bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from Developing the WCRF International/University of Bristol Methodology for Identifying and Carrying Out Systematic Reviews of Mechanisms of Exposure–Cancer Associations
Authors: Lewis Sarah J. , Gardner Mike , Higgins Julian , Holly Jeff M.P. , Gaunt Tom R. , Perks Claire M. , Turner Suzanne D. , Rinaldi Sabina , Thomas Steve , Harrison Sean , Lennon Rosie J. , Tan Vanessa , Borwick Cath , Emmett Pauline , Jeffreys Mona , Northstone Kate , Mitrou Giota , Wiseman Martin , Thompson Rachel , Martin Richard M.
Published: April 2023

Abstract
Background: Human, animal, and cell experimental studies; human biomarker studies; and genetic studies complement epidemiologic findings and can offer insights into biological plausibility and pathways between exposure and disease, but methods for synthesizing such studies are lacking. We, therefore, developed a methodology for identifying mechanisms and carrying out systematic reviews of mechanistic studies that underpin exposure–cancer associations.

Methods: A multidisciplinary team with expertise in informatics, statistics, epidemiology, systematic reviews, cancer biology, and nutrition was assembled. Five 1-day workshops were held to brainstorm ideas; in the intervening periods we carried out searches and applied our methods to a case study to test our ideas.

Results: We have developed a two-stage framework, the first stage of which is designed to identify mechanisms underpinning a specific exposure–disease relationship; the second stage is a targeted systematic review of studies on a specific mechanism. As part of the methodology, we also developed an online tool for text mining for mechanism prioritization (TeMMPo) and a new graph for displaying related but heterogeneous data from epidemiologic studies (the Albatross plot).

Conclusions: We have developed novel tools for identifying mechanisms and carrying out systematic reviews of mechanistic studies of exposure–disease relationships. In doing so, we have outlined how we have overcome the challenges that we faced and provided researchers with practical guides for conducting mechanistic systematic reviews.

Impact: The aforementioned methodology and tools will allow potential mechanisms to be identified and the strength of the evidence underlying a particular mechanism to be assessed. Cancer Epidemiol Biomarkers Prev; 26(11); 1667–75. ©2017 AACR.
Data from Heme Iron Intake, Dietary Antioxidant Capacity, and Risk of Colorectal Adenomas in a Large Cohort Study of French Women
Authors: Bastide Nadia , Morois Sophie , Cadeau Claire , Kangas Suvi , Serafini Mauro , Gusto Gaëlle , Dossus Laure , Pierre Fabrice H. , Clavel-Chapelon Françoise , Boutron-Ruault Marie-Christine
Published: April 2023

Abstract
Background: Nitrosylated and non-nitrosylated heme iron from red processed and nonprocessed meat have been associated with increased colorectal carcinogenesis. Mechanisms include oxidative processes. It has been hypothesized that dietary antioxidants could counteract the effects of heme iron. We investigated the relationships between heme iron intake and the risk of colorectal adenomas, and a potential interaction with the dietary antioxidant capacity, in the E3N prospective cohort study.

Methods: The study included 17,397 women, who underwent at least one colonoscopy. Among them, 1,409 were diagnosed with at least one first colorectal adenoma during the 103,253 person-years of follow-up. Dietary intake was measured by a semiquantitative food history questionnaire. HR estimates and 95% confidence intervals (CI) were obtained from Cox proportional hazards models, adjusted for potential confounders.

Results: Heme iron intake was positively associated with colorectal and colon adenoma risks [HR for the fourth vs. first quartile: HR4 = 1.36 (1.13–1.65), Ptrend = 0.001 and HR4 = 1.49; 95% CI, 1.19–1.87; Ptrend = 0.0003, respectively]. Nonnitrosylated and nitrosylated heme iron intakes were, respectively, associated with advanced distal and proximal adenoma risks. There was a dose–effect relationship between the heme iron to total dietary antioxidant capacity ratio and colorectal adenoma risk.

Conclusion: In this prospective cohort study, the association between heme iron and colorectal adenoma risk was found to depend on site, nitrosylation or not, and the ratio with the NEAC.

Impact: These results emphasize the need for a global assessment of diet when considering nutritional prevention of colorectal carcinogenesis. Cancer Epidemiol Biomarkers Prev; 25(4); 640–7. ©2016 AACR.
Data from Genetic Variation Associated with Longer Telomere Length Increases Risk of Chronic Lymphocytic Leukemia
Authors: Ojha Juhi , Codd Veryan , Nelson Christopher P. , Samani Nilesh J. , Smirnov Ivan V. , Madsen Nils R. , Hansen Helen M. , de Smith Adam J. , Bracci Paige M. , Wiencke John K. , Wrensch Margaret R. , Wiemels Joseph L. , Walsh Kyle M.
Published: April 2023

Abstract
Background: Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world. Shorter mean telomere length in leukemic cells has been associated with more aggressive disease. Germline polymorphisms in telomere maintenance genes affect telomere length and may contribute to CLL susceptibility.

Methods: We collected genome-wide data from two groups of patients with CLL (N = 273) and two control populations (N = 5,725). In ancestry-adjusted case–control comparisons, we analyzed eight SNPs in genes definitively associated with inter-individual variation in leukocyte telomere length (LTL) in prior genome-wide association studies: ACYP2, TERC, NAF1, TERT, OBFC1, CTC1, ZNF208, and RTEL1.

Results: Three of the eight LTL-associated SNPs were associated with CLL risk at P < 0.05, including those near: TERC [OR, 1.46; 95% confidence interval (CI), 1.15–1.86; P = 1.8 × 10−3], TERT (OR = 1.23; 95% CI, 1.02–1.48; P = 0.030), and OBFC1 (OR, 1.36; 95% CI, 1.08–1.71; P = 9.6 × 10−3). Using a weighted linear combination of the eight LTL-associated SNPs, we observed that CLL patients were predisposed to longer LTL than controls in both case–control sets (P = 9.4 × 10−4 and 0.032, respectively). CLL risk increased monotonically with increasing quintiles of the weighted linear combination.

Conclusions: Genetic variants in TERC, TERT, and OBFC1 are associated with both longer LTL and increased CLL risk. Because the human CST complex competes with shelterin for telomeric DNA, future work should explore the role of OBFC1 and other CST complex genes in leukemogenesis.

Impact: A genetic predisposition to longer telomere length is associated with an increased risk of CLL, suggesting that the role of telomere length in CLL etiology may be distinct from its role in disease progression. Cancer Epidemiol Biomarkers Prev; 25(7); 1043–9. ©2016 AACR.
Data from Replication and Heritability of Prostate Cancer Risk Variants: Impact of Population-Specific Factors
Authors: Virlogeux Victor , Graff Rebecca E. , Hoffmann Thomas J. , Witte John S.
Published: April 2023

Abstract
Background: Prostate cancer incidence and mortality rates vary across populations, with African American men exhibiting the highest rates. To date, genome-wide association studies have identified 104 SNPs independently associated with prostate cancer in men of European ancestry.

Methods: We investigated whether the ability to replicate findings for these 104 SNPs in African American, Asian, and Latino populations depends on variation in risk allele frequencies (RAF), strength of associations, and/or patterns of linkage disequilibrium (LD) at the associated loci. We extracted estimates of effect from the literature, and determined RAF and LD information across the populations from the 1000 Genomes Project.

Results: Risk variants were largely replicated across populations. Relative to Europeans, 83% had smaller effect sizes among African Americans and 73% demonstrated smaller effect sizes among Latinos. Among Asians, however, 56% showed larger effect sizes than among Europeans. The largest difference in RAFs was observed between European and African ancestry populations, but this difference did not impact our ability to replicate. The extent of LD within 250 kb of risk loci in Asian ancestry populations was suggestively lower for variants that did not replicate (P = 0.013).

Conclusions: Despite substantial overlap in prostate cancer risk SNPs across populations, the variation in prostate cancer incidence among different populations may still in part reflect unique underlying genetic architectures.

Impact: Studying different ancestral populations is crucial for deciphering the genetic basis of prostate cancer. Cancer Epidemiol Biomarkers Prev; 24(6); 938–43. ©2015 AACR.
Data from Metabolic Phenotype and Risk of Colorectal Cancer in Normal-Weight Postmenopausal Women
Authors: Liang Xiaoyun , Margolis Karen L. , Hendryx Michael , Rohan Thomas E. , Groessl Erik J. , Thomson Cynthia A. , Kroenke Candyce H. , Simon Michael S. , Lane Dorothy , Stefanick Marcia , Luo Juhua
Published: April 2023

Abstract
Background: The prevalence of metabolically unhealthy phenotype in normal-weight adults is 30%, and few studies have explored the association between metabolic phenotype and colorectal cancer incidence in normal-weight individuals. Our aim was to compare the risk of colorectal cancer in normal-weight postmenopausal women who were characterized by either the metabolically healthy phenotype or the metabolically unhealthy phenotype.

Methods: A large prospective cohort, the Women's Health Initiative, was used. The analytic sample included 5,068 postmenopausal women with BMI 18.5 to <25 kg/m2. Metabolic phenotype was defined using the Adult Treatment Panel-III definition, excluding waist circumference; therefore, women with one or none of the four components (elevated triglycerides, low high-density lipoprotein cholesterol, elevated blood pressure, and elevated fasting glucose) were classified as metabolically healthy. Multivariable Cox proportional hazards regression was used to estimate adjusted HRs for the association between metabolic phenotype and risk of colorectal cancer.

Results: Among normal-weight women, those who were metabolically unhealthy had higher risks of colorectal cancer (HR, 1.49; 95% CI, 1.02–2.18) compared with those who were metabolically healthy.

Conclusions: A metabolically unhealthy phenotype was associated with higher risk of colorectal cancer among normal-weight women.

Impact: Normal-weight women should still be evaluated for metabolic health and appropriate steps taken to reduce their risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev; 26(2); 155–61. ©2017 AACR.
Data from N-acetyltransferase 2 Phenotype, Occupation, and Bladder Cancer Risk: Results from the EPIC Cohort
Authors: Pesch Beate , Gawrych Katarzyna , Rabstein Sylvia , Weiss Tobias , Casjens Swaantje , Rihs Hans-Peter , Ding Hui , Angerer Jürgen , Illig Thomas , Klopp Norman , Bueno-de-Mesquita Bas , Ros Martine M. , Kaaks Rudolf , Chang-Claude Jenny , Roswall Nina , Tjønneland Anne , Overvad Kim , Clavel-Chapelon Françoise , Boutron-Ruault Marie-Christine , Dossus Laure , Boeing Heiner , Weikert Steffen , Trichopoulos Dimitrios , Palli Domenico , Sieri Sabina , Tumino Rosario , Panico Salvatore , Quirós José Ramón , González Carlos , Sánchez Mariá José , Dorronsoro Miren , Navarro Carmen , Barricarte Aurelio , Ljungberg Börje , Johansson Mattias , Ulmert David , Ehrnström Roy , Khaw Kay-Tee , Wareham Nick , Key Timothy J. , Ferrari Pietro , Romieu Isabelle , Riboli Elio , Brüning Thomas , Vineis Paolo
Published: April 2023

Abstract
Background: An association between N-acetyltransferase 2 (NAT2) slow acetylation and bladder cancer has been consistently observed in epidemiologic studies. However, evidence has been mainly derived from case–control studies and was sparse from cohort studies. We evaluated the association between NAT2 slow acetylation and bladder cancer in a case–control study nested in the European Prospective Investigation into Cancer and Nutrition.

Methods: Exposure to aromatic amines and polycyclic aromatic hydrocarbons (PAH) could be assessed for 754 cases and 833 controls for whom occupational information was documented. A semiquantitative job-exposure matrix was applied to at-risk occupations to estimate the exposure as low, medium, or high based on tertiles of the distribution of the exposure score in controls. Using a comprehensive genotyping, NAT2 acetylation status could be categorized from 6-single-nucleotide polymorphism genotypes as slow or fast in 607 cases and 695 controls with DNA from archived blood samples.

Results: Occupational exposure to aromatic amines and PAH was associated with an increased bladder cancer risk [upper tertile of the distribution of the exposure score: OR = 1.37; 95% confidence interval (CI), 1.02–1.84, and OR = 1.50; 95% CI, 1.09–2.05, respectively]. NAT2 slow acetylation did not modify these risk estimates and was not itself associated with bladder cancer risk (OR = 1.02; 95% CI, 0.81–1.29).

Conclusions: These findings confirm established or suspected occupational risk factors but not the anticipated role of NAT2 slow acetylation in bladder cancer. No interaction was detected between NAT2 and any exposure of interest, including smoking.

Impact: Genetic testing for NAT2 would be inappropriate in occupational settings. Cancer Epidemiol Biomarkers Prev; 22(11); 2055–65. ©2013 AACR.
Data from Age-Specific Effectiveness of the Finnish Cervical Cancer Screening Programme
Authors: Lönnberg Stefan , Anttila Ahti , Luostarinen Tapio , Nieminen Pekka
Published: April 2023

Abstract
Background: There is currently some uncertainty about the effectiveness of screening outside the established core ages of 30 to 60. We audited the screening histories of cervical cancers and conducted a case–control evaluation of the effectiveness of organized screening in different ages.

Methods: Screening histories for 1,546 cervical cancer cases and 9,276 age-matched controls were derived by linkage to the screening register. ORs and 95% confidence intervals (CI) for the association of participation in a program screen and cervical cancer diagnosis in the following screening interval were estimated using conditional logistic regression and corrected for self-selection bias.

Results: Participation in a single screen was associated with a 47% decrease in cervical cancers, but this effect was age-dependent. Screening at 25 showed little or no impact on the risk of cervical cancer in the next interval, whereas screens at 40 to 65 showed protective effects of 51% to 66%.

Conclusions: Program screening at the age of 25 is not associated with a reduced risk of cervical cancer in the following screening interval. Additional analyses are needed that also take opportunistic screening of women during the first rounds of organized screening into consideration. In contrast, screening yields substantial risk reductions in older ages at least up to the age of 60. This study also provides moderate indication of a long-lasting risk reduction associated with screening at the age of 65.

Impact: Cervical cancer screening effectiveness is for the first time evaluated at different ages up to 65 with correction for self-selection bias of participation in organized screening. Cancer Epidemiol Biomarkers Prev; 21(8); 1354–61. ©2012 AACR.
Data from Risk Factors for Early Childhood Infection of Human Herpesvirus-8 in Zambian Children: The Role of Early Childhood Feeding Practices
Authors: Crabtree Kay L. , Wojcicki Janet M. , Minhas Veenu , Smith David R. , Kankasa Chipepo , Mitchell Charles D. , Wood Charles
Published: April 2023

Abstract
Background: Human herpesvirus-8 (HHV-8) infection in early childhood is common throughout sub-Saharan Africa with prevalence increasing throughout childhood. Specific routes of transmission have not been clearly delineated, though HHV-8 is present in high concentrations in saliva.

Methods: To understand the horizontal transmission of HHV-8 within households to children, we enrolled for cross-sectional analysis, 251 households including 254 children, age two and under, in Lusaka, Zambia. For all children, plasma was screened for HHV-8 and HIV type I (HIV-1) and health and behavioral questionnaires were completed. Multilevel logistic regression analysis was conducted to assess independent factors for HHV-8 infection in children.

Results: Risk factors for HHV-8 infection included increasing number of HHV-8–positive household members [OR = 2.5; 95% confidence interval (CI), 1.9–3.3; P < 0.01] and having a primary caregiver who tested the temperature of food with their tongue before feeding the child (OR = 2.4; 95% CI, 1.93–3.30; P = 0.01). Breastfeeding was protective against infection with HHV-8 for children (OR = 0.3; 95% CI, 0.16–0.72; P < 0.01).

Conclusions: These results indicate that exposure to HHV-8 in the household increases risk for early childhood infection, with specific feeding behaviors likely playing a role in transmission.

Impact: Interventions to protect children from infection should emphasize the possibility of infection through sharing of foods. Cancer Epidemiol Biomarkers Prev; 23(2); 300–8. ©2013 AACR.
Data from Risk of Colorectal Cancer in Patients with Acute Myocardial Infarction and Stroke: A Nationwide Cohort Study
Authors: Erichsen Rune , Sværke Claus , Sørensen Henrik T. , Sandler Robert S. , Baron John A.
Published: April 2023

Abstract
Background: An association between colorectal cancer and acute myocardial infarction (AMI) and stroke has been suggested, but evidence is conflicting.

Method: We conducted a population-based cohort study (1978–2010) of the association between AMI/stroke and colorectal cancer by linking nationwide Danish registries. We calculated standardized incidence ratios (SIR) of colorectal cancer after AMI/stroke as the ratios of observed to expected incidence.

Results: A total of 297,523 patients with AMI (median age, 69.4 years; 64% men) were followed for a median of 3.1 years (range, 0–33 years) and 4,387 developed colorectal cancer [SIR, 1.08; 95% confidence interval (CI), 1.05–1.11; P < 0.001]. In the first year of follow-up, the SIR was 1.85 (95% CI, 1.73–1.98; P < 0.001), whereas it was 0.98 (95% CI, 0.95–1.02; P = 0.318) in the second and subsequent years. We followed 246,998 patients with stroke (median age, 72.4 years; 52% men) for a median of 2.9 years (range, 0–33 years) and 3,035 developed colorectal cancer (SIR, 1.04; 95% CI, 1.00–1.07; P = 0.053). In the first year of follow-up, the SIR was 1.42 (95% CI, 1.31–1.53; P < 0.001), whereas it was 0.96 (95% CI, 0.93–1.00; P = 0.072) thereafter. We found no difference between the SIRs for ischemic and hemorrhagic stroke. The increased one-year relative risks for AMI and stroke corresponded to a 0.3% absolute risk.

Conclusions: Our findings reflect detection of occult cancer at the time of the vascular event. The lack of increased risk after one year suggests that an association based on shared risk factors or chronic inflammation is unlikely.

Impact: In patients with AMI/stroke, the diagnostic workup including screening for colorectal cancer should follow that of the general population. Cancer Epidemiol Biomarkers Prev; 22(11); 1994–9. ©2013 AACR.
Data from Age-Period-Cohort Analysis of Primary Bone Cancer Incidence Rates in the United States (1976–2005)
Authors: Anfinsen Kristin P. , Devesa Susan S. , Bray Freddie , Troisi Rebecca , Jonasdottir Thora J. , Bruland Oyvind S. , Grotmol Tom
Published: April 2023

Abstract
Background: Primary bone cancer comprises three major histologic types: osteosarcoma (OS), Ewing sarcoma (ES), and chondrosarcoma (CS). Given the limited knowledge about the etiology of primary bone cancer, we undertook an age-period-cohort (APC) analysis to determine whether incidence varied by birth cohort or calendar period. The purpose was to examine the temporal development of each bone cancer type and generate etiologic hypotheses via the observed birth cohort-related changes.

Methods: An APC model was fitted to incidence data for U.S. whites for OS, ES, and CS obtained from nine registries of the Surveillance, Epidemiology, and End Results program, which covers about 10% of the U.S. population, 1976–2005.

Results: The incidence of OS decreased between 1976 and 2005 among those aged over 60 years, a decline that occurred among patients with OS as their primary malignancy only. From 1986–1995 to 1996–2005, the incidence rate of CS among females of 20 to 69 years rose by about 50%, with rates increasing among consecutive cohorts born during 1935–1975. CS rates among males were stable, as were rates of ES.

Conclusion: The risk reduction in OS as a primary malignancy at older ages could possibly be related to diminished exposure over time to bone-seeking radionuclides. The CS increase among females corresponds to birth cohorts with rising exposures to oral contraceptives and menopausal hormonal therapy.

Impact: As the estrogen signaling pathway has been shown to stimulate proliferation of normal and malignant chondrocytes, estrogen exposure may increase the risk for CS. Further studies are warranted to clarify its possible etiological significance. Cancer Epidemiol Biomarkers Prev; 20(8); 1770–7. ©2011 AACR.
Data from A Pooled Analysis of Alcohol Consumption and Risk of Multiple Myeloma in the International Multiple Myeloma Consortium
Authors: Andreotti Gabriella , Birmann Brenda , De Roos Anneclaire J. , Spinelli John , Cozen Wendy , Camp Nicola J. , Moysich Kirsten , Chiu Brian , Steplowski Emily , Krzystan Joseph , Boffetta Paolo , Benhaim-Luzon Véronique , Brennan Paul , de Sanjosé Silvia , Costas Laura , Costantini Adele Seniori , Miligi Lucia , Cocco Pierluigi , Becker Nikolaus , Foretová Lenka , Maynadié Marc , Nieters Alexandra , Staines Anthony , Tricot Guido , Milliken Kevin , Weisenburger Dennis , Zheng Tongzhang , Baris Dalsu , Purdue Mark P.
Published: April 2023

Abstract
Background: Recent findings suggest that alcohol consumption may reduce risk of multiple myeloma.

Methods: To better understand this relationship, we conducted an analysis of six case–control studies participating in the International Multiple Myeloma Consortium (1,567 cases, 7,296 controls). Summary ORs and 95% confidence intervals (CI) relating different measures of alcohol consumption and multiple myeloma risk were computed by unconditional logistic regression with adjustment for age, race, and study center.

Results: Cases were significantly less likely than controls to report ever drinking alcohol (men: OR = 0.72; 95% CI, 0.59–0.89; women: OR = 0.81; 95% CI, 0.68–0.95). The inverse association with multiple myeloma was stronger when comparing current to never drinkers (men: OR = 0.57; 95% CI, 0.45–0.72; women: OR = 0.55; 95% CI, 0.45–0.68), but null among former drinkers. We did not observe an exposure–response relationship with increasing alcohol frequency, duration, or cumulative lifetime consumption. Additional adjustment for body mass index, education, or smoking did not affect our results; and the patterns of association were similar for each type of alcohol beverage examined.

Conclusions: Our study is, to our knowledge, the largest of its kind to date, and our findings suggest that alcohol consumption may be associated with reduced risk of multiple myeloma.

Impact: Prospective studies, especially those conducted as pooled analyses with large sample sizes, are needed to confirm our findings and further explore whether alcohol consumption provides true biologic protection against this rare, highly fatal malignancy. Cancer Epidemiol Biomarkers Prev; 22(9); 1620–7. ©2013 AACR.
Data from The Ability of Plasma Cotinine to Predict Nicotine and Carcinogen Exposure is Altered by Differences in CYP2A6: the Influence of Genetics, Race, and Sex
Authors: Zhu Andy Z.X. , Renner Caroline C. , Hatsukami Dorothy K. , Swan Gary E. , Lerman Caryn , Benowitz Neal L. , Tyndale Rachel F.
Published: April 2023

Abstract
Background: Cotinine, a nicotine metabolite, is a biomarker of tobacco, nicotine, and carcinogen exposure. However, a given cotinine level may not represent the same tobacco exposure; for example, African-Americans have higher cotinine levels than Caucasians after controlling for exposure.

Methods: Cotinine levels are determined by the amount of cotinine formation and the rate of cotinine removal, which are both mediated by the enzyme CYP2A6. Because CYP2A6 activity differs by sex (estrogen induces CYP2A6) and genotype, their effect on cotinine formation and removal was measured in nonsmoking Caucasians (Study 1, n = 181) infused with labeled nicotine and cotinine. The findings were then extended to ad libitum smokers (Study 2, n = 163).

Results: Study 1: Reduced CYP2A6 activity altered cotinine formation less than cotinine removal resulting in ratios of formation to removal of 1.31 and 1.12 in CYP2A6 reduced and normal metabolizers (P = 0.01), or 1.39 and 1.12 in males and females (P = 0.001), suggesting an overestimation of tobacco exposure in slower metabolizers. Study 2: Cotinine again overestimated tobacco and carcinogen exposure by 25% or more in CYP2A6 reduced metabolizers (≈2-fold between some genotypes) and in males.

Conclusions: In people with slower relative to faster CYP2A6 activity, cotinine accumulates resulting in substantial differences in cotinine levels for a given tobacco exposure.

Impact: Cotinine levels may be misleading when comparing those with differing CYP2A6 genotypes within a race, between races with differing frequencies of CYP2A6 gene variants (i.e., African-Americans have higher frequencies of reduced function variants contributing to their higher cotinine levels), or between the sexes. Cancer Epidemiol Biomarkers Prev; 22(4); 708–18. ©2013 AACR.
Data from Prior Autoimmune Disease and Risk of Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma: A Systematic Review
Authors: McShane Charlene M. , Murray Liam J. , Landgren Ola , O'Rorke Michael A. , Korde Neha , Kunzmann Andrew T. , Ismail Mohammad Roshidi , Anderson Lesley A.
Published: April 2023

Abstract
Background: Several observational studies have investigated autoimmune disease and subsequent risk of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma. Findings have been largely inconsistent and hindered by the rarity and heterogeneity of the autoimmune disorders investigated. A systematic review of the literature was undertaken to evaluate the strength of the evidence linking prior autoimmune disease and risk of MGUS/multiple myeloma.

Methods: A broad search strategy using key terms for MGUS, multiple myeloma, and 50 autoimmune diseases was used to search four electronic databases (PubMed, Medline, Embase, and Web of Science) from inception through November 2011.

Results: A total of 52 studies met the inclusion criteria, of which 32 were suitably comparable to perform a meta-analysis. “Any autoimmune disorder” was associated with an increased risk of both MGUS [n = 760 patients; pooled relative risk (RR) 1.42; 95% confidence interval (CI), 1.14–1.75] and multiple myeloma (n>2,530 patients; RR 1.13, 95% CI, 1.04–1.22). This risk was disease dependent with only pernicious anemia showing an increased risk of both MGUS (RR 1.67; 95% CI, 1.21–2.31) and multiple myeloma (RR 1.50; 95% CI, 1.25–1.80).

Conclusions: Our findings, based on the largest number of autoimmune disorders and patients with MGUS/multiple myeloma reported to date, suggest that autoimmune diseases and/or their treatment may be important in the etiology of MGUS/multiple myeloma. The strong associations observed for pernicious anemia suggest that anemia seen in plasma cell dyscrasias may be of autoimmune origin.

Impact: Underlying mechanisms of autoimmune diseases, general immune dysfunction, and/or treatment of autoimmune diseases may be important in the pathogenesis of MGUS/multiple myeloma. Cancer Epidemiol Biomarkers Prev; 23(2); 332–42. ©2014 AACR.
Data from The Cost-Effectiveness of Cervical Self-Sampling to Improve Routine Cervical Cancer Screening: The Importance of Respondent Screening History and Compliance
Authors: Burger Emily A. , Sy Stephen , Nygård Mari , Kim Jane J.
Published: April 2023

Abstract
Background: Human papillomavirus (HPV) testing allows women to self-collect cervico-vaginal cells at home (i.e., self-sampling). Using primary data from a randomized pilot study, we evaluated the long-term consequences and cost-effectiveness of using self-sampling to improve participation to routine cervical cancer screening in Norway.

Methods: We compared a strategy reflecting screening participation (using reminder letters) to strategies that involved mailing self-sampling device kits to women noncompliant to screening within a 5- or 10-year period under two scenarios: (A) self-sampling respondents had moderate under-screening histories, or (B) respondents to self-sampling had moderate and severe under-screening histories. Model outcomes included quality-adjusted life-years (QALY) and lifetime costs. The “most cost-effective” strategy was identified as the strategy just below $100,000 per QALY gained.

Results: Mailing self-sampling device kits to all women noncompliant to screening within a 5- or 10-year period can be more effective and less costly than the current reminder letter policy; however, the optimal self-sampling strategy was dependent on the profile of self-sampling respondents. For example, “10-yearly self-sampling” is preferred ($95,500 per QALY gained) if “5-yearly self-sampling” could only attract moderate under-screeners; however, “5-yearly self-sampling” is preferred if this strategy could additionally attract severe under-screeners.

Conclusions: Targeted self-sampling of noncompliers likely represents good value-for-money; however, the preferred strategy is contingent on the screening histories and compliance of respondents.

Impact: The magnitude of the health benefit and optimal self-sampling strategy is dependent on the profile and behavior of respondents. Health authorities should understand these factors prior to selecting and implementing a self-sampling policy. Cancer Epidemiol Biomarkers Prev; 26(1); 95–103. ©2016 AACR.
Data from Overdiagnosis in Mammographic Screening because of Competing Risk of Death
Authors: Falk Ragnhild Sorum , Hofvind Solveig
Published: April 2023

Abstract
Background: Different definitions and estimates of overdiagnosis in mammographic screening reflect a substantial need to investigate and understand the complexity of the issue. This modeling study aims to estimate the number of overdiagnosed women, defined as those diagnosed with breast cancer who die from any cause within the lead-time period.

Methods: We used numbers from incidence and death statistics available online and published estimates of lead-time. Postulated cohorts of screened and not screened women ages 50 to 51 were followed for a period corresponding to 10 biennial screening exams during 20 years, and a further 10 years, to ages 78 to 79. The increase in breast cancer incidence because of screening was estimated based on lead-time. The proportion of women diagnosed with breast cancer who died within the lead-time period was assessed based on the differences in the cumulative number of breast cancer diagnosed in a nonscreened and screened cohort.

Results: The proportion of inevitable overdiagnosed women in a screened versus nonscreened cohort was 1.9% for England and Wales and 1.8% for Norway. Sensitivity analyses using various assumptions increased the estimates up to a maximum of 4%.

Conclusion: The proportion of women with breast cancer diagnosed after participation in a screening program who died within the estimated lead-time period was less than 4%. This inevitable proportion of overdiagnosis should be emphasized in the definition and communication of the issue.

Impact: The issue of overdiagnosis is complex and estimates should be interpreted with substantial care. Cancer Epidemiol Biomarkers Prev; 25(5); 759–65. ©2016 AACR.
Data from Associations of Coffee Drinking with Systemic Immune and Inflammatory Markers
Authors: Loftfield Erikka , Shiels Meredith S. , Graubard Barry I. , Katki Hormuzd A. , Chaturvedi Anil K. , Trabert Britton , Pinto Ligia A. , Kemp Troy J. , Shebl Fatma M. , Mayne Susan T. , Wentzensen Nicolas , Purdue Mark P. , Hildesheim Allan , Sinha Rashmi , Freedman Neal D.
Published: April 2023

Abstract
Background: Coffee drinking has been inversely associated with mortality as well as cancers of the endometrium, colon, skin, prostate, and liver. Improved insulin sensitivity and reduced inflammation are among the hypothesized mechanisms by which coffee drinking may affect cancer risk; however, associations between coffee drinking and systemic levels of immune and inflammatory markers have not been well characterized.

Methods: We used Luminex bead-based assays to measure serum levels of 77 immune and inflammatory markers in 1,728 older non-Hispanic Whites. Usual coffee intake was self-reported using a food frequency questionnaire. We used weighted multivariable logistic regression models to examine associations between coffee and dichotomized marker levels. We conducted statistical trend tests by modeling the median value of each coffee category and applied a 20% false discovery rate criterion to P values.

Results: Ten of the 77 markers were nominally associated (P trend < 0.05) with coffee drinking. Five markers withstood correction for multiple comparisons and included aspects of the host response namely chemotaxis of monocytes/macrophages (IFNγ, CX3CL1/fractalkine, CCL4/MIP-1β), proinflammatory cytokines (sTNFRII), and regulators of cell growth (FGF-2). Heavy coffee drinkers had lower circulating levels of IFNγ [odds ratios (OR), 0.35; 95% confidence intervals (CI), 0.16–0.75], CX3CL1/fractalkine (OR, 0.25; 95% CI, 0.10–0.64), CCL4/MIP-1β (OR, 0.48; 95% CI, 0.24–0.99), FGF-2 (OR, 0.62; 95% CI, 0.28–1.38), and sTNFRII (OR, 0.34; 95% CI, 0.15–0.79) than non-coffee drinkers.

Conclusions: Lower circulating levels of inflammatory markers among coffee drinkers may partially mediate previously observed associations of coffee with cancer and other chronic diseases.

Impact: Validation studies, ideally controlled feeding trials, are needed to confirm these associations. Cancer Epidemiol Biomarkers Prev; 24(7); 1052–60. ©2015 AACR.
Data from Tumor Intrinsic Subtype Is Reflected in Cancer-Adjacent Tissue
Authors: Casbas-Hernandez Patricia , Sun Xuezheng , Roman-Perez Erick , D'Arcy Monica , Sandhu Rupninder , Hishida Asahi , McNaughton Kirk K. , Yang Xiaohong R. , Makowski Liza , Sherman Mark E. , Figueroa Jonine D. , Troester Melissa A.
Published: April 2023

Abstract
Introduction: Overall survival of early-stage breast cancer patients is similar for those who undergo breast-conserving therapy (BCT) and mastectomy; however, 10% to 15% of women undergoing BCT suffer ipsilateral breast tumor recurrence. The risk of recurrence may vary with breast cancer subtype. Understanding the gene expression of the cancer-adjacent tissue and the stromal response to specific tumor subtypes is important for developing clinical strategies to reduce recurrence risk.

Methods: We utilized two independent datasets to study gene expression data in cancer-adjacent tissue from invasive breast cancer patients. Complementary in vitro cocultures were used to study cell–cell communication between fibroblasts and specific breast cancer subtypes.

Results: Our results suggest that intrinsic tumor subtypes are reflected in histologically normal cancer-adjacent tissue. Gene expression of cancer-adjacent tissues shows that triple-negative (Claudin-low or basal-like) tumors exhibit increased expression of genes involved in inflammation and immune response. Although such changes could reflect distinct immune populations present in the microenvironment, altered immune response gene expression was also observed in cocultures in the absence of immune cell infiltrates, emphasizing that these inflammatory mediators are secreted by breast-specific cells. In addition, although triple-negative breast cancers are associated with upregulated immune response genes, luminal breast cancers are more commonly associated with estrogen-response pathways in adjacent tissues.

Conclusions: Specific characteristics of breast cancers are reflected in the surrounding histologically normal tissue. This commonality between tumor and cancer-adjacent tissue may underlie second primaries and local recurrences.

Impact: Biomarkers derived from cancer-adjacent tissue may be helpful in defining personalized surgical strategies or in predicting recurrence risk. Cancer Epidemiol Biomarkers Prev; 24(2); 406–14. ©2014 AACR.
Data from Physical Activity in Relation to Risk of Hematologic Cancers: A Systematic Review and Meta-analysis
Authors: Jochem Carmen , Leitzmann Michael F. , Keimling Marlen , Schmid Daniela , Behrens Gundula
Published: April 2023

Abstract
Background: Despite the existence of numerous biologic pathways potentially linking increased physical activity to decreased risk of hematologic cancers, the associations between physical activity and subtype-specific hematologic cancers have not been comprehensively quantified.

Methods: We conducted a systematic review and meta-analysis of physical activity in relation to subtype-specific hematologic cancers. We summarized the data from 23 eligible studies (15 cohort and eight case–control studies) and estimated summary relative risks (RR) and 95% confidence intervals (CI) using random-effects models.

Results: When comparing high versus low physical activity levels, the RR for non-Hodgkin lymphoma was 0.91 (95% CI, 0.82–1.00), for Hodgkin lymphoma it was 0.86 (95% CI, 0.58–1.26), for leukemia it was 0.97 (95% CI, 0.84–1.13), and for multiple myeloma it was 0.86 (95% CI, 0.68–1.09). When focusing on subtypes of non-Hodgkin lymphoma, the RR for diffuse large B-cell lymphoma was 0.95 (95% CI, 0.80–1.14) and for follicular lymphoma it was 1.01 (95% CI, 0.83–1.22). In an exploratory analysis combining all hematologic cancers, high versus low physical activity levels yielded a statistically significant RR of 0.93 (95% CI, 0.88–0.99).

Conclusions: Physical activity showed statistically nonsignificant associations with risks of non-Hodgkin lymphoma, Hodgkin lymphoma, multiple myeloma, and leukemia. These findings may not represent a true lack of associations given the variation in high versus low physical activity definitions, the quality of physical activity assessments, and the variability in hematologic cancer classification schemes in individual studies.

Impact: Physical activity is unrelated to risks of subtype-specific hematologic cancers. Cancer Epidemiol Biomarkers Prev; 23(5); 833–46. ©2014 AACR.
Data from Serum Selenium, Genetic Variation in Selenoenzymes, and Risk of Colorectal Cancer: Primary Analysis from the Women's Health Initiative Observational Study and Meta-analysis
Authors: Takata Yumie , Kristal Alan R. , King Irena B. , Song Xiaoling , Diamond Alan M. , Foster Charles B. , Hutter Carolyn M. , Hsu Li , Duggan David J. , Langer Robert D. , Petrovitch Helen , Shikany James M. , Vaughan Thomas L. , Lampe Johanna W. , Prentice Ross L. , Peters Ulrike
Published: April 2023

Abstract
Background: Selenium may prevent colorectal cancer. However, several previous studies are small and few investigated the association between selenium and colorectal cancer among women whose selenium metabolism may differ from men. Furthermore, genetic variants in selenoenzymes may be associated with colorectal cancer risk.

Methods: This nested case–control study investigated whether serum selenium concentration and genetic variants in five selenoenzymes (glutathione peroxidase 1–4 and selenoprotein P) were associated with colorectal cancer risk in 804 colorectal cancer cases and 805 matched controls from the Women's Health Initiative (WHI) Observational Study. A meta-analysis was conducted to compare the WHI result with previous studies including 12 observational studies and two clinical trials on selenium.

Results: Within the WHI, selenium concentrations were relatively high (mean = 135.6 μg/L) and were not associated with colorectal cancer risk (Ptrend = 0.10); the adjusted OR comparing the fifth with first quintile was 1.26 (95% CI, 0.91–1.73). Moreover, genetic variants in selenoenzymes were not significantly associated with colorectal cancer risk. Consistent with the finding in WHI, our meta-analysis showed no association between selenium and colorectal tumor risk in women (OR = 0.97; 95% CI, 0.79–1.18) comparing the highest quantile with the lowest); however, in men, there was a significant inverse association (OR = 0.68; 95% CI, 0.57–0.82) (P = 0.01).

Conclusion: Consistent with previous studies, we observed no protective effect of selenium on colorectal cancer among women.

Impact: Our analyses suggest that a population with relatively high selenium concentrations, especially women, would not benefit from increasing selenium intake. Cancer Epidemiol Biomarkers Prev; 20(9); 1822–30. ©2011 AACR.
Data from Anal Cancer Incidence in the United States, 1977–2011: Distinct Patterns by Histology and Behavior
Authors: Shiels Meredith S. , Kreimer Aimée R. , Coghill Anna E. , Darragh Teresa M. , Devesa Susan S.
Published: April 2023

Abstract
Background: Although anal squamous cell carcinoma (SCC) and adenocarcinoma (ADC) are generally combined in cancer surveillance, their etiologies likely differ. Here, we describe demographic characteristics and trends in incidence rates (IR) of anal cancer by histology (SCC, ADC) and behavior (invasive, in situ) in the United States.

Methods: With data from the Surveillance, Epidemiology, and End Results (SEER) Program, we estimated age-adjusted anal cancer IRs across behavior/histology by demographic and tumor characteristics for 2000–2011. Trends in IRs and annual percent changes during 1977–2011 were also estimated and compared with rectal cancer.

Results: Women had higher rates of SCC [rate ratio (RR), 1.45; 95% confidence interval (CI), 1.40–1.50] and lower rates of ADC (RR, 0.68; 95% CI, 0.62–0.74) and squamous carcinoma in situ (CIS; RR, 0.36; 95% CI, 0.34–0.38) than men. Blacks had lower rates of SCC (RR, 0.82; 95% CI, 0.77–0.87) and CIS (RR, 0.90; 95% CI, 0.83–0.98) than non-Hispanic whites, but higher rates of ADC (RR, 1.48; 95% CI, 1.29–1.70). Anal cancer IRs were higher in men and blacks aged <40 years. During 1992–2011, SCC IRs increased 2.9%/year, ADC IRs declined nonsignificantly, and CIS IRs increased 14.2%/year. SCC and ADC IR patterns and trends were similar across anal and rectal cancers.

Conclusions: Rates of anal SCC and CIS have increased strongly over time, in contrast to rates of anal ADC, similar to trends observed for rectal SCC and ADC.

Impact: Anal SCC and ADC likely have different etiologies, but may have similar etiologies to rectal SCC and ADC, respectively. Strong increases in CIS IRs over time may reflect anal cancer screening patterns. Cancer Epidemiol Biomarkers Prev; 24(10); 1548–56. ©2015 AACR.
Data from The Interaction between Genetic Ancestry and Breast Cancer Risk Factors among Hispanic Women: The Breast Cancer Health Disparities Study
Authors: Hines Lisa M. , Sedjo Rebecca L. , Byers Tim , John Esther M. , Fejerman Laura , Stern Mariana C. , Baumgartner Kathy B. , Giuliano Anna R. , Torres-Mejia Gabriela , Wolff Roger K. , Harrall Kylie K. , Slattery Martha L.
Published: April 2023

Abstract
Background: Hispanic women have lower breast cancer incidence rates than non-Hispanic white (NHW) women. To what extent genetic versus nongenetic factors account for this difference is unknown.

Methods: Using logistic regression, we evaluated the interactive influences of established risk factors and ethnicity (self-identified and identified by ancestral informative markers) on breast cancer risk among 2,326 Hispanic and 1,854 NHW postmenopausal women from the United States and Mexico in the Breast Cancer Health Disparities Study.

Results: The inverse association between the percentage of Native American (NA) ancestry and breast cancer risk was only slightly attenuated after adjusting for known risk factors [lowest versus highest quartile: odds ratio (OR) =1.39, 95% confidence interval (CI) = 1.00–1.92 among U.S. Hispanics; OR = 1.92 (95% CI, 1.29–2.86) among Mexican women]. The prevalence of several risk factors, as well as the associations with certain factors and breast cancer risk, differed according to genetic admixture. For example, higher body mass index (BMI) was associated with reduced risk among women with lower NA ancestry only [BMI <25 versus >30: OR = 0.65 (95% CI, 0.44–0.98) among U.S. Hispanics; OR = 0.53 (95% CI, 0.29–0.97) among Mexicans]. The average number of risk factors among cases was inversely related to the percentage of NA ancestry.

Conclusions: The lower NA ancestry groups were more likely to have the established risk factors, with the exception of BMI. Although the majority of factors were associated with risk in the expected directions among all women, BMI had an inverse association among Hispanics with lower NA ancestry.

Impact: These data suggest that the established risk factors are less relevant for breast cancer development among women with more NA ancestry. Cancer Epidemiol Biomarkers Prev; 26(5); 692–701. ©2016 AACR.
Data from Improved Performance of Serum Alpha-Fetoprotein for Hepatocellular Carcinoma Diagnosis in HCV Cirrhosis with Normal Alanine Transaminase
Authors: Yang Ju Dong , Dai Jianliang , Singal Amit G. , Gopal Purva , Addissie Benyam D. , Nguyen Mindie H. , Befeler Alex S. , Reddy K. Rajender , Schwartz Myron , Harnois Denise M. , Yamada Hiroyuki , Gores Gregory J. , Feng Ziding , Marrero Jorge A. , Roberts Lewis R.
Published: April 2023

Abstract
Background: The utility of alpha-fetoprotein (AFP) for hepatocellular carcinoma (HCC) surveillance is controversial. We aimed to identify factors associated with elevated AFP and define the patients for whom AFP is effective for surveillance.

Methods: Data from the NCI Early Detection Research Network phase II HCC biomarker study (233 early-stage HCC and 412 cirrhotic patients) were analyzed. We analyzed 110 early-stage HCC and 362 cirrhotic hepatitis C virus (HCV) patients for external validation. Sensitivity, specificity, and area under the ROC curve (AUC) for HCC were calculated.

Results: HCV etiology, non-White race, and serum alanine transaminase (ALT) predicted elevated AFP in cirrhotics. Non-White race and ALT predicted elevated AFP in HCC patients. Higher AUC of AFP for HCC was noted in patients with HBV (0.85) and alcohol (0.84), whereas it was lower in patients with hepatitis C virus (HCV; 0.80) and nonviral/alcohol etiology (0.76). The AUC was higher in HCV patients with serum ALT ≤40 U/L than patients with serum ALT >40 U/L (0.91 vs. 0.75, P < 0.01). At 90% specificity, the sensitivity of AFP increased from 44% to 74% in Whites with HCV and from 50% to 85% in non-Whites with HCV. There was a trend toward higher AUC in HCV patients with serum ALT ≤40 U/L than those with serum ALT >40 U/L (0.79 vs. 0.69, P = 0.10) in the validation cohort.

Conclusions: The satisfactory performance of AFP in HCV patients with normal ALT should be further validated.

Impact: The AFP may serve as a valuable surveillance test in HCV patients with normal ALT. Cancer Epidemiol Biomarkers Prev; 26(7); 1085–92. ©2017 AACR.