE3 expression and response to therapy.

Results: TLE3 was expressed in approximately 30% of tumors and expression was associated with a favorable outcome only in patients who had received taxane as part of their treatment regimen (n = 173, HR = 0.62, P = 0.012; Pinteraction = 0.024). Further analysis revealed that the predictive association between TLE3 expression and outcome was strongest in patients with nonserous histology.

Conclusion: High TLE3 expression predicts a favorable response to taxane containing chemotherapy regimens in ovarian carcinoma.

Impact: Our findings warrant an independent evaluation of TLE3 as a potential therapeutic response marker for taxane-based chemotherapy in ovarian cancer. Cancer Epidemiol Biomarkers Prev; 21(2); 273–9. ©2011 AACR.
Data from Identification of Novel Variants in Colorectal Cancer Families by High-Throughput Exome Sequencing
Authors: DeRycke Melissa S. , Gunawardena Shanaka R. , Middha Sumit , Asmann Yan W. , Schaid Daniel J. , McDonnell Shannon K. , Riska Shaun M. , Eckloff Bruce W. , Cunningham Julie M. , Fridley Brooke L. , Serie Daniel J. , Bamlet William R. , Cicek Mine S. , Jenkins Mark A. , Duggan David J. , Buchanan Daniel , Clendenning Mark , Haile Robert W. , Woods Michael O. , Gallinger Steven N. , Casey Graham , Potter John D. , Newcomb Polly A. , Le Marchand Loïc , Lindor Noralane M. , Thibodeau Stephen N. , Goode Ellen L.
Published: April 2023

Abstract
Background: Colorectal cancer (CRC) in densely affected families without Lynch Syndrome may be due to mutations in undiscovered genetic loci. Familial linkage analyses have yielded disparate results; the use of exome sequencing in coding regions may identify novel segregating variants.

Methods: We completed exome sequencing on 40 affected cases from 16 multicase pedigrees to identify novel loci. Variants shared among all sequenced cases within each family were identified and filtered to exclude common variants and single-nucleotide variants (SNV) predicted to be benign.

Results: We identified 32 nonsense or splice-site SNVs, 375 missense SNVs, 1,394 synonymous or noncoding SNVs, and 50 indels in the 16 families. Of particular interest are two validated and replicated missense variants in CENPE and KIF23, which are both located within previously reported CRC linkage regions, on chromosomes 1 and 15, respectively.

Conclusions: Whole-exome sequencing identified DNA variants in multiple genes. Additional sequencing of these genes in additional samples will further elucidate the role of variants in these regions in CRC susceptibility.

Impact: Exome sequencing of familial CRC cases can identify novel rare variants that may influence disease risk. Cancer Epidemiol Biomarkers Prev; 22(7); 1239–51. ©2013 AACR.
Data from Chronic Recreational Physical Inactivity and Epithelial Ovarian Cancer Risk: Evidence from the Ovarian Cancer Association Consortium
Authors: Cannioto Rikki , LaMonte Michael J. , Risch Harvey A. , Hong Chi-Chen , Sucheston-Campbell Lara E. , Eng Kevin H. , Brian Szender J. , Chang-Claude Jenny , Schmalfeldt Barbara , Klapdor Ruediger , Gower Emily , Minlikeeva Albina N. , Zirpoli Gary R. , Bandera Elisa V. , Berchuck Andrew , Cramer Daniel , Doherty Jennifer A. , Edwards Robert P. , Fridley Brooke L. , Goode Ellen L. , Goodman Marc T. , Hogdall Estrid , Hosono Satoyo , Jensen Allan , Jordan Susan , Kjaer Susanne K. , Matsuo Keitaro , Ness Roberta B. , Olsen Catherine M. , Olson Sara H. , Leigh Pearce Celeste , Pike Malcolm C. , Anne Rossing Mary , Szamreta Elizabeth A. , Thompson Pamela J. , Tseng Chiu-Chen , Vierkant Robert A. , Webb Penelope M. , Wentzensen Nicolas , Wicklund Kristine G. , Winham Stacey J. , Wu Anna H. , Modugno Francesmary , Schildkraut Joellen M. , Terry Kathryn L. , Kelemen Linda E. , Moysich Kirsten B.
Published: April 2023

Abstract
Background: Despite a large body of literature evaluating the association between recreational physical activity and epithelial ovarian cancer (EOC) risk, the extant evidence is inconclusive, and little is known about the independent association between recreational physical inactivity and EOC risk. We conducted a pooled analysis of nine studies from the Ovarian Cancer Association Consortium to investigate the association between chronic recreational physical inactivity and EOC risk.

Methods: In accordance with the 2008 Physical Activity Guidelines for Americans, women reporting no regular, weekly recreational physical activity were classified as inactive. Multivariable logistic regression was utilized to estimate the ORs and 95% confidence intervals (CI) for the association between inactivity and EOC risk overall and by subgroups based upon histotype, menopausal status, race, and body mass index.

Results: The current analysis included data from 8,309 EOC patients and 12,612 controls. We observed a significant positive association between inactivity and EOC risk (OR = 1.34; 95% CI, 1.14–1.57), and similar associations were observed for each histotype.

Conclusions: In this large pooled analysis examining the association between recreational physical inactivity and EOC risk, we observed consistent evidence of an association between chronic inactivity and all EOC histotypes.

Impact: These data add to the growing body of evidence suggesting that inactivity is an independent risk factor for cancer. If the apparent association between inactivity and EOC risk is substantiated, additional work via targeted interventions should be pursued to characterize the dose of activity required to mitigate the risk of this highly fatal disease. Cancer Epidemiol Biomarkers Prev; 25(7); 1114–24. ©2016 AACR.
Data from The Cumulative Risk of False-Positive Fecal Occult Blood Test after 10 Years of Colorectal Cancer Screening
Authors: Hubbard Rebecca A. , Johnson Eric , Hsia Raymond , Rutter Carolyn M.
Published: April 2023

Abstract
Background: Annual colorectal cancer screening with fecal occult blood test (FOBT) is a noninvasive alternative to screening colonoscopy once every 10 years. If false-positive FOBT results are common, then many patients selecting an FOBT regimen will be exposed to the same invasive testing as those selecting a colonoscopy regimen. The objective of this study was to estimate the probability of experiencing a false-positive after receiving annual FOBT screening for 10 years.

Methods: Medical records for patients aged 50 to 79 years receiving FOBT screening with Hemoccult Sensa between 1997 and 2009 at Group Health of Washington State captured the date and results of each FOBT, along with subsequent colorectal cancer diagnoses. We used logistic regression to analyze associations between patient characteristics and odds of a positive FOBT with no invasive cancer diagnosis within 1 year (FOBT+, CRC−). We estimated the probability of receiving at least one FOBT+, CRC− result after 10 years of screening.

Results: We observed 181,950 FOBTs from 94,637 individuals. Older patients, males, and non-White patients were significantly more likely to receive FOBT+, CRC− results (P < 0.001 for all risk factors). After 10 years of annual FOBT, 23.0% [95% confidence interval (CI), 18.2–27.0] will receive at least one FOBT+, CRC− result.

Conclusions: Most patients participating in annual FOBT screening for 10 years will not have a positive result, reinforcing the potential value of this regimen as a noninvasive alternative to colonoscopy.

Impact: Annual stool-based screening is a screening alternative resulting in substantially fewer colonoscopies than once per decade colonoscopy. Cancer Epidemiol Biomarkers Prev; 22(9); 1612–9. ©2013 AACR.
Data from Changes in Chromatin Structure in Curettage Specimens Identifies High-Risk Patients in Endometrial Cancer
Authors: Hveem Tarjei S. , Njølstad Tormund S. , Nielsen Birgitte , Syvertsen Rolf Anders , Nesheim John Arne , Kjæreng Marna L. , Kildal Wanja , Pradhan Manohar , Marcickiewicz Janusz , Tingulstad Solveig , Staff Anne C. , Haugland Hans K. , Eraker Runar , Oddenes Klaus , Rokne Jan A. , Tjugum Jostein , Lode Margaret S. , Amant Frederic , Werner Henrica M.J. , Bjørge Line , Albregtsen Fritz , Liestøl Knut , Salvesen Helga B. , Trovik Jone , Danielsen Håvard E.
Published: April 2023

Abstract
Background: Most endometrial carcinoma patients are diagnosed at an early stage with a good prognosis. However, a relatively low fraction with lethal disease constitutes a substantial number of patients due to the high incidence rate. Preoperative identification of patients with high risk and low risk for poor outcome is necessary to tailor treatment. Nucleotyping refers to characterization of cell nuclei by image cytometry, including the assessment of chromatin structure by nuclear texture analysis. This method is a strong prognostic marker in many cancers but has not been evaluated in preoperative curettage specimens from endometrial carcinoma.

Methods: The prognostic impact of changes in chromatin structure quantified with Nucleotyping was evaluated in preoperative curettage specimens from 791 endometrial carcinoma patients prospectively included in the MoMaTEC multicenter trial.

Results: Nucleotyping was an independent prognostic marker of disease-specific survival in preoperative curettage specimens among patients with Federation Internationale des Gynaecologistes et Obstetristes (FIGO) stage I–II disease (HR=2.9; 95% CI, 1.2–6.5; P = 0.013) and significantly associated with age, FIGO stage, histologic type, histologic grade, myometrial infiltration, lymph node status, curettage histology type, and DNA ploidy.

Conclusions: Nucleotyping in preoperative curettage specimens is an independent prognostic marker for disease-specific survival, with potential to supplement existing parameters for risk stratification to tailor treatment.

Impact: This is the first study to evaluate the prognostic impact of Nucleotyping in curettage specimens from endometrial carcinoma and shows that this may be a clinically useful prognostic marker in endometrial cancer. External validation is warranted. Cancer Epidemiol Biomarkers Prev; 26(1); 61–67. ©2016 AACR.
Data from Mammographic Screening and Breast Cancer Mortality: A Case–Control Study and Meta-analysis
Authors: Nickson Carolyn , Mason Kate E. , English Dallas R. , Kavanagh Anne M.
Published: April 2023

Abstract
Background: Observational studies are necessary to assess the impact of population screening on breast cancer mortality. While some ecological studies have notably found little or no association, case–control studies consistently show strong inverse associations, but they are sometimes ignored, perhaps due to theoretical biases arising from the study design. We conducted a case–control study of breast cancer deaths in Western Australia to evaluate the effect of participation in the BreastScreen Australia program, paying particular attention to potential sources of bias, and undertook an updated meta-analysis of case–control studies.

Methods: Our study included 427 cases (women who died from breast cancer), each matched to up to 10 controls. We estimated the association between screening participation and breast cancer mortality, quantifying the effect of potential sources of bias on our findings, including selection bias, information bias, and confounding. We also conducted a meta-analysis of published case–control studies.

Results: The OR for participation in the Western Australian BreastScreen program in relation to death from breast cancer was 0.48 [95% confidence interval (CI), 0.38–0.59; P < 0.001]. We were unable to identify biases that could negate this finding: sensitivity analyses generated ORs from 0.45 to 0.52. Our meta-analysis yielded an OR of 0.51 (95% CI, 0.46–0.55).

Conclusions: Our findings suggest an average 49% reduction in breast cancer mortality for women who are screened. In practice, theoretical biases have little effect on estimates from case–control studies.

Impact: Case–control studies, such as ours, provide robust and consistent evidence that screening benefits women who choose to be screened. Cancer Epidemiol Biomarkers Prev; 21(9); 1479–88. ©2012 AACR.
Data from A Novel Serum Metabolomics-Based Diagnostic Approach to Pancreatic Cancer
Authors: Kobayashi Takashi , Nishiumi Shin , Ikeda Atsuki , Yoshie Tomoo , Sakai Aya , Matsubara Atsuki , Izumi Yoshihiro , Tsumura Hidetaka , Tsuda Masahiro , Nishisaki Hogara , Hayashi Nobuhide , Kawano Seiji , Fujiwara Yutaka , Minami Hironobu , Takenawa Tadaomi , Azuma Takeshi , Yoshida Masaru
Published: April 2023

Abstract
Background: To improve the prognosis of patients with pancreatic cancer, more accurate serum diagnostic methods are required. We used serum metabolomics as a diagnostic method for pancreatic cancer.

Methods: Sera from patients with pancreatic cancer, healthy volunteers, and chronic pancreatitis were collected at multiple institutions. The pancreatic cancer and healthy volunteers were randomly allocated to the training or the validation set. All of the chronic pancreatitis cases were included in the validation set. In each study, the subjects' serum metabolites were analyzed by gas chromatography mass spectrometry (GC/MS) and a data processing system using an in-house library. The diagnostic model constructed via multiple logistic regression analysis in the training set study was evaluated on the basis of its sensitivity and specificity, and the results were confirmed by the validation set study.

Results: In the training set study, which included 43 patients with pancreatic cancer and 42 healthy volunteers, the model possessed high sensitivity (86.0%) and specificity (88.1%) for pancreatic cancer. The use of the model was confirmed in the validation set study, which included 42 pancreatic cancer, 41 healthy volunteers, and 23 chronic pancreatitis; that is, it displayed high sensitivity (71.4%) and specificity (78.1%); and furthermore, it displayed higher sensitivity (77.8%) in resectable pancreatic cancer and lower false-positive rate (17.4%) in chronic pancreatitis than conventional markers.

Conclusions: Our model possessed higher accuracy than conventional tumor markers at detecting the resectable patients with pancreatic cancer in cohort including patients with chronic pancreatitis.

Impact: It is a promising method for improving the prognosis of pancreatic cancer via its early detection and accurate discrimination from chronic pancreatitis. Cancer Epidemiol Biomarkers Prev; 22(4); 571–9. ©2013 AACR.
Data from The MTAP-CDKN2A Locus Confers Susceptibility to a Naturally Occurring Canine Cancer
Authors: Shearin Abigail L. , Hedan Benoit , Cadieu Edouard , Erich Suzanne A. , Schmidt Emmett V. , Faden Daniel L. , Cullen John , Abadie Jerome , Kwon Erika M. , Gröne Andrea , Devauchelle Patrick , Rimbault Maud , Karyadi Danielle M. , Lynch Mary , Galibert Francis , Breen Matthew , Rutteman Gerard R. , André Catherine , Parker Heidi G. , Ostrander Elaine A.
Published: April 2023

Abstract
Background: Advantages offered by canine population substructure, combined with clinical presentations similar to human disorders, makes the dog an attractive system for studies of cancer genetics. Cancers that have been difficult to study in human families or populations are of particular interest. Histiocytic sarcoma is a rare and poorly understood neoplasm in humans that occurs in 15% to 25% of Bernese Mountain Dogs (BMD).

Methods: Genomic DNA was collected from affected and unaffected BMD in North America and Europe. Both independent and combined genome-wide association studies (GWAS) were used to identify cancer-associated loci. Fine mapping and sequencing narrowed the primary locus to a single gene region.

Results: Both populations shared the same primary locus, which features a single haplotype spanning MTAP and part of CDKN2A and is present in 96% of affected BMD. The haplotype is within the region homologous to human chromosome 9p21, which has been implicated in several types of cancer.

Conclusions: We present the first GWAS for histiocytic sarcoma in any species. The data identify an associated haplotype in the highly cited tumor suppressor locus near CDKN2A. These data show the power of studying distinctive malignancies in highly predisposed dog breeds.

Impact: Here, we establish a naturally occurring model of cancer susceptibility due to CDKN2 dysregulation, thus providing insight about this cancer-associated, complex, and poorly understood genomic region. Cancer Epidemiol Biomarkers Prev; 21(7); 1019–27. ©2012 AACR.
Data from Physical Activity and Risk of Male Breast Cancer
Authors: Arem Hannah , Brinton Louise A. , Moore Steven C. , Gapstur Susan M. , Habel Laurel A. , Johnson Kenneth , Kolonel Laurence N. , McCormack Valerie A. , Michels Karin B. , Sesso Howard D. , Ursin Giske , Van Den Eeden Stephen K. , Weiderpass Elisabete , Cook Michael B. , Matthews Charles E.
Published: April 2023

Abstract
The association between leisure-time physical activity (LTPA) and male breast cancer risk is unclear. In the Male Breast Cancer Pooling Project, with 449 cases and 13,855 matched controls, we used logistic regression with study stratification to generate adjusted ORs and 95% confidence intervals (CI) for LTPA tertiles and male breast cancer risk. Compared with low LTPA, medium and high LTPA were not associated with male breast cancer risk (OR, 1.01; 95% CI, 0.79–1.29; 0.90, 0.69–1.18, respectively). In joint-effects analyses, compared with the referent of high body mass index (BMI; ≥25 kg/m2)/low LTPA, neither medium nor high PA was associated with risk among high BMI men, but normal BMI men (<25 kg/m2) with low or medium LTPA were at a nonsignificant ∼16% reduced risk and those with high LTPA were at a 27% reduced risk (OR, 0.73; 95% CI, 0.50–1.07). Physical activity alone may not confer protection against male breast cancer risk. Cancer Epidemiol Biomarkers Prev; 24(12); 1898–901. ©2015 AACR.
Data from Effects of Exercise on Insulin, IGF Axis, Adipocytokines, and Inflammatory Markers in Breast Cancer Survivors: A Systematic Review and Meta-analysis
Authors: Kang Dong-Woo , Lee Junga , Suh Sang-Hoon , Ligibel Jennifer , Courneya Kerry S. , Jeon Justin Y.
Published: April 2023

Abstract
Background: Insulin, IGF axis, adiponectin, and inflammatory markers are associated with breast cancer. Given that physical activity improves prognosis of breast cancer survivors, we investigated the effects of exercise on these markers as potential mediators between physical activity and breast cancer.

Methods: PubMed, EMBASE, CENTRAL, CINAHL, and SportDiscus were searched up to December 3, 2015, to identify randomized controlled trials (RCT) that investigated the effect of exercise on insulin, IGF axis, and cytokines in breast cancer survivors. Weighted mean difference (WMD) was calculated using either fixed- or random-effects models on the basis of the heterogeneity of the studies.

Results: A total of 18 studies involving 681 breast cancer survivors were included, and these numbers were reduced for individual biomarker analyses. We found that exercise significantly reduced fasting insulin levels [WMD, −3.46 μU/mL; 95% confidence interval (CI), −5.97 to −0.95; P = 0.007]. Furthermore, potentially meaningful but statistically nonsignificant changes were observed in insulin resistance (WMD, −0.73; 95% CI, −0.54 to 0.13; P = 0.23), adiponectin (WMD, 1.17 μg/mL; 95% CI, −0.87 to 3.20; P = 0.26), and C-reactive protein (WMD, −1.10 mg/L; 95% CI, −2.39 to 0.20; P = 0.10). Subgroup analyses showed that fasting insulin levels were significantly more impacted in studies in which intervention participants experienced a weight reduction (WMD, −7.10 μU/mL; 95% CI, −10.31 to −3.90; P < 0.001).

Conclusions: Exercise reduces fasting insulin levels in breast cancer survivors. This may be due to exercise-induced reductions in body weight.

Impact: Practitioners and clinicians may better help breast cancer prognosis be improved through exercise, anticipating physiological effects on cancer. Cancer Epidemiol Biomarkers Prev; 26(3); 355–65. ©2016 AACR.
Data from Prognostic Role of Platelet to Lymphocyte Ratio in Solid Tumors: A Systematic Review and Meta-Analysis
Authors: Templeton Arnoud J. , Ace Olga , McNamara Mairéad G. , Al-Mubarak Mustafa , Vera-Badillo Francisco E. , Hermanns Thomas , Šeruga Boštjan , Ocaña Alberto , Tannock Ian F. , Amir Eitan
Published: April 2023

Abstract
Background: Inflammation influences cancer development and progression. An elevated platelet to lymphocyte ratio (PLR), a marker of inflammation, has been linked to poor prognosis in several malignancies. Here, we quantify the prognostic impact of this biomarker.

Methods: A systematic review of databases was conducted to identify publications exploring the association of blood PLR and overall survival (OS) in solid tumors. Data were pooled in a meta-analysis. Pooled HRs for OS by disease group and by PLR cutoff groups were computed and weighted using generic inverse-variance and random-effect modeling.

Results: Twenty studies comprising 12,754 patients were assessed. Cutoffs for PLR defining risk groups ranged from 150 to 300 and were dichotomous (12 studies; group 1) or split into three groups (<150/150–300/>300, 8 studies; group 2). Higher PLR was associated with significantly worse OS in group 1 [HR = 1.87; 95% confidence interval (CI, 1.49–2.34); P < 0.001] and with a nonsignificant association in group 2 (HR per higher category = 1.21; 95%CI, 0.97–1.50; P = 0.10). The size of effect of PLR on OS was greater for metastatic disease (HR[group 1] = 2.0; 95% CI, 1.6–2.7; HR[group 2] = 1.6; 95% CI, 1.1–2.4) than for early-stage disease (HR[group 1] = 1.5; 95% CI, 1.0–2.2; HR[group 2] = 1.0; 95% CI, 0.8–1.3). A significant association was observed for colorectal, hepatocellular, gastroesophageal, ovarian, and pancreatic carcinoma in group 1 and for colorectal cancers in group 2.

Conclusion: A high PLR is associated with worse OS in various solid tumors. Further research of its regulation and relevance in daily practice is warranted.

Impact: PLR is a readily available and inexpensive biomarker with independent prognostic value in solid tumors. Cancer Epidemiol Biomarkers Prev; 23(7); 1204–12. ©2014 AACR.
Data from Transcriptomic Microenvironment of Lung Adenocarcinoma
Authors: Bossé Yohan , Sazonova Olga , Gaudreault Nathalie , Bastien Nathalie , Conti Massimo , Pagé Sylvain , Trahan Sylvain , Couture Christian , Joubert Philippe
Published: April 2023

Abstract
Background: Tissues surrounding tumors are increasingly studied to understand the biology of cancer development and identify biomarkers.

Methods: A unique geographic tissue sampling collection was obtained from patients that underwent curative lobectomy for stage I pulmonary adenocarcinoma. Tumor and nontumor lung samples located at 0, 2, 4, and 6 cm away from the tumor were collected. Whole-genome gene expression profiling was performed on all samples (n = 5 specimens × 12 patients = 60). Analyses were carried out to identify genes differentially expressed in the tumor compared with adjacent nontumor lung tissues at different distances from the tumor as well as to identify stable and transient genes in nontumor tissues with respect to tumor proximity.

Results: The magnitude of gene expression changes between tumor and nontumor sites was similar with increasing distance from the tumor. A total of 482 up- and 843 downregulated genes were found in tumors, including 312 and 566 that were consistently differentially expressed across nontumor sites. Twenty-nine genes induced and 34 knocked-down in tumors were also identified. Tumor proximity analyses revealed 15,700 stable genes in nontumor lung tissues. Gene expression changes across nontumor sites were subtle and not statistically significant.

Conclusions: This study describes the transcriptomic microenvironment of lung adenocarcinoma and adjacent nontumor lung tissues collected at standardized distances relative to the tumor.

Impact: This study provides further insights about the molecular transitions that occur from normal tissue to lung adenocarcinoma and is an important step to develop biomarkers in nonmalignant lung tissues. Cancer Epidemiol Biomarkers Prev; 26(3); 389–96. ©2016 AACR.
Data from Development and Validation of a Melanoma Risk Score Based on Pooled Data from 16 Case–Control Studies
Authors: Davies John R. , Chang Yu-mei , Bishop D. Timothy , Armstrong Bruce K. , Bataille Veronique , Bergman Wilma , Berwick Marianne , Bracci Paige M. , Elwood J. Mark , Ernstoff Marc S. , Green Adele , Gruis Nelleke A. , Holly Elizabeth A. , Ingvar Christian , Kanetsky Peter A. , Karagas Margaret R. , Lee Tim K. , Le Marchand Loïc , Mackie Rona M. , Olsson Håkan , Østerlind Anne , Rebbeck Timothy R. , Reich Kristian , Sasieni Peter , Siskind Victor , Swerdlow Anthony J. , Titus Linda , Zens Michael S. , Ziegler Andreas , Gallagher Richard P. , Barrett Jennifer H. , Newton-Bishop Julia
Published: April 2023

Abstract
Background: We report the development of a cutaneous melanoma risk algorithm based upon seven factors; hair color, skin type, family history, freckling, nevus count, number of large nevi, and history of sunburn, intended to form the basis of a self-assessment Web tool for the general public.

Methods: Predicted odds of melanoma were estimated by analyzing a pooled dataset from 16 case–control studies using logistic random coefficients models. Risk categories were defined based on the distribution of the predicted odds in the controls from these studies. Imputation was used to estimate missing data in the pooled datasets. The 30th, 60th, and 90th centiles were used to distribute individuals into four risk groups for their age, sex, and geographic location. Cross-validation was used to test the robustness of the thresholds for each group by leaving out each study one by one. Performance of the model was assessed in an independent UK case–control study dataset.

Results: Cross-validation confirmed the robustness of the threshold estimates. Cases and controls were well discriminated in the independent dataset [area under the curve, 0.75; 95% confidence interval (CI), 0.73–0.78]. Twenty-nine percent of cases were in the highest risk group compared with 7% of controls, and 43% of controls were in the lowest risk group compared with 13% of cases.

Conclusion: We have identified a composite score representing an estimate of relative risk and successfully validated this score in an independent dataset.

Impact: This score may be a useful tool to inform members of the public about their melanoma risk. Cancer Epidemiol Biomarkers Prev; 24(5); 817–24. ©2015 AACR.
Data from DNA Methylation Predicts Progression of Human Gastric Lesions
Authors: Schneider Barbara G. , Mera Robertino , Piazuelo M. Blanca , Bravo Juan C. , Zabaleta Jovanny , Delgado Alberto G. , Bravo Luis E. , Wilson Keith T. , El-Rifai Wael , Peek Richard M. , Correa Pelayo
Published: April 2023

Abstract
Background: Development of the intestinal subtype of gastric adenocarcinoma is marked by a progression of histopathologic lesions. Residents of the Andean regions of Colombia are at high risk for gastric cancer.

Methods: A cohort of 976 Colombian subjects was followed over 16 years examining effects of Helicobacter pylori eradication and treatment with antioxidants on progression of lesions. We performed methylation analysis of DNA from baseline antral biopsies from 104 subjects for whom follow-up data were available for at least 12 years. Methylation was quantitated for AMPH, CDKN2A, CDH1, EN1, EMX1, NKX6-1, PCDH10, RPRM, RSPO2, SORCS3, ZIC1, and ZNF610 genes, using Pyrosequencing.

Results: Levels of DNA methylation were associated with baseline diagnosis for AMPH, EMX1, RPRM, RSPO2, SORCS3, and ZNF610. After adjusting for baseline diagnosis and H. pylori infection, methylation levels of AMPH, PCDH10, RSPO2, and ZNF610 had progression coefficients that increased and P values that decreased over 6, 12, and 16 years. Methylation for SORCS3 was associated with progression at all 3 time points but without the continual strengthening of the effect. Scores for mononuclear leukocytes, polymorphonuclear leukocytes, or intraepithelial lymphocytes were unrelated to progression.

Conclusions: Methylation levels of AMPH, PCDH10, RSPO2, SORCS3, and ZNF610 predict progression of gastric lesions independent of the effect of duration of H. pylori infection, baseline diagnosis, gender of the patient, or scores for mononuclear leukocytes, polymorphonuclear leukocytes, or intraepithelial lymphocytes.

Impact: DNA methylation levels in AMPH, PCDH10, RSPO2, SORCS3, and ZNF610 may contribute to identification of persons with gastric lesions likely to progress. Cancer Epidemiol Biomarkers Prev; 24(10); 1607–13. ©2015 AACR.
Data from How Many Deaths from Colorectal Cancer Can Be Prevented by 2030? A Scenario-Based Quantification of Risk Factor Modification, Screening, and Treatment in Norway
Authors: Skyrud Katrine Damgaard , Myklebust Tor Åge , Bray Freddie , Eriksen Morten Tandberg , de Lange Thomas , Larsen Inger Kristin , Møller Bjørn
Published: April 2023

Abstract
Background: Colorectal cancer mortality can be reduced through risk factor modification (adherence to lifestyle recommendations), screening, and improved treatment. This study estimated the potential of these three strategies to modify colorectal cancer mortality rates in Norway.

Methods: The potential reduction in colorectal cancer mortality due to risk factor modification was estimated using the software Prevent, assuming that 50% of the population in Norway—who do not adhere to the various recommendations concerning prevention of smoking, physical activity, body weight, and intake of alcohol, red/processed meat, and fiber—started to follow the recommendations. The impact of screening was quantified assuming implementation of national flexible sigmoidoscopy screening with 50% attendance. The reduction in colorectal cancer mortality due to improved treatment was calculated assuming that 50% of the linear (positive) trend in colorectal cancer survival would continue to persist in future years.

Results: Risk factor modification would decrease colorectal cancer mortality by 11% (corresponding to 227 prevented deaths: 142 men, 85 women) by 2030. Screening and improved treatment in Norway would reduce colorectal cancer mortality by 7% (149 prevented deaths) and 12% (268 prevented deaths), respectively, by 2030. Overall, the combined effect of all three strategies would reduce colorectal cancer mortality by 27% (604 prevented deaths) by 2030.

Conclusions: Risk factor modification, screening, and treatment all have considerable potential to reduce colorectal cancer mortality by 2030, with the largest potential reduction observed for improved treatment and risk factor modification.

Impact: The estimation of these health impact measures provides useful information that can be applied in public health decision-making. Cancer Epidemiol Biomarkers Prev; 26(9); 1420–6. ©2017 AACR.
Data from Effect of Exercise on Insulin Sensitivity in Healthy Postmenopausal Women: The SHAPE Study
Authors: van Gemert Willemijn A. , Monninkhof Evelyn M. , May Anne M. , Peeters Petra H. , Schuit Albertine J.
Published: April 2023

Abstract
Background: An inactive lifestyle is a risk factor for several types of cancer. A proposed pathway through which exercise influences cancer risk is via insulin. We aim to investigate the effect of a one-year exercise intervention on insulin sensitivity, and the role of body fat in this association, in healthy, normal to overweight/obese, postmenopausal women.

Methods: In the Sex Hormones And Physical Exercise (SHAPE) study, 189 healthy, inactive and postmenopausal women [ages, 50–69 years; body mass index (BMI), 22–40 kg/m2] were randomly assigned to a one-year aerobic and strength exercise intervention (150 min/wk), or a control group. Between-group differences in fasting insulin, glucose, and homeostatic model assessment of insulin resistance (HOMA2) over time were estimated using linear mixed models.

Results: Follow-up measurements of insulin sensitivity were available for 181 (95.8%) and 182 (96.3%) women at 4 and 12 months, respectively. The intention-to-treat analysis showed no significant differences between the two study groups [treatment effect ratio of the exercise group vs. control (β; 95% confidence interval): insulin, β, 1.07 (0.96–1.19); glucose, β, 1.01 (0.99–1.02); and HOMA2, β, 1.07 (0.96–1.20)]. Similar results were found in a per protocol analysis in compliant women, and in a subgroup of women who lost >2% body fat [measured by dual-energy X-ray absorptiometry (DEXA)].

Conclusions: Participation in a one-year aerobic and strength exercise intervention program did not result in changes in insulin sensitivity in healthy postmenopausal and inactive women.

Impact: Our findings suggest that 150 min/wk of exercise, as recommended by current guidelines, is not enough to achieve improvements in insulin sensitivity and subsequent cancer risk, in healthy postmenopausal women. Cancer Epidemiol Biomarkers Prev; 24(1); 81–87. ©2014 AACR.
Data from Systematic Review of Genetic Variation in Chromosome 5p15.33 and Telomere Length as Predictive and Prognostic Biomarkers for Lung Cancer
Authors: Kachuri Linda , Latifovic Lidija , Liu Geoffrey , Hung Rayjean J.
Published: April 2023

Abstract
Lung cancer remains the leading cause of cancer mortality worldwide. Known histomolecular characteristics and genomic profiles provide limited insight into factors influencing patient outcomes. Telomere length (TL) is important for genomic integrity and has been a growing area of interest as agents targeting telomerase are being evaluated. Chromosome 5p15.33, an established cancer susceptibility locus, contains a telomerase-regulatory gene, TERT, and CLPTM1L, a gene associated with cisplatin-induced apoptosis. This review offers a summary of the clinical utility of 5p15.33 polymorphisms and TL. A total of 621 abstracts were screened, and 14 studies (7 for 5p15.33, 7 for TL) were reviewed. Endpoints included overall survival (OS), progression-free survival (PFS), therapy response, and toxicity. Of the 23 genetic variants identified, significant associations with OS and/or PFS were reported for rs401681 (CLPTM1L), rs4975616 (TERT-CLPTM1L), and rs2736109 (TERT). Both shorter and longer TL, in tumor and blood, was linked to OS and PFS. Overall, consistent evidence across multiple studies of 5p15.33 polymorphisms and TL was lacking. Despite the potential to become useful prognostic biomarkers in lung cancer, the limited number of reports and their methodologic limitations highlight the need for larger, carefully designed studies with clinically defined subpopulations and higher resolution genetic analyses. Cancer Epidemiol Biomarkers Prev; 25(12); 1537–49. ©2016 AACR.
Data from Dietary Heterocyclic Amine Intake, NAT2 Genetic Polymorphism, and Colorectal Adenoma Risk: The Colorectal Adenoma Study in Tokyo
Authors: Budhathoki Sanjeev , Iwasaki Motoki , Yamaji Taiki , Sasazuki Shizuka , Takachi Ribeka , Sakamoto Hiromi , Yoshida Teruhiko , Tsugane Shoichiro
Published: April 2023

Abstract
Background: While several studies have provided support for a positive association between meat intake and colorectal neoplasia, the role of heterocyclic amines (HCA), which is hypothesized to underline this relation, has been less consistent. We evaluated the association of HCA intake with colorectal adenoma risk in a case–control study in a middle-aged Japanese population.

Methods: Study subjects were 738 patients with adenoma and 697 controls who underwent total colonoscopy between 2004 and 2005 and responded to self-administered lifestyle and dietary questionnaires. HCA exposure concentration was estimated from meat and fish intake based on an HCA database that was validated against 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) values measured in human hair. Logistic regression models were used to estimate ORs and 95% confidence interval (CI) for the association between HCA and colorectal adenoma risk after adjusting for potential confounders.

Results: High intake of 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) and total HCA was associated with an increased risk of colorectal adenoma in women but not in men. The multivariate-adjusted OR for the highest versus lowest quartile in women was 2.10 (95% CI, 1.20–3.67; Ptrend = 0.01) for MeIQ and 1.73 (95% CI, 0.99–3.01; Ptrend = 0.03) for total HCA. No clear association with PhIP or 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) estimates and no effect modification by NAT2 acetylation genotype was observed.

Conclusions: This study suggests that high MeIQ and total HCA estimates are positively associated with colorectal adenoma risk.

Impact: The findings add to evidence that HCA may play a role in colorectal carcinogenesis in humans. Cancer Epidemiol Biomarkers Prev; 24(3); 613–20. ©2015 AACR.
Data from A Decade of GWAS Results in Lung Cancer
Authors: Bossé Yohan , Amos Christopher I.
Published: April 2023

Abstract
Genome-wide association studies (GWAS) were successful to identify genetic factors robustly associated with lung cancer. This review aims to synthesize the literature in this field and accelerate the translation of GWAS discoveries into results that are closer to clinical applications. A chronologic presentation of published GWAS on lung cancer susceptibility, survival, and response to treatment is presented. The most important results are tabulated to provide a concise overview in one read. GWAS have reported 45 lung cancer susceptibility loci with varying strength of evidence and highlighted suspected causal genes at each locus. Some genetic risk loci have been refined to more homogeneous subgroups of lung cancer patients in terms of histologic subtypes, smoking status, gender, and ethnicity. Overall, these discoveries are an important step for future development of new therapeutic targets and biomarkers to personalize and improve the quality of care for patients. GWAS results are on the edge of offering new tools for targeted screening in high-risk individuals, but more research is needed if GWAS are to pay off the investment. Complementary genomic datasets and functional studies are needed to refine the underlying molecular mechanisms of lung cancer preliminarily revealed by GWAS and reach results that are medically actionable. Cancer Epidemiol Biomarkers Prev; 27(4); 363–79. ©2018 AACR.

See all articles in this CEBP Focus section, “Genome-Wide Association Studies in Cancer.”