bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from Reallocating Time to Sleep, Sedentary Time, or Physical Activity: Associations with Waist Circumference and Body Mass Index in Breast Cancer Survivors
Authors: Boyle Terry , Vallance Jeff K. , Buman Matthew P. , Lynch Brigid M.
Published: April 2023

Abstract
Background: Moderate-to-vigorous intensity physical activity (MVPA) is inversely associated with waist circumference and body mass index (BMI) among breast cancer survivors. Limited research has focused on behaviors that account for larger portions of the day [sleep, sedentary time, and light-intensity physical activity (LPA)]. We investigated the interdependent associations of self-reported sleep, objectively assessed prolonged and short bouts of sedentary time, total LPA, and total MVPA with waist circumference and BMI.

Methods: A cross-sectional sample of breast cancer survivors (N = 256, mean age = 60 years; mean time since diagnosis = 3 years) wore an Actigraph GT3X+ accelerometer during waking hours for 7 days. Participants completed the Pittsburgh Sleep Quality Index and self-reported their waist circumference, height, and weight. An isotemporal substitution approach was used in linear regression models to explore the associations of reallocating time to sleep, sedentary and active behaviors on waist circumference, and BMI, after adjusting for potential confounders.

Results: Reallocating 30 minutes to MVPA was significantly associated with lower waist circumference when allocated from sleep (−2.50 cm), prolonged sedentary time (−2.51 cm), or LPA (−2.71 cm). Reallocating 30 minutes of prolonged sedentary time to nonprolonged sedentary time was significantly associated with lower waist circumference (−0.94 cm). Similar results were observed for BMI.

Conclusions: Reallocating 30 minutes to MVPA was associated with significantly lower waist circumference and BMI, as was reallocating 30 minutes of prolonged sedentary time to 30 minutes of nonprolonged sedentary time.

Impact: Increasing MVPA levels and decreasing time spent in prolonged, unbroken sedentary bouts may be avenues for improving body composition in this population. Cancer Epidemiol Biomarkers Prev; 26(2); 254–60. ©2016 AACR.
Data from HIV Infection and Survival of Lymphoma Patients in the Era of Highly Active Antiretroviral Therapy
Authors: Han Xuesong , Jemal Ahmedin , Hulland Erin , Simard Edgar P. , Nastoupil Loretta , Ward Elizabeth , Flowers Christopher R.
Published: April 2023

Abstract
Background: Highly active antiretroviral therapy (HAART) has extended the life expectancy of patients with HIV/AIDS to approach that of the general population. However, it remains unclear whether HIV infection affects the survival of patients with lymphoma in the HAART era.

Methods: Patients diagnosed with Hodgkin lymphoma, diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma, peripheral T-cell lymphoma (PTCL), or follicular lymphoma during 2004–2011 were identified from the National Cancer Database. Survival analyses were conducted, where each HIV-infected patient was propensity score matched to a HIV-uninfected patient on the basis of demographic factors, clinical features, and treatment characteristics.

Results: Among 179,520 patients, the prevalence of HIV-infection ranged from 1.0% for follicular lymphoma, 3.3% for PTCL, 4.7% for Hodgkin lymphoma, 5.4% for DLBCL, to 29% for Burkitt lymphoma. HIV infection was significantly associated with inferior overall survival for patients with each lymphoma subtype: Hodgkin lymphoma [HR, 1.47; 95% confidence interval (CI), 1.25–1.74], DLBCL (HR, 1.95; 95% CI, 1.80–2.11), Burkitt lymphoma (HR, 1.46; 95% CI, 1.24–1.73), PTCL (HR, 1.43; 95% CI, 1.14–1.79), and follicular lymphoma (HR, 1.44; 95% CI, 1.04–2.00).

Conclusions: HIV/AIDS continues to be independently associated with increased risk of death among patients with lymphoma in the HAART era in the United States, and the association varies by lymphoma histologic subtype.

Impact: Examination of effective management strategies for patients with HIV/AIDS-associated lymphoma and enrollment of patients in prospective clinical trials are needed to improve patient outcomes. Cancer Epidemiol Biomarkers Prev; 26(3); 303–11. ©2016 AACR.
Data from Postmenopausal Hormone Therapy and Breast Cancer Prognostic Characteristics: A Linkage between Nationwide Registries
Authors: Román Marta , Graff-Iversen Sidsel , Weiderpass Elisabete , Vangen Siri , Sakshaug Solveig , Hofvind Solveig , Ursin Giske
Published: April 2023

Abstract
Background: The effects of use of different types of hormone therapy on breast cancer risk according to prognostic factors are largely unknown.

Methods: We linked data from the Norwegian Prescription Database and the Cancer Registry of Norway during 2004 to 2009 on all women ages 45 to 79 years (N = 686,614). We estimated rate ratios and 95% confidence intervals for breast cancer in relation to hormone therapy using Poisson regression.

Results: During an average 4.8 years of follow-up, 7,910 invasive breast cancers were diagnosed. Compared with nonusers of hormone therapy, users of estradiol and tibolone were more likely to be diagnosed with grade I, lymph node–negative, and estrogen receptor–positive (ER+)/progesterone receptor–positive (PR+) tumors. However, compared with nonusers, users of the most common estrogen and progestin combinations [estradiol–norethisterone acetate (NETA) preparations (Kliogest, Activelle or Trisekvens)] were at a 4- to 5-fold elevated risk of grade I tumors, 3-fold elevated risk of lymph node–negative tumors, and 3- to 4-fold elevated risk of ER+/PR+ tumors. Importantly, estradiol–NETA users were also at a 2- to 3-fold increased risk of medium differentiated (grade II) tumors and tumors with lymph node involvement.

Conclusions: Use of oral estradiol, tibolone, and estradiol–NETA predominantly increases the risk of breast cancer with favorable prognosis characteristics. However, use of estradiol–NETA preparations also increases the risk of breast cancers with less favorable characteristics.

Impact: The hormone therapy preparations most commonly used in the Nordic countries are associated with both breast cancers with good and less favorable prognosis characteristics. Cancer Epidemiol Biomarkers Prev; 25(11); 1464–73. ©2016 AACR.
Data from Indoor Tanning Dependence in Young Adult Women
Authors: Mays Darren , Atkins Michael B. , Ahn Jaeil , Tercyak Kenneth P.
Published: April 2023

Abstract
Background: There is mounting evidence that young people can develop a dependence on indoor tanning, but research on factors associated with indoor tanning dependence remains limited.

Methods: This cross-sectional study investigated factors associated with indoor tanning dependence in a community sample of 389 non-Hispanic white young adult women ages 18 to 30 who had indoor tanned ≥1 time in the past year. Participants completed measures of indoor tanning dependence, including the modified CAGE and modified Diagnostic and Statistical Manual for Mental Disorders-IV psychiatric screening assessments, indoor tanning behavior and beliefs, and behavioral and psychiatric comorbidity.

Results: Overall, 22.6% of the sample screened positive for indoor tanning dependence. In multivariable analyses, indoor tanning dependence was associated with younger age of indoor tanning initiation [adjusted odds ratio (aOR) = 0.79; P = 0.017], indoor tanning ≥20 times in the past year (aOR = 3.03; P = 0.015), stronger beliefs about the benefits of tanning (aOR = 2.15; P = 0.004), greater perceived susceptibility to indoor tanning risks (aOR = 2.72; P < 0.001), stronger beliefs about physical appearance (aOR = 1.73; P = 0.037), and depressive symptoms (aOR = 3.79; P < 0.001).

Conclusions: Indoor tanning dependence among young, non-Hispanic white women is associated with behaviors that increase the risk of skin cancer, beliefs favoring the perceived benefits of tanning, and comorbid risks such as stronger beliefs about physical appearance and depressed mood.

Impact: Comprehensive skin cancer prevention efforts should address indoor tanning dependence among young women and its leading risk factors. Cancer Epidemiol Biomarkers Prev; 26(11); 1636–43. ©2017 AACR.
Data from Statin Use and Prostate Cancer Aggressiveness: Results from the Population-Based North Carolina–Louisiana Prostate Cancer Project
Authors: Allott Emma H. , Farnan Laura , Steck Susan E. , Arab Lenore , Su L. Joseph , Mishel Merle , Fontham Elizabeth T.H. , Mohler James L. , Bensen Jeannette T.
Published: April 2023

Abstract
Background: Although statin use has been associated with reduced prostate cancer aggressiveness, the impact of race and patient characteristics on this association is not well understood. We examined the association between statin use and prostate cancer aggressiveness in Caucasians (CA) and African Americans (AA) and explored effect modification by health-seeking behaviors associated with statin use.

Methods: Of 1,930 cases from The North Carolina-Louisiana Prostate Cancer Project, 344 (18%) were classified as aggressive based on clinical criteria. Utilizing nonaggressive cases as referent, logistic regression was used to examine the association between statin use and prostate cancer aggressiveness, overall and stratified by race. Smoking and prostate cancer screening were examined as effect modifiers of this association.

Results: There was an inverse association between statin use and prostate cancer aggressiveness [OR, 0.74; 95% confidence interval (CI), 0.56–0.96], with comparable effect estimates in both races. Although not statistically significant, statin use was associated with reduced ORs for aggressive prostate cancer in never-screened men (OR, 0.79; 95% CI, 0.45–1.39), men screened at low/recommended frequency (≤once/year; OR, 0.66; 95% CI, 0.41–1.06), and men screened at high frequency (>once/year; OR, 0.78; 95% CI, 0.53–1.15). Inverse associations between statins and aggressive prostate cancer were strongest in never smokers (OR, 0.42; 95% CI, 0.25–0.72), attenuated in former smokers (OR, 0.84; 95% CI, 0.59–1.19), and absent in current smokers (OR, 1.36; 95% CI, 0.70–2.64).

Conclusions: Statin use was associated with reduced prostate cancer aggressiveness in CA and AAs, with strongest inverse associations in nonsmokers.

Impact: Health-seeking behaviors associated with statin use should be considered when examining the impact of statins on prostate cancer aggressiveness. Cancer Epidemiol Biomarkers Prev; 25(4); 670–7. ©2016 AACR.
Data from Adolescents and Young Adults with Acute Lymphoblastic Leukemia and Acute Myeloid Leukemia: Impact of Care at Specialized Cancer Centers on Survival Outcome
Authors: Wolfson Julie , Sun Can-Lan , Wyatt Laura , Stock Wendy , Bhatia Smita
Published: April 2023

Abstract
Background: Adolescents and young adults (AYA; 15–39 years) with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) experience inferior survival when compared with children. Impact of care at NCI-designated Comprehensive Cancer Centers (CCC) or Children's Oncology Group sites (COG) on survival disparities remains unstudied.

Methods: Using the Los Angeles cancer registry, we identified 1,870 ALL or AML patients between 1 and 39 years at diagnosis. Cox regression analyses assessed risk of mortality; younger age + CCC/COG served as the referent group. Logistic regression was used to determine odds of care at CCC/COG, adjusting for variables above.

Results: ALL outcome: AYAs at non-CCC/COG experienced inferior survival (15–21 years: HR = 1.9, P = 0.005; 22–29 years: HR = 2.6, P < 0.001; 30–39 years: HR = 3.0, P < 0.001). Outcome at CCC/COG was comparable between children and young AYAs (15–21 years: HR = 1.3, P = 0.3; 22–29 years: HR = 1.2, P = 0.2) but was inferior for 30- to 39-year-olds (HR = 3.4, P < 0.001). AML outcome: AYAs at non-CCC/COG experienced inferior outcome (15–21 years: HR = 1.8, P = 0.02; 22–39 years: HR = 1.4, P = 0.06). Outcome at CCC/COG was comparable between children and 15- to 21-year-olds (HR = 1.3, P = 0.4) but was inferior for 22- to 39-year-olds (HR = 1.7, P = 0.05). Access: 15- to 21-year-olds were less likely to use CCC/COG than children (P < 0.001). In 22- to 39-year-olds, public/uninsured (ALL: P = 0.004; AML<0.001), African American/Hispanics (ALL: P = 0.03), and 30- to 39-year-olds (ALL: P = 0.03) were less likely to use CCC/COG.

Conclusions: Poor survival in AYAs with ALL and AML is mitigated by care at CCC/COG. Barriers to CCC/COG care include public/uninsured, and African American/Hispanic race/ethnicity.

Impact: Care at CCC/COG explains, in part, inferior outcomes in AYAs with ALL and AML. Key sociodemographic factors serve as barriers to care at specialized centers. Cancer Epidemiol Biomarkers Prev; 26(3); 312–20. ©2017 AACR.
Data from Quantifying the Genetic Correlation between Multiple Cancer Types
Authors: Lindström Sara , Finucane Hilary , Bulik-Sullivan Brendan , Schumacher Fredrick R. , Amos Christopher I. , Hung Rayjean J. , Rand Kristin , Gruber Stephen B. , Conti David , Permuth Jennifer B. , Lin Hui-Yi , Goode Ellen L. , Sellers Thomas A. , Amundadottir Laufey T. , Stolzenberg-Solomon Rachael , Klein Alison , Petersen Gloria , Risch Harvey , Wolpin Brian , Hsu Li , Huyghe Jeroen R. , Chang-Claude Jenny , Chan Andrew , Berndt Sonja , Eeles Rosalind , Easton Douglas , Haiman Christopher A. , Hunter David J. , Neale Benjamin , Price Alkes L. , Kraft Peter
Published: April 2023

Abstract
Background: Many cancers share specific genetic risk factors, including both rare high-penetrance mutations and common SNPs identified through genome-wide association studies (GWAS). However, little is known about the overall shared heritability across cancers. Quantifying the extent to which two distinct cancers share genetic origin will give insights to shared biological mechanisms underlying cancer and inform design for future genetic association studies.

Methods: In this study, we estimated the pair-wise genetic correlation between six cancer types (breast, colorectal, lung, ovarian, pancreatic, and prostate) using cancer-specific GWAS summary statistics data based on 66,958 case and 70,665 control subjects of European ancestry. We also estimated genetic correlations between cancers and 14 noncancer diseases and traits.

Results: After adjusting for 15 pair-wise genetic correlation tests between cancers, we found significant (P < 0.003) genetic correlations between pancreatic and colorectal cancer (rg = 0.55, P = 0.003), lung and colorectal cancer (rg = 0.31, P = 0.001). We also found suggestive genetic correlations between lung and breast cancer (rg = 0.27, P = 0.009), and colorectal and breast cancer (rg = 0.22, P = 0.01). In contrast, we found no evidence that prostate cancer shared an appreciable proportion of heritability with other cancers. After adjusting for 84 tests studying genetic correlations between cancer types and other traits (Bonferroni-corrected P value: 0.0006), only the genetic correlation between lung cancer and smoking remained significant (rg = 0.41, P = 1.03 × 10−6). We also observed nominally significant genetic correlations between body mass index and all cancers except ovarian cancer.

Conclusions: Our results highlight novel genetic correlations and lend support to previous observational studies that have observed links between cancers and risk factors.

Impact: This study demonstrates modest genetic correlations between cancers; in particular, breast, colorectal, and lung cancer share some degree of genetic basis. Cancer Epidemiol Biomarkers Prev; 26(9); 1427–35. ©2017 AACR.
Data from Melanoma Genetic Testing, Counseling, and Adherence to Skin Cancer Prevention and Detection Behaviors
Authors: Glanz Karen , Volpicelli Kathryn , Kanetsky Peter A. , Ming Michael E. , Schuchter Lynn M. , Jepson Christopher , Domchek Susan M. , Armstrong Katrina
Published: April 2023

Abstract
Background: Little is known about the impact of knowledge of CDKN2A and MC1R genotype on melanoma prevention behaviors like sun avoidance and skin examination in the context of familial melanoma.

Methods: Seventy-three adults with a family history of melanoma were randomly assigned to be offered individualized CDKN2A and MC1R genotyping results in the context of a genetic counseling session, or the standard practice of not being offered counseling or disclosure of genotyping results. Mixed effects or longitudinal logistic models were used to determine whether the intervention affected change in sun protection habits, skin examinations, and perception and beliefs related to melanoma risk, prevention, and genetic counseling.

Results: All participants in the intervention group who attended genetic counseling sessions chose to receive their test results. From baseline to follow-up, participants in the intervention group reported an increase in the frequency of skin self-examinations compared with a slight decrease in the control group (P = 0.002). Participants in the intervention group reported a smaller decrease in frequency of wearing a shirt with long sleeves than did participants in the control group (P = 0.047). No effect of the intervention was noted for other outcomes.

Conclusions: Feedback of CDKN2A and MC1R genotype among families without known pathogenic CDKN2A mutations does not seem to decrease sun protection behaviors.

Impact: While disclosure of CDKN2A and MC1R genotype did not have negative effects on prevention, the benefits of communicating this information remain unclear. The small number of families who tested positive for CDKN2A mutations in this study is a limitation. Cancer Epidemiol Biomarkers Prev; 22(4); 607–14. ©2013 AACR.
Data from The Applicability of the International Classification of Functioning, Disability, and Health to Study Lifestyle and Quality of Life of Colorectal Cancer Survivors
Authors: van Roekel Eline H. , Bours Martijn J.L. , de Brouwer Carin P.M. , Ten Napel Huib , Sanduleanu Silvia , Beets Geerard L. , Kant IJmert , Weijenberg Matty P.
Published: April 2023

Abstract
Background: Well-designed studies on lifestyle and health-related quality of life (HRQoL) in colorectal cancer survivors based on a biopsychosocial instead of a traditional biomedical approach are warranted. We report on the applicability of the International Classification of Functioning, Disability, and Health (ICF) as useful biopsychosocial framework to improve research on how lifestyle influences colorectal cancer survivors' HRQoL, using the Energy for life after ColoRectal cancer (EnCoRe) study as an example.

Methods: The ICF was used to develop a conceptual model for studying lifestyle and colorectal cancer survivors' HRQoL, by identifying relevant factors from literature and mapping them within the ICF. Subsequently, this model was used for selection of measurement instruments and biomarkers. By linking meaningful concepts within selected measures to the ICF, we could assess the ICF coverage of our developed conceptual model.

Results: Within selected measures, 450 meaningful concepts were identified, of which 88% were linked to the ICF. The linking process resulted in 132 distinctive ICF categories assigned (38% within “Body Functions,” 2% within “Body Structures,” 46% within “Activities and Participation,” and 14% within “Environmental Factors”).

Conclusions: The selected EnCoRe study measures broadly cover ICF domains relevant to colorectal cancer survivors, stressing the relevance of using a biopsychosocial approach for studying this population's HRQoL.

Impact: The developed conceptual model will guide data analyses and interpretation, and facilitate early transfer of results for development, evaluation, and implementation of personalized multidisciplinary lifestyle interventions. We recommend the ICF as an invaluable framework for improving the quality and scope of HRQoL studies. Cancer Epidemiol Biomarkers Prev; 23(7); 1394–405. ©2014 AACR.
Data from Rural–Urban Differences in Cancer Incidence and Trends in the United States
Authors: Zahnd Whitney E. , James Aimee S. , Jenkins Wiley D. , Izadi Sonya R. , Fogleman Amanda J. , Steward David E. , Colditz Graham A. , Brard Laurent
Published: April 2023

Abstract
Background: Cancer incidence and mortality rates in the United States are declining, but this decrease may not be observed in rural areas where residents are more likely to live in poverty, smoke, and forego cancer screening. However, there is limited research exploring national rural–urban differences in cancer incidence and trends.

Methods: We analyzed data from the North American Association of Central Cancer Registries' public use dataset, which includes population-based cancer incidence data from 46 states. We calculated age-adjusted incidence rates, rate ratios, and annual percentage change (APC) for: all cancers combined, selected individual cancers, and cancers associated with tobacco use and human papillomavirus (HPV). Rural–urban comparisons were made by demographic, geographic, and socioeconomic characteristics for 2009 to 2013. Trends were analyzed for 1995 to 2013.

Results: Combined cancers incidence rates were generally higher in urban populations, except for the South, although the urban decline in incidence rate was greater than in rural populations (10.2% vs. 4.8%, respectively). Rural cancer disparities included higher rates of tobacco-associated, HPV-associated, lung and bronchus, cervical, and colorectal cancers across most population groups. Furthermore, HPV-associated cancer incidence rates increased in rural areas (APC = 0.724, P < 0.05), while temporal trends remained stable in urban areas.

Conclusions: Cancer rates associated with modifiable risks—tobacco, HPV, and some preventive screening modalities (e.g., colorectal and cervical cancers)—were higher in rural compared with urban populations.

Impact: Population-based, clinical, and/or policy strategies and interventions that address these modifiable risk factors could help reduce cancer disparities experienced in rural populations. Cancer Epidemiol Biomarkers Prev; 27(11); 1265–74. ©2017 AACR.
Data from Modeling of the Growth Kinetics of Occult Breast Tumors: Role in Interpretation of Studies of Prevention and Menopausal Hormone Therapy
Authors: Santen Richard J. , Yue Wei , Heitjan Daniel F.
Published: April 2023

Abstract
Background: Autopsy studies report a reservoir of small, occult, undiagnosed breast cancers in up to 15.6% of women dying from unrelated causes. The effective doubling times (EDT) of these occult neoplasms range from 70 to 350 days and mammographic detection threshold diameters from 0.88 to 1.66 cm. Modeling of the biologic behavior of these occult tumors facilitates interpretation of tamoxifen breast cancer prevention and menopausal hormone therapy studies.

Methods: We used iterative and mathematical techniques to develop a model of occult tumor growth (OTG) whose parameters included prevalence, EDT, and detection threshold. The model was validated by comparing predicted with observed incidence of breast cancer in several populations.

Results: Iterative analysis identified a 200-day EDT, 7% prevalence and 1.16 cm detection threshold as optimal parameters for an OTG model as judged by comparison with Surveillance Epidemiology and End Results (SEER) population incidence rates in the United States. We validated the model by comparing predicted incidence rates with those observed in five separate population databases, in three long-term contralateral breast cancer detection studies, and with data from a computer-simulated tumor growth (CSTG) model. Our model strongly suggests that breast cancer prevention with anti-estrogens or aromatase inhibitors represents early treatment not prevention. In addition, menopausal hormone therapy does not primarily induce de novo tumors but promotes the growth of occult lesions.

Conclusions: Our OGTG model suggests that occult, undiagnosed tumors are prevalent, grow slowly, and are the biologic targets of anti-estrogen therapy for prevention and hormone therapy for menopausal women. Cancer Epidemiol Biomarkers Prev; 21(7); 1038–48. ©2012 AACR.
Data from Health Care Utilization, Lifestyle, and Emotional Factors and Mammography Practices in the Childhood Cancer Survivor Study
Authors: Rosenberg Shoshana M. , Moskowitz Chaya S. , Ford Jennifer S. , Henderson Tara O. , Frazier A. Lindsay , Diller Lisa R. , Hudson Melissa M. , Stanton Annette L. , Chou Joanne F. , Smith Stephanie , Leisenring Wendy M. , Mertens Ann C. , Cox Cheryl L. , Nathan Paul C. , Krull Kevin R. , Robison Leslie L. , Oeffinger Kevin C.
Published: April 2023

Abstract
Background: Women with a history of chest radiotherapy have an increased risk of breast cancer; however, many do not undergo annual recommended screening mammography. We sought to characterize the relationship between mammography and potentially modifiable factors, with the goal of identifying targets for intervention to improve utilization.

Methods: Of 625 female participants sampled from the Childhood Cancer Survivor Study, who were treated with chest radiotherapy, 551 responded to a survey about breast cancer screening practices. We used multivariate Poisson regression to assess several lifestyle and emotional factors, health care practices, and perceived breast cancer risk, in relation to reporting a screening mammogram within the last two years.

Results: Women who had a Papanicolaou test [prevalence ratio (PR): 1.77; 95% confidence interval (CI) 1.26–2.49], and who perceived their breast cancer risk as higher than the average woman were more likely to have had a mammogram (PR, 1.26; 95% CI, 1.09–1.46). We detected an attenuated effect of echocardiogram screening [PR, 0.70; 95% CI (0.52–0.95)] on having a mammogram among older women compared with younger women. Smoking, obesity, physical activity, coping, and symptoms of depression and somatization were not associated with mammographic screening.

Conclusion: Our findings suggest that compliance with routine and risk-based screening can be an important indicator of mammography in childhood cancer survivors. In addition, there is a need to ensure women understand their increased breast cancer risk, as a means to encouraging them to follow breast surveillance guidelines.

Impact: Screening encounters could be used to promote mammography compliance in this population. Cancer Epidemiol Biomarkers Prev; 24(11); 1699–706. ©2015 AACR.
Data from Using Genetic Proxies for Lifecourse Sun Exposure to Assess the Causal Relationship of Sun Exposure with Circulating Vitamin D and Prostate Cancer Risk
Authors: Bonilla Carolina , Gilbert Rebecca , Kemp John P. , Timpson Nicholas J. , Evans David M. , Donovan Jenny L. , Hamdy Freddie C. , Neal David E. , Fraser William D. , Davey Smith George , Lewis Sarah J. , Lathrop Mark , Martin Richard M.
Published: April 2023

Abstract
Background: Ecological and epidemiological studies have identified an inverse association of intensity and duration of sunlight exposure with prostate cancer, which may be explained by a reduction in vitamin D synthesis. Pigmentation traits influence sun exposure and therefore may affect prostate cancer risk. Because observational studies are vulnerable to confounding and measurement error, we used Mendelian randomization to examine the relationship of sun exposure with both prostate cancer risk and the intermediate phenotype, plasma levels of vitamin D.

Methods: We created a tanning, a skin color, and a freckling score as combinations of single nucleotide polymorphisms that have been previously associated with these phenotypes. A higher score indicates propensity to burn, have a lighter skin color and freckles. The scores were tested for association with vitamin D levels (25-hydroxyvitamin-D and 1,25-dihydroxyvitamin-D) and prostate-specific antigen detected prostate cancer in 3,123 White British individuals enrolled in the Prostate Testing for cancer and Treatment (ProtecT) study.

Results: The freckling score was inversely associated with 25(OH)D levels [change in 25(OH)D per score unit −0.27; 95% CI, −0.52% to −0.01%], and the tanning score was positively associated with prostate cancer risk (OR = 1.05; 95% CI, 1.02–1.09), after adjustment for population stratification and potential confounders.

Conclusions: Individuals who tend to burn are more likely to spend less time in the sun and consequently have lower plasma vitamin D levels and higher susceptibility to prostate cancer.

Impact: The use of pigmentation-related genetic scores is valuable for the assessment of the potential benefits of sun exposure with respect to prostate cancer risk. Cancer Epidemiol Biomarkers Prev; 22(4); 597–606. ©2013 AACR.
Data from Sex Disparities in Cancer Mortality and Survival
Authors: Cook Michael B. , McGlynn Katherine A. , Devesa Susan S. , Freedman Neal D. , Anderson William F.
Published: April 2023

Abstract
Background: Previous research has noted higher cancer mortality rates and lower survival among males than females. However, systematic comparisons of these two metrics by sex have been limited.

Methods: We extracted U.S. vital rates and survival data from the Surveillance, Epidemiology and End Results Database for 36 cancers by sex and age for the period 1977 to 2006. We compared sex-specific mortality rates and examined male-to-female mortality rate ratios (MRR). We also extracted case data which included age and date of diagnosis, sex, primary cancer site, tumor stage and grade, survival time, vital status, and cause of death. Relative cancer-specific HRs for death in the 5-year period following diagnosis were estimated with Cox proportional hazards models, adjusted for covariates.

Results: For the vast majority of cancers, age-adjusted mortality rates were higher among males than females with the highest male-to-female MRR for lip (5.51), larynx (5.37), hypopharynx (4.47), esophagus (4.08), and urinary bladder (3.36). Cancer-specific survival was, for most cancers, worse for males than females, but such disparities were drastically less than corresponding MRRs [e.g., lip (HR = 0.93), larynx (HR = 1.09), hypopharynx (HR = 0.98), esophagus (HR = 1.05), and urinary bladder (HR = 0.83)].

Conclusions: Male-to-female MRRs differed markedly while cancer survival disparities were much less pronounced. This suggests that sex-related cancer disparities are more strongly related to etiology than prognosis.

Impact: Future analytic studies should attempt to understand causes of observed sex disparities in cancer. Cancer Epidemiol Biomarkers Prev; 20(8); 1629–37. ©2011 AACR.
Data from Associations between Testosterone Levels and Incident Prostate, Lung, and Colorectal Cancer. A Population-Based Study
Authors: Hyde Zoë , Flicker Leon , McCaul Kieran A. , Almeida Osvaldo P. , Hankey Graeme J. , Chubb S.A. Paul , Yeap Bu B.
Published: April 2023

Abstract
Background: The relationship between testosterone and cancer is relatively unexplored. We sought to examine whether testosterone and related hormones are associated with incident prostate, lung, and colorectal cancer.

Methods: This was a population-based cohort study. Demographic and clinical predictors of cancer, and testosterone, sex hormone-binding globulin (SHBG), and luteinizing hormone (LH) were measured between 2001 and 2004 in 3,635 community-dwelling men aged 70 to 88 years (mean 77 years). Cancer notifications were obtained via electronic record linkage until December 31, 2010.

Results: During a mean follow-up period of 6.7 ± 1.8 years, there were 297, 104, and 82 cases of prostate, colorectal, and lung cancer. In adjusted competing risks proportional hazards models, each one SD increase in free testosterone was associated with a 9% increase in prostate cancer risk (95% confidence interval [CI], 1.00–1.18), but other hormones were not significantly associated. No significant associations were observed between hormonal parameters and colorectal cancer. Higher total testosterone was associated with lung cancer. Compared with the mean of 15 nmol/L, men with levels of 20 nmol/L were 1.38 times more likely to be cases (95% CI, 1.21–1.57), whereas those with levels of 30 nmol/L were 3.62 times more likely to be cases (95% CI, 2.53–5.18). Higher free testosterone was also associated with lung cancer, though SHBG and LH were not. Associations were maintained after exclusion of current smokers.

Conclusions: Higher free testosterone was associated with incident prostate cancer. Higher testosterone levels may also be associated with lung cancer.

Impact: Further studies should investigate whether these risks apply to men receiving testosterone therapy. Cancer Epidemiol Biomarkers Prev; 21(8); 1319–29. ©2012 AACR.
Data from International Variation in Female Breast Cancer Incidence and Mortality Rates
Authors: DeSantis Carol E. , Bray Freddie , Ferlay Jacques , Lortet-Tieulent Joannie , Anderson Benjamin O. , Jemal Ahmedin
Published: April 2023

Abstract
Background: Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer-related death among women worldwide. Herein, we examine global trends in female breast cancer rates using the most up-to-date data available.

Methods: Breast cancer incidence and mortality estimates were obtained from GLOBOCAN 2012 (globocan.iarc.fr). We analyzed trends from 1993 onward using incidence data from 39 countries from the International Agency for Research on Cancer and mortality data from 57 countries from the World Health Organization.

Results: Of 32 countries with incidence and mortality data, rates in the recent period diverged—with incidence increasing and mortality decreasing—in nine countries mainly in Northern/Western Europe. Both incidence and mortality decreased in France, Israel, Italy, Norway, and Spain. In contrast, incidence and death rates both increased in Colombia, Ecuador, and Japan. Death rates also increased in Brazil, Egypt, Guatemala, Kuwait, Mauritius, Mexico, and Moldova.

Conclusions: Breast cancer mortality rates are decreasing in most high-income countries, despite increasing or stable incidence rates. In contrast and of concern are the increasing incidence and mortality rates in a number of countries, particularly those undergoing rapid changes in human development. Wide variations in breast cancer rates and trends reflect differences in patterns of risk factors and access to and availability of early detection and timely treatment.

Impact: Increased awareness about breast cancer and the benefits of early detection and improved access to treatment must be prioritized to successfully implement breast cancer control programs, particularly in transitioning countries. Cancer Epidemiol Biomarkers Prev; 24(10); 1495–506. ©2015 AACR.
Data from A Randomized Trial to Increase Colonoscopy Screening in Members of High-Risk Families in the Colorectal Cancer Family Registry and Cancer Genetics Network
Authors: Lowery Jan T. , Horick Nora , Kinney Anita Y. , Finkelstein Dianne M. , Garrett Kathleen , Haile Robert W. , Lindor Noralane M. , Newcomb Polly A. , Sandler Robert S. , Burke Carol , Hill Deirdre A. , Ahnen Dennis J.
Published: April 2023

Abstract
Background: Individuals with a strong family history of colorectal cancer have significant risk for colorectal cancer, although adherence to colonoscopy screening in these groups remains low. This study assessed whether a tailored telephone counseling intervention can increase adherence to colonoscopy in members of high-risk families in a randomized, controlled trial.

Methods: Eligible participants were recruited from two national cancer registries if they had a first-degree relative with colorectal cancer under age 60 or multiple affected family members, which included families that met the Amsterdam criteria for hereditary non-polyposis colon cancer (HNPCC), and if they were due for colonoscopy within 24 months. Participants were randomized to receive a tailored telephone intervention grounded in behavioral theory or a mailed packet with general information about screening. Colonoscopy status was assessed through follow-up surveys and endoscopy reports. Cox proportional hazards models were used to assess intervention effect.

Results: Of the 632 participants (ages 25–80), 60% were female, the majority were White, non-Hispanic, educated, and had health insurance. Colonoscopy adherence increased 11 percentage points in the tailored telephone intervention group, compared with no significant change in the mailed group. The telephone intervention was associated with a 32% increase in screening adherence compared with the mailed intervention (HR, 1.32; P = 0.01).

Conclusions: A tailored telephone intervention can effectively increase colonoscopy adherence in high-risk persons. This intervention has the potential for broad dissemination to healthcare organizations or other high-risk populations.

Impact: Increasing adherence to colonoscopy among persons with increased colorectal cancer risk could effectively reduce incidence and mortality from this disease. Cancer Epidemiol Biomarkers Prev; 23(4); 601–10. ©2014 AACR.
Data from Genetic Determinants of 1,3-Butadiene Metabolism and Detoxification in Three Populations of Smokers with Different Risks of Lung Cancer
Authors: Boldry Emily J. , Patel Yesha M. , Kotapati Srikanth , Esades Amanda , Park Sungshim L. , Tiirikainen Maarit , Stram Daniel O. , Le Marchand Loïc , Tretyakova Natalia
Published: April 2023

Abstract
Background: 1,3-Butadiene (BD) is an important carcinogen in tobacco smoke that undergoes metabolic activation to DNA-reactive epoxides. These species can be detoxified via glutathione conjugation and excreted in urine as the corresponding N-acetylcysteine conjugates. We hypothesize that single nucleotide polymorphisms (SNPs) in BD-metabolizing genes may change the balance of BD bioactivation and detoxification in White, Japanese American, and African American smokers, potentially contributing to ethnic differences in lung cancer risk.

Methods: We measured the levels of BD metabolites, 1- and 2-(N-acetyl-L-cysteine-S-yl)-1-hydroxybut-3-ene (MHBMA) and N-acetyl-S-(3,4-dihydroxybutyl)-L-cysteine (DHBMA), in urine samples from a total of 1,072 White, Japanese American, and African American smokers and adjusted these values for body mass index, age, batch, and total nicotine equivalents. We also conducted a genome-wide association study to identify genetic determinants of BD metabolism.

Results: We found that mean urinary MHBMA concentrations differed significantly by ethnicity (P = 4.0 × 10−25). African Americans excreted the highest levels of MHBMA followed by Whites and Japanese Americans. MHBMA levels were affected by GSTT1 gene copy number (P < 0.0001); conditional on GSTT1, no other polymorphisms showed a significant association. Urinary DHBMA levels also differed between ethnic groups (P = 3.3 × 10−4), but were not affected by GSTT1 copy number (P = 0.226).

Conclusions: GSTT1 gene deletion has a strong effect on urinary MHBMA levels, and therefore BD metabolism, in smokers.

Impact: Our results show that the order of MHBMA levels among ethnic groups is consistent with their respective lung cancer risk and can be partially explained by GSTT1 genotype. Cancer Epidemiol Biomarkers Prev; 26(7); 1034–42. ©2017 AACR.
Data from Mapping of the IRF8 Gene Identifies a 3′UTR Variant Associated with Risk of Chronic Lymphocytic Leukemia but not Other Common Non-Hodgkin Lymphoma Subtypes
Authors: Slager Susan L. , Achenbach Sara J. , Asmann Yan W. , Camp Nicola J. , Rabe Kari G. , Goldin Lynn R. , Call Timothy G. , Shanafelt Tait D. , Kay Neil E. , Cunningham Julie M. , Wang Alice H. , Weinberg J. Brice , Norman Aaron D. , Link Brian K. , Leis Jose F. , Vachon Celine M. , Lanasa Mark C. , Caporaso Neil E. , Novak Anne J. , Cerhan James R.
Published: April 2023

Abstract
Background: Our genome-wide association study (GWAS) of chronic lymphocytic leukemia (CLL) identified 4 highly correlated intronic variants within the IRF8 gene that were associated with CLL. These results were further supported by a recent meta-analysis of our GWAS with two other GWAS of CLL, supporting the IRF8 gene as a strong candidate for CLL risk.

Methods: To refine the genetic association of CLL risk, we conducted Sanger sequencing of IRF8 in 94 CLL cases and 96 controls. We then conducted fine mapping by genotyping 39 variants (of which 10 were identified from sequencing) in 745 CLL cases and 1,521 controls. We also assessed these associations with risk of other non-Hodgkin lymphoma (NHL) subtypes.

Results: The strongest association with CLL risk was observed with a common single-nucleotide polymorphism (SNP) located within the 3′ untranslated region (UTR) of IRF8 (rs1044873, log additive OR = 0.7, P = 1.81 × 10−6). This SNP was not associated with the other NHL subtypes (all P > 0.05).

Conclusions: We provide evidence that rs1044873 in the IRF8 gene accounts for the initial GWAS signal for CLL risk. This association appears to be unique to CLL with little support for association with other common NHL subtypes. Future work is needed to assess functional role of IRF8 in CLL etiology.

Impact: These data provide support that a functional variant within the 3′UTR of IRF8 may be driving the GWAS signal seen on 16q24.1 for CLL risk. Cancer Epidemiol Biomarkers Prev; 22(3); 461–6. ©2013 AACR.
Data from Prediagnostic Physical Activity and Colorectal Cancer Survival: Overall and Stratified by Tumor Characteristics
Authors: Hardikar Sheetal , Newcomb Polly A. , Campbell Peter T. , Win Aung Ko , Lindor Noralane M. , Buchanan Daniel D. , Makar Karen W. , Jenkins Mark A. , Potter John D. , Phipps Amanda I.
Published: April 2023

Abstract
Background: Physical activity is associated with a lower incidence of colorectal cancer; however, the relationship of physical activity with colorectal cancer survival is not yet clear. We evaluated the association between prediagnostic physical activity and colorectal cancer survival, overall and accounting for tumor markers associated with colorectal cancer survival: BRAF and KRAS mutation status and microsatellite instability (MSI) status.

Methods: Participants were 20- to 74-year-old colorectal cancer patients diagnosed between 1998 and 2007 from the population-based Seattle Colon Cancer Family Registry (S-CCFR). Self-reported physical activity in the years preceding colorectal cancer diagnosis was summarized as average metabolic equivalent task hours per week (MET-h/wk; n = 1,309). Somatic BRAF and KRAS mutations and MSI status were evaluated on a subset of patients (n = 1043). Cox regression was used to estimate HRs and 95% confidence intervals (CI) for overall and disease-specific survival after adjusting for relevant confounders. Stratified analyses were conducted across categories of BRAF, KRAS, and MSI, as well as tumor stage and site.

Results: Higher prediagnostic recreational physical activity was associated with significantly more favorable overall survival (HR for highest vs. lowest category, 0.70; 95% CI, 0.52–0.96); associations were similar for colorectal cancer–specific survival. Results consistently indicated a favorable association with physical activity across strata defined by tumor characteristics.

Conclusion: Individuals who were physically active before colorectal cancer diagnosis experienced better survival than those who were inactive or minimally active.

Impact: Our results support existing physical activity recommendations for colorectal cancer patients and suggest that the beneficial effect of activity is not specific to a particular molecular phenotype of colorectal cancer. Cancer Epidemiol Biomarkers Prev; 24(7); 1130–7. ©2015 AACR.
Data from Urinary Melatonin in Relation to Postmenopausal Breast Cancer Risk According to Melatonin 1 Receptor Status
Authors: Devore Elizabeth E. , Warner Erica T. , Eliassen A. Heather , Brown Susan B. , Beck Andrew H. , Hankinson Susan E. , Schernhammer Eva S.
Published: April 2023

Abstract
Background: Urinary melatonin levels have been associated with a reduced risk of breast cancer in postmenopausal women, but this association might vary according to tumor melatonin 1 receptor (MT1R) expression.

Methods: We conducted a nested case–control study among 1,354 postmenopausal women in the Nurses' Health Study, who were cancer free when they provided first-morning spot urine samples in 2000 to 2002; urine samples were assayed for 6-sulfatoxymelatonin (aMT6s, a major metabolite of melatonin). Five-hundred fifty-five of these women developed breast cancer before May 31, 2012, and were matched to 799 control subjects. In a subset of cases, immunohistochemistry was used to determine MT1R status of tumor tissue. We used multivariable-adjusted conditional logistic regression to estimate the relative risk (RR) of breast cancer [with 95% confidence intervals (CI)] across quartiles of creatinine-standardized urinary aMT6s level, including by MT1R subtype.

Results: Higher urinary melatonin levels were suggestively associated with a lower overall risk of breast cancer (multivariable-adjusted RR = 0.78; 95% CI = 0.61–0.99, comparing quartile 4 vs. quartile 1; Ptrend = 0.08); this association was similar for invasive vs. in situ tumors (Pheterogeneity = 0.12). There was no evidence that associations differed according to MT1R status of the tumor (e.g., Pheterogeneity for overall breast cancer = 0.88).

Conclusions: Higher urinary melatonin levels were associated with reduced breast cancer risk in this cohort of postmenopausal women, and the association was not modified by MT1R subtype.

Impact: Urinary melatonin levels appear to predict the risk of breast cancer in postmenopausal women. However, future research should evaluate these associations with longer-term follow-up and among premenopausal women. Cancer Epidemiol Biomarkers Prev; 26(3); 413–9. ©2016 AACR.
Data from Biomarker-Based Ovarian Carcinoma Typing: A Histologic Investigation in the Ovarian Tumor Tissue Analysis Consortium
Authors: Köbel Martin , Kalloger Steve E. , Lee Sandra , Duggan Máire A. , Kelemen Linda E. , Prentice Leah , Kalli Kimberly R. , Fridley Brooke L. , Visscher Daniel W. , Keeney Gary L. , Vierkant Robert A. , Cunningham Julie M. , Chow Christine , Ness Roberta B. , Moysich Kirsten , Edwards Robert , Modugno Francesmary , Bunker Clareann , Wozniak Eva L. , Benjamin Elizabeth , Gayther Simon A. , Gentry-Maharaj Aleksandra , Menon Usha , Gilks C. Blake , Huntsman David G. , Ramus Susan J. , Goode Ellen L.
Published: April 2023

Abstract
Background: Ovarian carcinoma is composed of five major histologic types, which associate with outcome and predict therapeutic response. Our aim was to evaluate histologic type assessments across the centers participating in the Ovarian Tumor Tissue Analysis (OTTA) consortium using an immunohistochemical (IHC) prediction model.

Methods: Tissue microarrays (TMA) and clinical data were available for 524 pathologically confirmed ovarian carcinomas. Centralized IHC was conducted for ARID1A, CDKN2A, DKK1, HNF1B, MDM2, PGR, TP53, TFF3, VIM, and WT1, and three histologic type assessments were compared: the original pathologic type, an IHC-based calculated type (termed TB_COSPv2), and a WT1-assisted TMA core review.

Results: The concordance between TB_COSPv2 type and original type was 73%. Applying WT1-assisted core review, the remaining 27% discordant cases subdivided into unclassifiable (6%), TB_COSPv2 error (6%), and original type error (15%). The largest discordant subgroup was classified as endometrioid carcinoma by original type and as high-grade serous carcinoma (HGSC) by TB_COSPv2. When TB_COSPv2 classification was used, the difference in overall survival of endometrioid carcinoma compared with HGSC became significant [RR 0.60; 95% confidence interval (CI), 0.37–0.93; P = 0.021], consistent with previous reports. In addition, 71 cases with unclear original type could be histologically classified by TB_COSPv2.

Conclusions: Research cohorts, particularly those across different centers within consortia, show significant variability in original histologic type diagnosis. Our IHC-based reclassification produced more homogeneous types with respect to outcome than original type.

Impact: Biomarker-based classification of ovarian carcinomas is feasible, improves comparability of results across research studies, and can reclassify cases which lack reliable original pathology. Cancer Epidemiol Biomarkers Prev; 22(10); 1677–86. ©2013 AACR.