bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from Racial Differences in the Association Between Preoperative Serum Cholesterol and Prostate Cancer Recurrence: Results from the SEARCH Database
Authors: Allott Emma H. , Howard Lauren E. , Aronson William J. , Terris Martha K. , Kane Christopher J. , Amling Christopher L. , Cooperberg Matthew R. , Freedland Stephen J.
Published: April 2023

Abstract
Background: Black men are disproportionately affected by both cardiovascular disease and prostate cancer. Epidemiologic evidence linking dyslipidemia, an established cardiovascular risk factor, and prostate cancer progression is mixed. As existing studies were conducted in predominantly non-black populations, research on black men is lacking.

Methods: We identified 628 black and 1,020 non-black men who underwent radical prostatectomy and never used statins before surgery in the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Median follow-up was 2.9 years. The impact of preoperative hypercholesterolemia on risk of biochemical recurrence was examined using multivariable, race-stratified proportional hazards. In secondary analysis, we examined associations with low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides, overall and among men with dyslipidemia.

Results: High cholesterol was associated with increased risk of recurrence in black [HRper10 mg/dL 1.06; 95% confidence interval (CI), 1.02–1.11] but not non-black men (HRper10 mg/dL 0.99; 95% CI, 0.95–1.03; Pinteraction = 0.011). Elevated triglycerides were associated with increased risk in both black and non-black men (HRper10 mg/dL 1.02; 95% CI, 1.00–1.03 and 1.02; 95% CI, 1.00–1.02, respectively; Pinteraction = 0.458). There were no significant associations between LDL or HDL and recurrence risk in either race. Associations with cholesterol, LDL, and triglycerides were similar among men with dyslipidemia, but low HDL was associated with increased risk of recurrence in black, but not non-black men with dyslipidemia (Pinteraction = 0.047).

Conclusion: Elevated cholesterol was a risk factor for recurrence in black but not non-black men, whereas high triglycerides were associated with increased risk regardless of race.

Impact: Significantly contrasting associations by race may provide insight into prostate cancer racial disparities. Cancer Epidemiol Biomarkers Prev; 25(3); 547–54. ©2016 AACR.
Data from Composite Three-Marker Assay for Early Detection of Kidney Cancer
Authors: Su Kim Dong , Choi Young Deuk , Moon Mihyang , Kang Suki , Lim Jong-Baeck , Kim Kyung Min , Park Kyung Mok , Cho Nam Hoon
Published: April 2023

Abstract
Background: Early detection of renal cell carcinoma using serum/plasma biomarkers remains challenging. To validate clinical performance of potential candidate markers for kidney tumors, three-marker assay composed of nicotinamide N-methyltransferase (NNMT), L-plastin (LCP1), and nonmetastatic cells 1 protein (NM23A) was evaluated.

Methods: Patients with kidney cancer and control group were included in the clinical evaluation. Participants were divided into cohorts representing the training group of control group including healthy and benign tumors (n = 102) and patients with kidney cancer (n = 87) that were used to identify criteria for scoring. Then, we developed a three-marker assay that was validated with a cohort of test group samples (n = 100). A scoring method based on the cut-point of each of the three markers was used to evaluate the diagnostic performance of the marker combination.

Results: Plasma levels of NNMT, LCP1, and NM23A were highly elevated in patients with kidney cancer (P < 0.0001). In 289 blind sample tests with control subjects (n = 175) and patients with kidney cancer (n = 114), the diagnostic accuracy of NNMT alone and the three-marker assay was 0.913 and 0.932, respectively. When 90% specificity was defined, the sensitivity of NNMT and the three-marker assay was 71.9% and 95.7%, respectively. The predictive value of the three-marker assay was 87.2% (+PPV) and 97% (−PPV).

Conclusions: The composite assay with NNMT, LCP1, and NM23A was a promising novel serum marker assay for the early detection of malignant kidney tumors covering subtypes of RCC with high diagnostic characteristics.

Impact: NNMT/LCP1/NM23A triple markers could be a helpful screening assay to detect early RCC. Cancer Epidemiol Biomarkers Prev; 22(3); 390–8. ©2013 AACR.
Data from Seroprevalence of Human Papillomavirus (HPV) Type 6 and 16 Vary by Anatomic Site of HPV Infection in Men
Authors: Lu Beibei , Viscidi Raphael P. , Wu Yougui , Nyitray Alan G. , Villa Luisa L. , Lazcano-Ponce Eduardo , Carvalho da Silva Roberto J. , Baggio Maria Luiza , Quiterio Manuel , Salmerón Jorge , Smith Danelle C. , Abrahamsen Martha , Papenfuss Mary , Giuliano Anna R.
Published: April 2023

Abstract
Background: It is largely unknown if antihuman papillomavirus (HPV) serum antibody responses vary by anatomic site of infection in men.

Methods: This study assessed type-specific anti-HPV serum antibody prevalence associated with corresponding HPV DNA detection in the external genitalia and the anal canal of 1,587 heterosexual men and 199 men who have sex with men (MSM).

Results: We observed that HPV 6 and 16 seroprevalence was higher in the presence of same HPV-type infection in the anal canal compared with same HPV-type infection in the external genitalia only, and among MSM compared with the heterosexual men. Seropositivity to HPV 6 was strongly associated with HPV 6 DNA detection in the anal canal but not in the external genitalia alone among both heterosexual men [adjusted prevalence ratio (APR), anal+/genital+ vs. anal−/genital−: 4.2, 95% confidence interval (CI), 11.7–10.5; anal+/genital− vs. anal−/genital−: 7.9 (95% CI, 3.7–17.0)] and MSM [APR, anal+/genital+ vs. anal−/genital−: 5.6 (95% CI, 2.7–11.9); anal+/genital− vs. anal−/genital−: 3.2 (95% CI, 2.1–4.9)]. Similar associations between seropositivity to HPV 16 and anal HPV 16 DNA detection were only observed in MSM [anal+/genital+ vs. anal−/genital−: 3.1 (95% CI, 2.0–5.0); anal+/genital− vs. anal−/genital−: 2.2 (95% CI, 1.3–3.5)].

Conclusion: Our data showed that seroprevalence varied by anatomic site of HPV infection, suggesting differences in epithelium type present at these anatomic sites may be relevant.

Impact: Our finding is instrumental in advancing our understanding of immune mechanism involved in anatomic site–specific antibody response. Cancer Epidemiol Biomarkers Prev; 21(9); 1542–6. ©2012 AACR.
Data from Cancer Risk and Subsequent Survival after Hospitalization for Intermittent Claudication
Authors: Onega Tracy , Baron John A. , Johnsen Søren P. , Pedersen Lars , Farkas Dóra K. , Sørensen Henrik T.
Published: April 2023

Abstract
Background: Intermittent claudication, muscle ischemia due to reduced arterial circulation, may be associated with an increased risk of cancer risk and death due to neoplasm-induced hypercoagulability and angiogenesis, or to shared risk factors, but the relation is not well understood.

Methods: We conducted a population-based cohort study using the Danish National Registry of Patients to identify patients with intermittent claudication from 1980 to 2011 and no history of cancer. We followed these patients for incident cancers using the Danish Cancer Registry and compared cancer incidence among patients with intermittent claudication to that expected in the general population. We also compared the survival of patients with cancer with and without claudication, matched for sex, cancer site, stage, age at diagnosis, and diagnosis year.

Results: A total of 53,762 patients with intermittent claudication were identified. We observed 6,270 incident cancers over a total 269,430 years of follow-up (mean, 5.0), compared with 4,306 cancer cases expected [standardized incidence ratio = 1.46; 95% confidence interval (CI), 1.42–1.49]. Cancer risk also increased after the exclusion of patients with a prior diagnosis of cerebrovascular disease, myocardial infarction, or diabetes, particularly for tobacco-related cancers. The elevated cancer risk persisted over 10 years of follow-up. For patients with cancer, diagnosis of intermittent claudication within 3 months preceding the cancer diagnosis did not influence survival, but before 3 months, was associated with modestly worse survival (mortality rate ratio = 1.19; 95% CI, 1.14–1.25).

Conclusions: Intermittent claudication is associated with an increased risk of cancer and poorer subsequent survival.

Impact: Clinical attention following intermittent claudication diagnosis may reveal incident cancers. Cancer Epidemiol Biomarkers Prev; 24(4); 744–8. ©2015 AACR.
Data from Predictors of the Occurrence of Smoking Discontinuation in Novice Adolescent Smokers
Authors: O'Loughlin Jennifer L. , Sylvestre Marie-Pierre , Dugas Erika N. , Karp Igor
Published: April 2023

Abstract
Background: While long-term cessation is an outcome of interest in adult smokers, little is known about discontinuing smoking in adolescent smokers. The objective was to identify the predictors of the occurrence of smoking discontinuation in novice smokers.

Methods: Data were available for 620 adolescent smokers participating in a longitudinal study on the natural course of nicotine dependence. Data on smoking discontinuation (i.e., stopping smoking for ≥12 consecutive months) were collected in 20 cycles over five years from grade 7 to 11 (1999–2005). Data on 37 potential predictors representing a wide range of demographic, psychosocial, health, lifestyle, smoking-related, and context-related characteristics were collected once, 2 to 3 times, or 20 times. Pooled logistic regression was used to test the association between each potential predictor and smoking discontinuation, adjusting for potential confounders.

Results: Forty percent of 620 participants discontinued smoking during follow up. Male sex [OR (95% confidence interval), 1.8 (1.3–2.4)], age [1.3 (1.1–1.5)], cigarette package warnings [0.6 (0.5–0.9)], team sports participation [1.4 (1.1–1.9)], family stress [0.7 (0.6–1.0)], worrying about weight [0.6 (0.5–0.9)], overweight [0.7 (0.5–1.0)], illicit drugs use [0.5 (0.4–0.7)], tolerance [0.6 (0.4–1.0)], and other nicotine dependence symptoms [1.0 (0.9–1.0)] were statistically significantly associated with smoking discontinuation.

Conclusions: Both individual and context-level factors were associated with smoking discontinuation.

Impact: Programs and policy targeting novice adolescent smokers may be more effective if factors associated with long-term smoking discontinuation are taken into consideration. In particular, young smokers may need help with dependence symptoms, body weight issues, family functioning, and polysubstance use. Cigarette package warnings may be effective in helping adolescents discontinue smoking. Cancer Epidemiol Biomarkers Prev; 23(6); 1090–101. ©2014 AACR.
Data from Impact of Treatment Exposures on Cardiovascular Risk and Insulin Resistance in Childhood Cancer Survivors
Authors: Baker K. Scott , Chow Eric J. , Goodman Pamela J. , Leisenring Wendy M. , Dietz Andrew C. , Perkins Joanna L. , Chow Lisa , Sinaiko Alan , Moran Antoinette , Petryk Anna , Steinberger Julia
Published: April 2023

Abstract
Background: Childhood cancer survivors (CCS) are more insulin resistant and have higher levels of several cardiovascular risk factors even while still children. This study examines specific treatment exposures associated with cardiovascular risk factors and insulin resistance.

Methods: CCS of ages 9 to 18 years at study entry and in remission 5 years or more from diagnosis (n = 319) and 208 sibling controls were recruited into this cross-sectional study that included physiologic assessment of insulin resistance (hyperinsulinemic euglycemic clamp) and assessment of cardiovascular risk factors. Regression and recursive tree modeling were used to ascertain treatment combinations associated with insulin resistance and cardiovascular risk.

Results: Mean current age of CCS was 14.5 years and 54% were male (siblings 13.6 years, 54% male). Diagnoses included leukemia (35%), brain tumors (36%), solid tumors (33%), or lymphoma (6%). Among CCS, analysis of individual chemotherapy agents failed to find associations with cardiovascular risk factors or insulin resistance. Compared with siblings, insulin resistance was significantly higher in CCS who received platinum plus cranial radiotherapy (CRT, 92% brain tumors) and in those who received steroids but no platinum (majority leukemia). Insulin resistance did not differ between CCS who received surgery alone versus siblings. Within survivor comparisons failed to elucidate treatment combinations that increased insulin resistance compared with those who received surgery only.

Conclusions: Exposure to platinum, CRT, or steroids is associated with insulin resistance and cardiovascular risk factors and should be taken into consideration in the development of screening recommendations for cardiovascular risk.

Impact: Earlier identification of CCS who may benefit from targeted prevention efforts may reduce their future risk of cardiovascular disease. Cancer Epidemiol Biomarkers Prev; 22(11); 1954–63. ©2013 AACR.
Data from Internet Use and Cancer-Preventive Behaviors in Older Adults: Findings from a Longitudinal Cohort Study
Authors: Xavier Andre Junqueira , d'Orsi Eleonora , Wardle Jane , Demakakos Panayotes , Smith Samuel G. , von Wagner Christian
Published: April 2023

Abstract
Background: The Internet is a key provider of health information, but little is known about its associations with cancer-preventive behaviors. This study investigated the associations between Internet use and cancer-preventive behaviors among older adults.

Methods: Data were taken from Waves 1 to 5 (2002–2011) of the English Longitudinal Study of Aging, a cohort study of men and women 50 years or older in England, United Kingdom. Internet use was recorded at each wave. Breast and colorectal screening, fruit and vegetable consumption, physical activity, and smoking were recorded at Wave 5. Social, cognitive, and physical function variables recorded at Wave 1 were analyzed as predictors of Internet use and included as covariates in analyses linking Internet use to behavior.

Results: Of 5,943 respondents, 41.4% did not report any Internet use, 38.3% reported using it in one to three waves (“intermittent users”), and 20.3% used it in all waves (“consistent users”). Internet use was higher in younger, male, White, wealthier, more educated respondents, and those without physical limitations. Multivariable analysis showed that consistent users were more likely than “never users” to report CRC screening, weekly moderate/vigorous physical activity, and five or more daily servings of fruit and vegetables, and less likely to report smoking. There was no significant association between Internet use and breast screening.

Conclusions: Internet use showed a quantitative association with cancer-preventive behaviors even after controlling for various social, cognitive, and physical correlates of Internet use.

Impact: Promoting Internet use among older adults from all backgrounds could contribute to improving cancer outcomes and reducing inequalities. Cancer Epidemiol Biomarkers Prev; 22(11); 2066–74. ©2013 AACR.
Data from Batch Effects and Pathway Analysis: Two Potential Perils in Cancer Studies Involving DNA Methylation Array Analysis
Authors: Harper Kristin N. , Peters Brandilyn A. , Gamble Mary V.
Published: April 2023

Abstract
Background: DNA methylation microarrays have become an increasingly popular means of studying the role of epigenetics in cancer, although the methods used to analyze these arrays are still being developed and existing methods are not always widely disseminated among microarray users.

Methods: We investigated two problems likely to confront DNA methylation microarray users: (i) batch effects and (ii) the use of widely available pathway analysis software to analyze results. First, DNA taken from individuals exposed to low and high levels of drinking water arsenic were plated twice on Illumina's Infinium 450 K HumanMethylation Array, once in order of exposure and again following randomization. Second, we conducted simulations in which random CpG sites were drawn from the 450 K array and subjected to pathway analysis using Ingenuity's IPA software.

Results: The majority of differentially methylated CpG sites identified in Run One were due to batch effects; few sites were also identified in Run Two. In addition, the pathway analysis software reported many significant associations between our data, randomly drawn from the 450 K array, and various diseases and biological functions.

Conclusions: These analyses illustrate the pitfalls of not properly controlling for chip-specific batch effects as well as using pathway analysis software created for gene expression arrays to analyze DNA methylation array data.

Impact: We present evidence that (i) chip-specific effects can simulate plausible differential methylation results and (ii) popular pathway analysis software developed for expression arrays can yield spurious results when used in tandem with methylation microarrays. Cancer Epidemiol Biomarkers Prev; 22(6); 1052–60. ©2013 AACR.
Data from The Contribution of Mammography Screening to Breast Cancer Incidence Trends in the United States: An Updated Age–Period–Cohort Model
Authors: Gangnon Ronald E. , Sprague Brian L. , Stout Natasha K. , Alagoz Oguz , Weedon-Fekjær Harald , Holford Theodore R. , Trentham-Dietz Amy
Published: April 2023

Abstract
Background: The impact of screening mammography on breast cancer incidence is difficult to disentangle from cohort- and age-related effects on incidence.

Methods: We developed an age–period–cohort model of ductal carcinoma in situ (DCIS) and invasive breast cancer incidence in U.S. females using cancer registry data. Five functions were included in the model to estimate stage-specific effects for age, premenopausal birth cohorts, postmenopausal birth cohorts, period (for all years of diagnosis), and a mammography period effect limited to women ages ≥40 years after 1982. Incidence with and without the mammography period effect was calculated.

Results: More recent birth cohorts have elevated underlying risk compared with earlier cohorts for both pre- and postmenopausal women. Comparing models with and without the mammography period effect showed that overall breast cancer incidence would have been 23.1% lower in the absence of mammography in 2010 (95% confidence intervals, 18.8–27.4), including 14.7% (9.5–19.3) lower for invasive breast cancer and 54.5% (47.4–59.6) lower for DCIS. Incidence of distant-staged breast cancer in 2010 would have been 29.0% (13.1–48.1) greater in the absence of mammography screening.

Conclusions: Mammography contributes to markedly elevated rates of DCIS and early-stage invasive cancers, but also contributes to substantial reductions in the incidence of metastatic breast cancer.

Impact: Mammography is an important tool for reducing the burden of breast cancer, but future work is needed to identify risk factors accounting for increasing underlying incidence and to distinguish between indolent and potentially lethal early-stage breast cancers that are detected via mammography. Cancer Epidemiol Biomarkers Prev; 24(6); 905–12. ©2015 AACR.
Data from Development and Validation of the Biobanking Attitudes and Knowledge Survey (BANKS)
Authors: Wells Kristen J. , Arevalo Mariana , Meade Cathy D. , Gwede Clement K. , Quinn Gwendolyn P. , Luque John S. , San Miguel Gloria , Watson Dale , Phillips Rebecca , Reyes Carmen , Romo Margarita , West Jim , Jacobsen Paul B.
Published: April 2023

Abstract
Background: No validated multiscale instruments exist that measure community members' views on biobanking and biospecimen donation. This study describes the development and psychometric properties of the English-language BANKS (Biobanking Attitudes and Knowledge Survey).

Methods: The BANKS was created by item generation through review of scientific literature, focus groups with community members, and input from a community advisory board. Items were refined through cognitive interviews. Content validity was assessed through an expert panel review. Psychometric properties of the BANKS were assessed in a sample of 85 community members.

Results: The final BANKS includes three scales: attitudes, knowledge, and self-efficacy; as well as three single items, which evaluated receptivity and intention to donate a biospecimen for research. Cronbach α coefficients for two scales that use Likert response format indicated high internal consistency (attitudes: α, 0.88; self-efficacy: α, 0.95). Content validity indices were moderate, ranging from 0.69 to 0.89. Intention to donate blood and intention to donate urine were positively correlated with attitudes, knowledge, self-efficacy, and receptivity to learning more about biobanking (P values range from 0.029 to <0.001).

Conclusions: The final BANKS shows evidence of satisfactory reliability and validity, is easy to administer, and is a promising tool to inform biospecimen research. Additional studies should be conducted with larger samples considering biospecimen donation to further assess the reliability and validity of the instrument.

Impact: A valid and reliable instrument measuring community members' views about biobanking may help researchers evaluate relevant communication interventions to enhance understanding, intention, and actual biospecimen donation. A Spanish-language BANKS is under development.

See all articles in this CEBP Focus section, “Community Network Program Centers.”

Cancer Epidemiol Biomarkers Prev; 23(3); 374–82. ©2014 AACR.
Data from Statistical Methods for Estimating the Cumulative Risk of Screening Mammography Outcomes
Authors: Hubbard Rebecca A. , Ripping Theodora M. , Chubak Jessica , Broeders Mireille J.M. , Miglioretti Diana L.
Published: April 2023

Abstract
Background: This study illustrates alternative statistical methods for estimating cumulative risk of screening mammography outcomes in longitudinal studies.

Methods: Data from the US Breast Cancer Surveillance Consortium (BCSC) and the Nijmegen Breast Cancer Screening Program in the Netherlands were used to compare four statistical approaches to estimating cumulative risk. We estimated cumulative risk of false-positive recall and screen-detected cancer after 10 screening rounds using data from 242,835 women ages 40 to 74 years screened at the BCSC facilities in 1993–2012 and from 17,297 women ages 50 to 74 years screened in Nijmegen in 1990–2012.

Results: In the BCSC cohort, a censoring bias model estimated bounds of 53.8% to 59.3% for false-positive recall and 2.4% to 7.6% for screen-detected cancer, assuming 10% increased or decreased risk among women screened for one additional round. In the Nijmegen cohort, false-positive recall appeared to be associated with subsequent discontinuation of screening leading to overestimation of risk of a false-positive recall based on adjusted discrete-time survival models. Bounds estimated by the censoring bias model were 11.0% to 19.9% for false-positive recall and 4.2% to 9.7% for screen-detected cancer.

Conclusion: Choice of statistical methodology can substantially affect cumulative risk estimates. The censoring bias model is appropriate under a variety of censoring mechanisms and provides bounds for cumulative risk estimates under varying degrees of dependent censoring.

Impact: This article illustrates statistical methods for estimating cumulative risks of cancer screening outcomes, which will be increasingly important as screening test recommendations proliferate. Cancer Epidemiol Biomarkers Prev; 25(3); 513–20. ©2015 AACR.
Data from Contributions of HIV to Non-Hodgkin Lymphoma Mortality Trends in the United States
Authors: Howlader Nadia , Shiels Meredith S. , Mariotto Angela B. , Engels Eric A.
Published: April 2023

Abstract
Background: The human immunodeficiency virus (HIV) epidemic has strongly influenced non-Hodgkin lymphoma (NHL) incidence in the U.S. general population, but its effects on NHL mortality trends are unknown.

Methods: Using SEER cancer registry data, we assessed NHL mortality rates in the United States (2005–2012) and mapped NHL deaths to prior incident cases. Data included HIV status at NHL diagnosis. We describe the proportion of NHL deaths linked to an HIV-infected case, for 3 AIDS-defining subtypes [diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma, and central nervous system (CNS) lymphoma] and within demographic categories. We also present incidence-based mortality (IBM) rates showing the impact of HIV on mortality trends and describe survival after NHL diagnosis by calendar year.

Results: Of 11,071 NHL deaths, 517 (4.6%) were in HIV-infected persons. This proportion was higher in deaths mapped to DLBCL (7.3% with HIV), Burkitt lymphoma (33.3%), and CNS lymphoma (17.6%), and among deaths from these subtypes, for people aged 20–49 years (46.6%), males (15.2%), and blacks (39.3%). IBM rates declined steeply during 2005–2012 for HIV-infected NHL cases (−7.6% per year, P = 0.001). This trend reflects a steep decline in incident NHL among HIV-infected people after 1996, when highly active antiretroviral therapy was introduced. Five-year cancer-specific survival improved more markedly among HIV-infected cases (9%–54%) than HIV-uninfected cases (62%–76%) during 1990–2008.

Conclusions: The HIV epidemic has strongly contributed to NHL deaths, especially for AIDS-defining NHL subtypes and groups with high HIV prevalence.

Impact: Declining NHL mortality rates for HIV-infected cases reflect both declining incidence and improving survival. Cancer Epidemiol Biomarkers Prev; 25(9); 1289–96. ©2016 AACR.
Data from Sex-Specific Associations between One-Carbon Metabolism Indices and Posttranslational Histone Modifications in Arsenic-Exposed Bangladeshi Adults
Authors: Howe Caitlin G. , Liu Xinhua , Hall Megan N. , Ilievski Vesna , Caudill Marie A. , Malysheva Olga , Lomax-Luu Angela M. , Parvez Faruque , Siddique Abu B. , Shahriar Hasan , Uddin Mohammad N. , Islam Tariqul , Graziano Joseph H. , Costa Max , Gamble Mary V.
Published: April 2023

Abstract
Background: Posttranslational histone modifications (PTHMs) are altered by arsenic, an environmental carcinogen. PTHMs are also influenced by nutritional methyl donors involved in one-carbon metabolism (OCM), which may protect against epigenetic dysregulation.

Methods: We measured global levels of three PTHMs, which are dysregulated in cancers (H3K36me2, H3K36me3, H3K79me2), in peripheral blood mononuclear cells (PBMC) from 324 participants enrolled in the Folic Acid and Creatine Trial, a randomized trial in arsenic-exposed Bangladeshi adults. Sex-specific associations between several blood OCM indices (folate, vitamin B12, choline, betaine, homocysteine) and PTHMs were examined at baseline using regression models, adjusted for multiple tests by controlling for the false discovery rate (PFDR). We also evaluated the effects of folic acid supplementation (400 μg/d for 12 weeks), compared with placebo, on PTHMs.

Results: Associations between choline and H3K36me2 and between vitamin B12 and H3K79me2 differed significantly by sex (Pdiff < 0.01 and <0.05, respectively). Among men, plasma choline was positively associated with H3K36me2 (PFDR < 0.05), and among women, plasma vitamin B12 was positively associated with H3K79me2 (PFDR < 0.01). Folic acid supplementation did not alter any of the PTHMs examined (PFDR = 0.80).

Conclusions: OCM indices may influence PTHMs in a sex-dependent manner, and folic acid supplementation, at this dose and duration, does not alter PTHMs in PBMCs.

Impact: This is the first study to examine the influences of OCM indices on PTHMs in a population that may have increased susceptibility to cancer development due to widespread exposure to arsenic-contaminated drinking water and a high prevalence of hyperhomocysteinemia. Cancer Epidemiol Biomarkers Prev; 26(2); 261–9. ©2016 AACR.
Data from Excess Mortality among HIV-Infected Individuals with Cancer in the United States
Authors: Coghill Anna E. , Pfeiffer Ruth M. , Shiels Meredith S. , Engels Eric A.
Published: April 2023

Abstract
Background: Human immunodefieciency virus (HIV)-infected persons are living longer in the era of effective HIV treatment, resulting in an increasing cancer burden in this population. The combined effects of HIV and cancer on mortality are incompletely understood.

Methods: We examined whether individuals with both HIV and cancer have excess mortality using data from the HIV/AIDS Cancer Match Study and the National Center for Health Statistics (1996–2010). We compared age, sex, and race-stratified mortality between people with and without HIV or one of the following cancers: lung, breast, prostate, colorectum, anus, Hodgkin lymphoma, or non-Hodgkin lymphoma. We utilized additive Poisson regression models that included terms for HIV, cancer, and an interaction for their combined effect on mortality. We report the number of excess deaths per 1,000 person-years for models with a significant interaction (P < 0.05).

Results: For all cancers examined except prostate cancer, at least one demographic subgroup of HIV-infected cancer patients experienced significant excess mortality. Excess mortality was most pronounced at younger ages (30–49 years), with large excesses for males with lung cancer (white race: 573 per 1,000 person-years; non-white: 503) and non-Hodgkin lymphoma (white: 236; non-white: 261), and for females with Hodgkin lymphoma (white: 216; non-white: 136) and breast cancer (non-white: 107).

Conclusions: In the era of effective HIV treatment, overall mortality in patients with both HIV and cancer was significantly higher than expected on the basis of mortality rates for each disease separately.

Impact: These results suggest that HIV may contribute to cancer progression and highlight the importance of improved cancer prevention and care for the U.S. HIV population. Cancer Epidemiol Biomarkers Prev; 26(7); 1027–33. ©2017 AACR.
Data from Biochemical Estimation of Noncompliance with Smoking of Very Low Nicotine Content Cigarettes
Authors: Benowitz Neal L. , Nardone Natalie , Hatsukami Dorothy K. , Donny Eric C.
Published: April 2023

Abstract
Background: The reduction of the nicotine content of cigarettes to nonaddicting levels is a potential federal regulatory intervention to reduce the prevalence of cigarette smoking and related disease. Many clinical trials on the effects and safety of nicotine reduction are ongoing. An important methodologic concern is noncompliance with reduced nicotine content cigarettes in the context of freely available conventional cigarettes. We propose two approaches using biomarkers to estimate noncompliance in smokers of very low nicotine content (VLNC) cigarettes in a clinical trial.

Methods: Data from 50 subjects in a study of gradual nicotine reduction were analyzed. Using plasma cotinine concentrations measured at baseline and while smoking VLNC cigarettes, we compared within-subject ratios of plasma cotinine comparing usual brand to VLNC in relation to nicotine content of these cigarettes. In another approach, we used nicotine pharmacokinetic data to estimate absolute plasma cotinine/cigarettes per day (CPD) threshold values for compliance based on the nicotine content of VLNC.

Results: The two approaches showed concordance, indicating at least 60% noncompliance with smoking VLNC. In a sensitivity analysis assuming extreme compensation and extreme values for nicotine metabolic parameters, noncompliance was still at least 40%, much higher than self-reported noncompliance.

Conclusion: Biomarker analysis demonstrates a high degree of noncompliance with smoking VLNC cigarettes, indicating that smokers are supplementing these with conventional cigarettes.

Impact: We propose a practical approach to assessing compliance with smoking VLNC in clinical trials of nicotine reduction. Cancer Epidemiol Biomarkers Prev; 24(2); 331–5. ©2014 AACR.
Data from Breast Cancer Risk Associated with Estrogen Exposure and Truncating Mutation Location in BRCA1/2 Carriers
Authors: Lecarpentier Julie , Noguès Catherine , Mouret-Fourme Emmanuelle , Buecher Bruno , Gauthier-Villars Marion , Stoppa-Lyonnet Dominique , Bonadona Valérie , Fricker Jean-Pierre , Berthet Pascaline , Caron Olivier , Coupier Isabelle , Pujol Pascal , Faivre Laurence , Gesta Paul , Eisinger François , Mari Véronique , Gladieff Laurence , Lortholary Alain , Luporsi Elisabeth , Leroux Dominique , Venat-Bouvet Laurence , Maugard Christine M. , Colas Chrystelle , Tinat Julie , Lasset Christine , Andrieu Nadine
Published: April 2023

Abstract
Background: Mutations in BRCA1/2 confer a high risk of breast cancer, but literature values of this risk vary. A genotype–phenotype correlation has been found in both genes, and the effect of reproductive factors differs according to mutation location. Therefore, we hypothesize that such a variation may exist for other factors related to estrogen exposure.

Methods: We used a weighted Cox regression model to assess variation in breast cancer risk with these factors using location of mutation in homogeneous breast cancer risk region of BRCA1/2 in the GENEPSO study.

Results: We found that late age at menarche reduced breast cancer risk by 31% and that among BRCA1 carriers, a long or a short menstrual cycle increased risk (by 65% and 73%, respectively). Among premenopausal women, overweight was associated with a 45% decrease in risk whereas underweight was associated with an increased risk (HR, 2.40). A natural menopause, mainly after age 50, was associated with a high breast cancer risk (HR, 2.46), and a significant interaction between menopause status and the location of mutations was found leading up to 10% variation in absolute risk according to the age at menopause.

Conclusions: As observed in the general population, a late menarche, a long or a short menstrual cycle, over- or underweight, and being postmenopausal were associated with breast cancer risk in BRCA1/2 carriers. The association with the menopause was observed only when the mutation was located in the “high-risk” zones.

Impact: Taking into account modifier factors, location of mutation might be important for the clinical management of BRCA1/2 mutation carriers. Cancer Epidemiol Biomarkers Prev; 24(4); 698–707. ©2015 AACR.
Data from Circulating Cancer-Associated Macrophage-Like Cells Differentiate Malignant Breast Cancer and Benign Breast Conditions
Authors: Adams Daniel L. , Adams Diane K. , Alpaugh R. Katherine , Cristofanilli Massimo , Martin Stuart S. , Chumsri Saranya , Tang Cha-Mei , Marks Jeffrey R.
Published: April 2023

Abstract
Background: Blood-based testing can be used as a noninvasive method to recover and analyze circulating tumor-derived cells for clinical use. Circulating cancer-associated macrophage-like cells (CAML) are specialized myeloid cells found in peripheral blood and associated with the presence of solid malignancies. We measured CAMLs prospectively in peripheral blood to ascertain their prevalence, specificity, and sensitivity in relation to breast disease status at clinical presentation.

Methods: We report on two related but separate studies: 1) CellSieve microfilters were used to isolate CAMLs from blood samples of patients with known malignant disease (n = 41). Prevalence and specificity was compared against healthy volunteers (n = 16). 2) A follow-up double-blind pilot study was conducted on women (n = 41) undergoing core-needle biopsy to diagnose suspicious breast masses.

Results: CAMLs were found in 93% of known malignant patients (n = 38/41), averaging 19.4 cells per sample, but none in the healthy controls. In subjects undergoing core biopsy for initial diagnosis, CAMLs were found in 88% of subjects with invasive carcinoma (n = 15/17) and 26% with benign breast conditions (n = 5/19).

Conclusion: These preliminary pilot studies suggest that the presence of CAMLs may differentiate patients with malignant disease, benign breast conditions, and healthy individuals.

Impact: We supply evidence that this previously unidentified circulating stromal cell may have utility as a screening tool to detect breast cancer in various malignancies, irrespective of disease stage. Cancer Epidemiol Biomarkers Prev; 25(7); 1037–42. ©2016 AACR.
Data from Epstein–Barr Virus Serology as a Potential Screening Marker for Nasopharyngeal Carcinoma among High-Risk Individuals from Multiplex Families in Taiwan
Authors: Coghill Anna E. , Hsu Wan-Lun , Pfeiffer Ruth M. , Juwana Hedy , Yu Kelly J. , Lou Pei-Jen , Wang Cheng-Ping , Chen Jen-Yang , Chen Chien-Jen , Middeldorp Jaap M. , Hildesheim Allan
Published: April 2023

Abstract
Background: Nasopharyngeal carcinoma (NPC) is an Epstein–Barr virus (EBV)–associated cancer that is highly treatable when diagnosed early, with 5-year disease-free survival of approximately 90%. However, NPC is typically diagnosed at advanced stages, in which disease-free survival is <50%. There is, therefore, a need for clinical tools to assist in early NPC detection, particularly among high-risk individuals.

Methods: We evaluated the ability of anti-EBV IgA antibodies to detect incident NPC among high-risk Taiwanese individuals. NPC cases (N = 21) and age- and sex-matched controls (N = 84) were selected. Serum collected before NPC diagnosis was tested for ELISA-based IgA antibodies against the following EBV peptides: EBNA1, VCAp18, EAp138, Ead_p47, and VCAp18 + EBNA1 peptide mixture. The sensitivity, specificity, and screening program parameters were calculated.

Results: EBNA1 IgA had the best performance characteristics. At an optimized threshold value, EBNA1 IgA measured at baseline identified 80% of the high-risk individuals who developed NPC during follow-up (80% sensitivity). However, approximately 40% of high-risk individuals who did not develop NPC also tested positive (false positives). Application of EBNA1 IgA as a biomarker to detect incident NPC in a previously unscreened, high-risk population revealed that 164 individuals needed to be screened to detect 1 NPC and that 69 individuals tested positive per case detected.

Conclusions: EBNA1 IgA proved to be a sensitive biomarker for identifying incident NPC, but future work is warranted to develop more specific screening tools to decrease the number of false positives.

Impact: Results from this study could inform decisions about screening biomarkers and referral thresholds for future NPC early-detection program evaluations. Cancer Epidemiol Biomarkers Prev; 23(7); 1213–9. ©2014 AACR.
Data from The PALB2 Gene Is a Strong Candidate for Clinical Testing in BRCA1- and BRCA2-Negative Hereditary Breast Cancer
Authors: Janatova Marketa , Kleibl Zdenek , Stribrna Jana , Panczak Ales , Vesela Kamila , Zimovjanova Martina , Kleiblova Petra , Dundr Pavel , Soukupova Jana , Pohlreich Petr
Published: April 2023

Abstract
Background: Several reports indicate that inherited mutations in the PALB2 gene predispose to breast cancer. However, there is little agreement about the clinical relevance and usefulness of mutation screening in this gene. We analyzed the prevalence and spectrum of germline mutations in PALB2 to estimate their contribution to hereditary breast and/or ovarian cancer in the Czech Republic.

Methods: The entire PALB2 coding region was sequenced in 409 breast/ovarian cancer patients negative for BRCA1 and BRCA2 mutations. Testing for large genomic rearrangements (LGR) was performed by multiplex ligation-dependent probe amplification (MLPA) analysis.

Results: We have identified 13 different pathogenic alterations including 10 truncating mutations and three LGRs in 16 of 409 patients (3.9%), whereas one truncating mutation was found in a group of 1,226 controls (0.08%; P = 2.6 × 10−9). Three novel LGRs included deletions involving exons 7–8 and 9–10, respectively, and a duplication spanning exons 9–11. Five frameshift and two nonsense mutations were novel, whereas three truncating mutations were described previously. The only recurrent mutation was the c.172_175delTTGT detected in four unrelated breast cancer individuals.

Conclusions: Our analyses demonstrated the significant role of the PALB2 gene in breast cancer susceptibility. The highest frequency of PALB2 mutations (comparable with that previously reported for BRCA2) was found in a subgroup of patients with hereditary breast cancer (HBC) (13/235; 5.5%).

Impact: Our results show that mutation analysis of the PALB2 gene, including the analysis of LGRs, is primarily indicated in patients with HBC in case of their BRCA1 and BRCA2 negativity. Cancer Epidemiol Biomarkers Prev; 22(12); 2323–32. ©2013 AACR.
Data from Racial Differences in the Incidence and Clearance of Human Papilloma Virus (HPV): The HPV in Men (HIM) Study
Authors: Schabath Matthew B. , Villa Luisa L. , Lin Hui-Yi , Fulp William J. , Akogbe Gabriel O. , Abrahamsen Martha E. , Papenfuss Mary R. , Lazcano-Ponce Eduardo , Salmerón Jorge , Quiterio Manuel , Giuliano Anna R.
Published: April 2023

Abstract
Background: This analysis assessed the acquisition (incidence) and persistence (clearance) of human papilloma virus (HPV) infection by self-reported race among men in The HPV in Men (HIM) Study, a multinational prospective study of the natural history of genital HPV infections.

Methods: Self-reported race was categorized as White, Black, Asian/Pacific Islander (PI), or multiple and mixed race. Genital samples were combined for HPV DNA testing and categorized by any, oncogenic, and non-oncogenic HPV infections.

Results: Asian/PI race had significantly the lowest incidence of any, oncogenic, and non-oncogenic HPV infection (P < 0.001). In multivariable analyses, Asian/PI race was associated with a lower probability of acquiring any [HR = 0.63; 95% confidence interval (CI), 0.42–0.95] and non-oncogenic HPV infection (HR = 0.61; 95% CI, 0.40–0.93) when compared to Whites. No significant associations were evident for Asian/PI race for clearance. Multiple and mixed race was significantly associated with lower probability of acquiring non-oncogenic HPV infection (HR = 0.83; 95% CI, 0.69–0.99) and borderline significant associations were observed for any HPV (HR = 0.91) and oncogenic infections (HR = 0.92). Multiple and mixed race was associated with a lower probability of clearing any (HR = 0.92; 95% CI, 0.84–1.00) and oncogenic HPV infections (HR = 0.85; 95% CI, 0.75–0.95).

Conclusion: Asian/PI race had the lowest incidence of HPV and exhibited a lower probability of acquiring new HPV infections. Multiple and mixed race had the second lowest incidence of infection and was associated with a lower probability of acquiring and clearing an HPV infection.

Impact: Race-specific differences in HPV infection could be due to behavior, innate genetic differences, or circulating intratypic HPV variants. Cancer Epidemiol Biomarkers Prev; 22(10); 1762–70. ©2013 AACR.
Data from HPV Type Attribution in High-Grade Cervical Lesions: Assessing the Potential Benefits of Vaccines in a Population-Based Evaluation in the United States
Authors: Hariri Susan , Unger Elizabeth R. , Schafer Sean , Niccolai Linda M. , Park Ina U. , Bloch Karen C. , Bennett Nancy M. , Steinau Martin , Johnson Michelle L. , Markowitz Lauri E.
Published: April 2023

Abstract
Background: Two currently available vaccines targeting human papillomavirus (HPV) types 16 and 18 could prevent 70% of cervical cancers and 50% of high-grade cervical lesions. Next-generation vaccines against additional types, such as a candidate 9-valent vaccine against HPV6/11/16/18/31/33/45/52/58, could further reduce HPV-associated disease burden.

Methods: HPV was typed in archived tissues from women ages 21 to 39 years residing in five catchment areas in the United States with cervical intraepithelial neoplasia 2/3 and adenocarcinoma in situ (CIN2+) using L1 consensus PCR and type-specific hybridization. Type attribution was estimated using weights to account for lesions with multiple types detected.

Results: From 2008 to 2011, 5,498 of 6,306 (87.2%) specimens obtained from 8,469 women with CIN2+ had valid typing results; HPV DNA was detected in 97.3%. Overall, 50.1% of lesions were attributable to HPV16/18, ranging from 50.3% to 52.4% among those ages 21 to 34 years, and significantly declined in 35 to 39 year-olds (43.5%). HPV16/18 attribution was higher in non-Hispanic whites (56.4%) versus racial/ethnic minorities (range, 41.8%–45.9%; P < 0.001). HPV31/33/45/52/58 attribution was 25.0% overall and increased with age (P < 0.001). A higher proportion of CIN2+ was attributable to HPV31/33/45/52/58 in non-Hispanic black (29.9%), Hispanic (29.2%), and Asian (33.1%) women compared with non-Hispanic whites (22.8%; P < 0.001).

Conclusions: Overall, 75% of lesions were attributable to 7 oncogenic HPV types: 50% to HPV16/18 and 25% to HPV31/33/45/52/58. HPV16/18 had the largest attributable fraction in CIN2+ across all subpopulations, although to a lesser extent in older women and racial/ethnic minorities.

Impact: Vaccines targeting additional oncogenic HPV types could prevent more high-grade cervical lesions, especially among racial/ethnic minorities. Cancer Epidemiol Biomarkers Prev; 24(2); 393–9. ©2014 AACR.
Data from A Simulation Model to Predict the Impact of Prophylactic Surgery and Screening on the Life Expectancy of BRCA1 and BRCA2 Mutation Carriers
Authors: Sigal Bronislava M. , Munoz Diego F. , Kurian Allison W. , Plevritis Sylvia K.
Published: April 2023

Abstract
Background: Women with inherited mutations in the BRCA1 or BRCA2 (BRCA1/2) genes are recommended to undergo a number of intensive cancer risk-reducing strategies, including prophylactic mastectomy, prophylactic oophorectomy, and screening. We estimate the impact of different risk-reducing options at various ages on life expectancy.

Methods: We apply our previously developed Monte Carlo simulation model of screening and prophylactic surgery in BRCA1/2 mutation carriers. Here, we present the mathematical formulation to compute age-specific breast cancer incidence in the absence of prophylactic oophorectomy, which is an input to the simulation model, and provide sensitivity analysis on related model parameters.

Results: The greatest gains in life expectancy result from conducting prophylactic mastectomy and prophylactic oophorectomy immediately after BRCA1/2 mutation testing; these gains vary with age at testing, from 6.8 to 10.3 years for BRCA1 and 3.4 to 4.4 years for BRCA2 mutation carriers. Life expectancy gains from delaying prophylactic surgery by 5 to 10 years range from 1 to 9.9 years for BRCA1 and 0.5 to 4.2 years for BRCA2 mutation carriers. Adding annual breast screening provides gains of 2.0 to 9.9 years for BRCA1 and 1.5 to 4.3 years for BRCA2. Results were most sensitive to variations in our assumptions about the magnitude and duration of breast cancer risk reduction due to prophylactic oophorectomy.

Conclusions: Life expectancy gains depend on the type of BRCA mutation and age at interventions. Sensitivity analysis identifies the degree of breast cancer risk reduction due to prophylactic oophorectomy as a key determinant of life expectancy gain.

Impact: Further study of the impact of prophylactic oophorectomy on breast cancer risk in BRCA1/2 mutation carriers is warranted. Cancer Epidemiol Biomarkers Prev; 21(7); 1066–77. ©2012 AACR.