bluuebunny/crossref_metadata_2025 huggingface dataset:
Empirical on the Influencing Factors of Local Government’s Online Response
Authors: Lu Teng , Wu Weidong
Published: June 2022

The development of local government online questioning is a practical exploration to promote the digital governance of government. Exploring the influencing factors of local government online questioning response can provide guidance for the governance practice of online questioning. Based on the TOE framework, this paper constructs an analysis model of the influencing factors of local government online questioning response. By using SPSS tools to conduct regression analysis on data from 230 questionnaire samples, the results show five factors: technical competence, high-level support, perceived benefits, public readiness, and public satisfaction to the responsiveness of local government were 0.019, 0.332, 0.265, 0.156, and 0.048, respectively. Therefore, the research conclusion that technical ability, high-level support, perceived benefits, public readiness, and public satisfaction, have a positive impact on local government’s response ability. The analysis of the influencing factors of government’s online in this paper improves the existing research to a certain extent and provides a new path and perspective for the development of network politics in China.
Association between Vitamin D Deficiency and Levels of Renin and Angiotensin in Essential Hypertension
Authors: Han Lu , Xu Xin-Juan , Zhang Jun-Shi , Liu Hai-Ming
Published: June 2022

Objective. The present study aims to investigate the relationship between vitamin D deficiency and renin-angiotensin-aldosterone levels in patients with essential hypertension. Methods. The present study observed two groups of patients from Urumqi, Xinjiang, China, from April 2017 to March 2018. There were two subject groups: the hypertension group (80 patients with essential hypertension selected by random cluster sampling) and the control group (76 healthy adults). The 25-hydroxyvitamin D (25(OH)D or vitamin D) levels were measured through electrolytes; fasting blood glucose, blood lipids, and other biochemical indicators were detected using immune chemiluminescence; and plasma renin activity and angiotensin II concentrations were detected with radio-immunity. Results. Comparison between the hypertension group and control group showed statistically significant differences in the systolic pressure and levels of 25(OH)D, renin, and triglycerides (

P
<
0.05

). The correlation analysis showed that 25(OH)D was negatively correlated with renin (r = –0.185;

P
=
0.021

) and positively correlated with systolic pressure (r = –0.105;

P
=
0.035

). There were no statistically significant differences in diastolic pressure, fasting blood glucose, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides between the two groups. Conclusions. The results of the present study show that vitamin D deficiency is common in Urumqi, Xinjiang, China and vitamin D levels are negatively correlated with renin levels. Vitamin D plays an important role in regulating blood pressure by affecting renin levels through the renin-angiotensin-aldosterone system.
Electricity Procurement Strategies under Supply Disruption and Price Fluctuation
Authors: Tan Jie , Zhong Qin
Published: June 2022

Improving the reliability of electricity supply is closely related to the national industrial economy and people’s livelihood. When procuring electricity, the large consumer faces the risk of insufficient electricity supply. Such insufficiency may be caused by the supply disruption of the upstream electricity generator and the fluctuation of electricity prices in the electricity pool. We establish an expected cost model for the large consumer and a revenue model for the electricity generator by introducing robustness and opportunity functions to analyse the impact of supply disruption and price fluctuation on both members. Then, we obtain the optimal reliability level and subsidy rate. Our analytical results reveal the following points: (1) During an electricity price fluctuation, the sufficient and necessary condition for the large consumer to expect high robustness of his own decision‐making is to pay a high cost. (2) The high uncertainty of electricity price leads to less revenue for the electricity generator; thus, the electricity generator should perform well in price forecasting. (3) Without disruption risk, the electricity generator is reliable. Furthermore, the electricity pool is unreliable from the perspective of price. However, the electricity supply of the electricity generator is no longer reliable when considering disruption risk, whereas the electricity pool is reliable because the large consumer is tolerant of price fluctuation under this circumstance. Moreover, the impacts of market uncertainty and players’ attributes on the optimal strategies are explored.
On the Secrecy Outage Performance of Cooperative NOMA-Assisted Hybrid Satellite-Terrestrial Networks
Authors: Li Bingjing , Xu Ding , Chen Bailing , Ahmad Ishtiaq
Published: June 2022

This paper investigates the secrecy outage performance of a downlink cooperative nonorthogonal multiple access- (NOMA-) assisted hybrid satellite-terrestrial network, where a satellite source communicates with two terrestrial users based on NOMA, in the presence of a terrestrial eavesdropper. We assume that there is no direct link between the satellite source and the far terrestrial user, and the near terrestrial user acts as a relay to forward the information to the far terrestrial user. The near user is assumed to support both half-duplex mode and the full-duplex mode for information relaying. We derive the closed-form exact expressions for the secrecy outage probability (SOP) of the near user, as well as the closed-form approximate expressions for the SOP of the far user based on the Gaussian-Chebyshev quadrature. Theoretical results are validated by conducting simulations. The impacts of various system parameters on the performance comparison between the half-duplex mode and full-duplex mode are investigated. Particularly, the full-duplex mode is shown to outperform the half-duplex mode when the received signal-to-noise ratio (SNR) at the near user is low or the residual self-interference is low.
Longitudinal Changes in Lifestyle Behaviors and Health Status in Colon Cancer Survivors
Authors: Satia Jessie A. , Campbell Marci K. , Galanko Joseph A. , James Aimee , Carr Carol , Sandler Robert S.
Published: June 2022

Lifestyle changes in persons diagnosed with cancer are important because they may impact prognosis, co-morbidities, and survival. This report describes longitudinal changes in lifestyle behaviors and health status among colon cancer survivors (n = 278) and population-based controls (n = 459) in North Carolina (39% African American), and examines demographic and psychosocial correlates of healthy lifestyle changes following a colon cancer diagnosis. Data are from surveys of a population-based cohort of colon cancer patients on diagnosis (the North Carolina Colon Cancer Study, NCCCS) and approximately 2 years post-diagnosis [the North Carolina Strategies to Improve Diet, Exercise, and Screening Study (NC STRIDES)], and population-based controls. Both studies collected information on demographic/lifestyle characteristics and medical history. The NCCCS reflects pre-diagnosis or pre-interview patterns, whereas NC STRIDES queried on current practices. Between the NCCCS and NC STRIDES, colon cancer survivors reported significant increases in vegetable intake, physical activity, and supplement use (all P <0.01) and a non-statistically significant increase in fruit/juice consumption (0.1 serving), with larger fruit/vegetable changes in African Americans than Whites. Controls increased physical activity and supplement use and fewer reported arthritic symptoms (P < 0.05). Survivors who were older and female had an almost 3 times higher likelihood of having used at least one new dietary supplement post-diagnosis, whereas being retired correlated with increased vegetable intake, all P < 0.05. Having more barriers to increasing fruit/vegetable intake was inversely associated with taking a new supplement (P < 0.05 only in controls). Colon cancer survivors reported making significant improvements in multiple health-related behaviors. Health care providers should communicate with persons diagnosed with colon cancer to ensure that they are making healthy lifestyle changes.
WBC Count and the Risk of Cancer Mortality in a National Sample of U.S. Adults: Results from the Second National Health and Nutrition Examination Survey Mortality Study
Authors: Erlinger Thomas P. , Muntner Paul , Helzlsouer Kathy J.
Published: June 2022

Inflammation has been shown to be a risk factor for several chronic diseases. Few epidemiologic studies have examined the relationship between markers of inflammation and cancer. The current study included 7,674 Second National Health and Nutrition Examination Survey (NHANES II) participants, 30 to 74 years of age, between 1976 and 1980. Mortality follow-up through December 31, 1992 was assessed using the National Death Index and Social Security Administration Death Master File. A graded association between higher WBC and higher risk of total cancer mortality was observed [highest versus lowest quartile (relative risk [RR] 2.23; 95% confidence interval [CI], 1.53-3.23)] after adjusting for age, sex, and race. After further adjustment for smoking, physical activity, body mass index, alcohol intake, education, hematocrit, and diabetes, WBC remained significantly associated (P trend = 0.03) with total cancer mortality [highest versus lowest quartile (RR 1.66; 95% CI, 1.08-2.56)]. In stratified analyses, increased WBC was associated with higher risk of non-lung cancer (P trend = 0.04), but not lung cancer (P trend = 0.18). Among never smokers, a 1 SD increase in WBC (2.2 × 109 cells/L) was associated with greater risk of total (RR 1.32; 95% CI, 1.05-1.67) and non-lung (RR 1.30; 95% CI, 1.03-1.63) cancer mortality. These findings support the hypothesis that inflammation is an independent risk factor for cancer mortality. Additional studies are needed to determine whether circulating levels of inflammatory markers are associated with increased risk of incident cancer.
Reliability and Validity of Opiate Use Self-Report in a Population at High Risk for Esophageal Cancer in Golestan, Iran
Authors: Abnet Christian C. , Saadatian-Elahi Mitra , Pourshams Akram , Boffetta Paolo , Feizzadeh Ali , Brennan Paul , Taylor Philip R. , Kamangar Farin , Dawsey Sanford M. , Malekzadeh Reza
Published: June 2022

Objective: To assess the reliability and validity of self-reported opium use in a rural Iranian population at high risk for esophageal cancer in preparation for a large cohort study. Method: 1,057 subjects ages 33 to 84 years were recruited from Gonbad city and three surrounding villages in Golestan province of Iran and completed a questionnaire and provided biological samples. The history and duration of using opium, smoking tobacco, chewing nass, and drinking alcohol were measured by questionnaire in the entire cohort. A subgroup of 130 people was reinterviewed after 2 months to assess reliability. Validity of the opium question was assessed by comparing the questionnaire responses with the presence of codeine and morphine in the urine of 150 selected subjects. Results: Self-reported opiate use is reliable and valid in this population. The reliability of ever opium use and duration of opium use had κ's of 0.96 and 0.74, respectively. The validity of self-reported opium use was also high. Using urine codeine or morphine as the gold standard for use of opium, self-report had a sensitivity of 0.93 and a specificity of 0.89. Conclusions: The self-reported use of opium can provide a reliable and valid measurement in this population and will be useful for studying associations between opium use and occurrence of esophageal cancer and other diseases.
Insulin, Macronutrient Intake, and Physical Activity: Are Potential Indicators of Insulin Resistance Associated with Mortality from Breast Cancer?
Authors: Borugian Marilyn J. , Sheps Samuel B. , Kim-Sing Charmaine , Van Patten Cheri , Potter John D. , Dunn Bruce , Gallagher Richard P. , Hislop T. Gregory
Published: June 2022

High levels of insulin have been associated with increased risk of breast cancer, and poorer survival after diagnosis. Data and sera were collected from 603 breast cancer patients, including information on diet and physical activity, medical history, family history, demographic, and reproductive risk factors. These data were analyzed to test the hypothesis that excess insulin and related factors are directly related to mortality after a diagnosis of breast cancer. The cohort was recruited from breast cancer patients treated at the British Columbia Cancer Agency between July 1991 and December 1992. Questionnaire and medical record data were collected at enrolment and outcomes were ascertained by linkage to the BC Cancer Registry after 10 years of follow-up. The primary outcome of interest was breast cancer-specific mortality (n = 112). Lifestyle data were analyzed using Cox proportional hazards regression models to relate risk factors to outcomes, controlling for potential confounders, such as age and stage at diagnosis. Data for biological variables were analyzed as a nested case-control study due to limited serum volumes, with at least one survivor from the same cohort as a control for each breast cancer death, matched on stage and length of follow-up. High levels of insulin were associated with poorer survival for postmenopausal women [odds ratio, 1.9; 95% confidence interval (CI), 0.7-6.6, comparing highest to lowest tertile, P trend = 0.10], while high dietary fat intake was associated with poorer survival for premenopausal women (relative risk, 4.8; 95% CI, 1.3-18.1, comparing highest to lowest quartile). Higher dietary protein intake was associated with better survival for all women (relative risk, 0.4; 95% CI, 0.2-0.8, comparing highest to lowest quartile).
Lysophospholipids Are Potential Biomarkers of Ovarian Cancer
Authors: Sutphen Rebecca , Xu Yan , Wilbanks George D. , Fiorica James , Grendys Edward C. , LaPolla James P. , Arango Hector , Hoffman Mitchell S. , Martino Martin , Wakeley Katie , Griffin David , Blanco Rafael W. , Cantor Alan B. , Xiao Yi-jin , Krischer Jeffrey P.
Published: June 2022

Objective: To determine whether lysophosphatidic acid (LPA) and other lysophospholipids (LPL) are useful markers for diagnosis and/or prognosis of ovarian cancer in a controlled setting. Method: Plasma samples were collected from ovarian cancer patients and healthy control women in Hillsborough and Pinellas counties, Florida, and processed at the University of South Florida H. Lee Moffitt Cancer Center and Research Institute (Moffitt). Case patients with epithelial ovarian cancer (n = 117) and healthy control subjects (n = 27) participated in the study. Blinded LPL analysis, including 23 individual LPL species, was performed at the Cleveland Clinic Foundation using an electrospray ionization mass spectrometry–based method. LPL levels were transmitted to Moffitt, where clinical data were reviewed and statistical analyses were performed. Results: There were statistically significant differences between preoperative case samples (n = 45) and control samples (n = 27) in the mean levels of total LPA, total lysophosphatidylinositol (LPI), sphingosine-1-phosphate (S1P), and individual LPA species as well as the combination of several LPL species. The combination of 16:0-LPA and 20:4-LPA yielded the best discrimination between preoperative case samples and control samples, with 93.1% correct classification, 91.1% sensitivity, and 96.3% specificity. In 22 cases with both preoperative and postoperative samples, the postoperative levels of several LPL, including S1P, total LPA, and lysophosphatidylcholine (LPC) levels and some individual species of LPA and LPC, were significantly different from preoperative levels. Conclusion: LPA, LPI, LPC, and S1P appear useful as diagnostic and prognostic biomarkers of ovarian cancer.
Glycemic Index, Glycemic Load, and Carbohydrate Intake in Relation to Risk of Distal Colorectal Adenoma in Women
Authors: Oh Kyungwon , Willett Walter C. , Fuchs Charles S. , Giovannucci Edward L.
Published: June 2022

Case-control studies and a cohort study have shown inconsistent associations between a high glycemic index or a high glycemic load and risk of colorectal cancer. These dietary variables have not been examined in relation to risk of colorectal adenoma. We thus examined the associations between dietary glycemic index, glycemic load, and carbohydrate intake with risk of adenoma of the distal colon or rectum among 34,428 US women who were initially free of cancer or polyps, who completed a semi-quantitative food-frequency questionnaire in 1980, and who underwent endoscopy from 1980 through 1998. 1,715 adenoma cases (704 large adenomas, 894 small adenomas, 1,277 distal colon adenomas, and 504 rectal adenomas) were documented during 18 years of follow-up. Dietary glycemic index, glycemic load, and carbohydrate intake were not related to risk of total colorectal adenoma after adjustment for age and established risk factors [relative risk (RR) for extreme quintiles of glycemic index = 1.11, 95% confidence interval (CI) 0.94-1.32, P for trend = 0.66; RR for glycemic load = 0.92, 95% CI 0.76-1.11, P for trend = 0.63; RR for carbohydrate intake = 0.90, 95% CI 0.73-1.11, P for trend = 0.64]. In addition, no significant associations were found for large or small adenoma, distal colon or rectal adenoma, or across strata of body mass index. Our findings do not support the hypothesis that a high glycemic index diet, a high glycemic load diet, or high carbohydrate intake overall are associated with risk of colorectal adenoma.
XPD Polymorphism and Risk of Subsequent Cancer in Individuals with Nonmelanoma Skin Cancer
Authors: Brewster Abenaa M. , Alberg Anthony J. , Strickland Paul T. , Hoffman Sandy C. , Helzlsouer Kathy
Published: June 2022

Background: Individuals with nonmelanoma skin cancer (NMSC) are at increased risk of developing subsequent cancers. Genetic predisposition to reduced DNA repair capacity may be an underlying susceptibility factor explaining the excess risk of malignancies. To test this hypothesis, a cohort study was conducted to examine the association between XPD Lys751Gln polymorphism and risk of a second primary cancer in individuals with NMSC. Methods: A subgroup of 481 individuals with a history of NMSC who participated in the CLUE II community-based cohort was followed for the development of a second primary cancer. Blood specimens donated in 1989 were genotyped for the XPD Lys751Gln polymorphism using the 5′ nuclease assay. Cox proportional regression with delayed entry was used to calculate the incidence rate ratio (IRR) and 95% confidence interval (95% CI) for risk of developing a second primary cancer according to XPD genotype. All statistical tests were two sided. Results: Eighty individuals developed a second primary cancer. The most frequent occurring cancers were of the prostate (18%), lung (15%), and breast (15%). Persons with at least one Gln allele had an increased risk of a second primary cancer compared with the reference Lys/Lys genotype (adjusted IRR 2.22, 95% CI 1.30-3.76). When the reference category was limited to never smokers with the Lys/Lys genotype, the risk of developing a second primary cancer associated with having at least one Gln allele was increased >3-fold in both never smokers (IRR 3.93, 95% CI 1.36-11.36) and ever smokers (IRR 6.14, 95% CI 2.17-17.37). Conclusion: These findings suggest that individuals with NMSC who have the variant XPD Gln allele are at increased risk of developing a second primary cancer.
Diabetes Mellitus and Subsite-Specific Colorectal Cancer Risks in the Iowa Women's Health Study
Authors: Limburg Paul J. , Anderson Kristin E. , Johnson Trista W. , Jacobs David R. , Lazovich DeAnn , Hong Ching-Ping , Nicodemus Kristin K. , Folsom Aaron R.
Published: June 2022

Objective: Controversy remains regarding the association between type 2 diabetes mellitus (DM) and colorectal cancer (CRC) risk. To clarify and extend the existing data, we prospectively evaluated the association between self-reported type 2 DM (onset at >30 years of age) and incident CRC, overall and by anatomic subsite, among postmenopausal women in the Iowa Women's Health Study (n = 35,230).

Methods: After 14 years of follow-up, a total of 870 incident CRC cases were identified through annual linkage to the Iowa Cancer Registry. DM was analyzed as reported at baseline and as a time-dependent variable using information obtained during follow-up. CRC risks were estimated using Cox proportional hazards regression models.

Results: After adjusting for age, body mass index and other potential confounding variables, the relative risk (RR) for women with DM versus women without DM was modestly increased at 1.4 [95% confidence interval (95% CI), 1.1-1.8]. By anatomic subsite, the RR for proximal colon cancer was statistically significantly increased (RR, 1.9; 95% CI, 1.3-2.6), whereas the RRs for distal colon (RR, 1.1; 95% CI, 0.6-1.8) and rectal cancer (RR, 0.8; 95% CI, 0.4-1.6) were not statistically different from unity. Analyses that included DM ascertained at baseline and follow-up yielded similar results.

Conclusion: In this large, prospective study of postmenopausal women, the association between DM and incident CRC was found to be subsite specific. If confirmed by others, this finding implies that CRC prevention strategies among type 2 DM patients should include examination of the proximal colon.
Cytochrome P450 1A1 Polymorphism and Childhood Leukemia: An Analysis of Matched Pairs Case-Control Genotype Data
Authors: Selvin Steve
Published: June 2022

The association between the genotypic frequencies of the cytochrome P450 1A1 polymorphism and the risk of childhood leukemia is explored with the data from a matched case-control study. The data are displayed in a 3 × 3 case-control array, and the discordant pair counts are assessed for quasi-independence, homogeneity, and symmetry. This statistical approach is contrasted to the more typical analysis of matched data based on a conditional logistic model and estimated odds ratios. The statistical analysis of 175 matched pairs (part of a large study of potential environmental/genetic influences on the risk of childhood leukemia) showed no evidence of an association between cytochrome P450 1A1 genotype frequencies and case-control status.
Serologic Assessment of Type 1 and Type 2 Immunity in Healthy Japanese Adults
Authors: Birmann Brenda M. , Mueller Nancy , Okayama Akihiko , Hsieh Chung-Cheng , Tachibana Nobuyoshi , Tsubouchi Hirohito , Lennette Evelyne T. , Harn Donald , Stuver Sherri
Published: June 2022

We assessed the informativeness of several serologic biomarkers of immune function using serum specimens collected in the Miyazaki Cohort Study from subjects who were seronegative for anti–human T-cell lymphotrophic virus I and anti–hepatitis C virus. To broadly characterize type 1 immune status, we measured EBV antibody titers, because titer profiles associated with cellular immune suppression are well described. We also tested for three type 2 biomarkers: total serum IgE, soluble CD23, and soluble CD30. Nonreactivity to a tuberculin purified protein derivative (PPD) skin test is indicative of diminished delayed-type hypersensitivity (type 1) responsiveness in the study population due to a history of tuberculosis exposure or Bacillus Calmette-Guérin vaccination. We therefore evaluated the serologic markers as predictors of PPD nonreactivity using logistic regression. Subjects whose EBV antibody profiles were consistent with deficient type 1 immunity were more than thrice as likely to be PPD nonreactive as persons with “normal” antibody titers. Elevated total IgE was also strongly associated with PPD nonreactivity (odds ratio 3.4, 95% confidence interval 1.2-9.9); elevated soluble CD23 had a weaker, but positive, odds ratio, whereas soluble CD30 levels were not predictive of PPD status. Therefore, PPD nonreactivity is associated, in this population, with a pattern of serum biomarkers that is indicative of diminished type 1 and elevated type 2 immunity. We conclude that, with the exception of soluble CD30, the serologic markers are informative for the characterization of type 1/type 2 immune status using archived sera from study populations of healthy adults.
Raw versus Cooked Vegetables and Cancer Risk
Authors: Link Lilli B. , Potter John D.
Published: June 2022

This review of the medical literature from 1994 to 2003 summarizes the relationship between raw and cooked vegetables and cancer risk and examines whether they may affect cancer risk differently. Twenty-eight studies examined the relationship between raw and cooked vegetables and risk for various cancers. Twenty-one studies assessed raw, but not cooked, vegetables and cancer risk. The majority of these assessed risk of oral, pharyngeal, laryngeal, esophageal, lung, gastric, and colorectal cancers. Most showed that vegetables, raw or cooked, were inversely related to these cancers. However, more consistent results were found for oral, pharyngeal, laryngeal, esophageal, and gastric cancers. Nine of the 11 studies of raw and cooked vegetables showed statistically significant inverse relationships of these cancers with raw vegetables, but only 4 with cooked vegetables. The few studies of breast, lung, and colorectal cancers also suggested an inverse relationship with both raw and cooked vegetables, but these results were less consistent. In the two studies of prostate cancer, there was no association with either raw or cooked vegetables. One of two bladder cancer studies found an inverse relationship with cooked, but not raw, vegetables. Possible mechanisms by which cooking affects the relationship between vegetables and cancer risk include changes in availability of some nutrients, destruction of digestive enzymes, and alteration of the structure and digestibility of food. Both raw and cooked vegetable consumption are inversely related to epithelial cancers, particularly those of the upper gastrointestinal tract, and possibly breast cancer; however, these relationships may be stronger for raw vegetables than cooked vegetables.
Vitamin D, Calcium, and Mammographic Breast Densities
Authors: Bérubé Sylvie , Diorio Caroline , Verhoek-Oftedahl Wendy , Brisson Jacques
Published: June 2022

Vitamin D and calcium are being evaluated as potential breast cancer prevention agents. This study reports on the relation of dietary vitamin D and calcium to mammographic breast densities, one of the strongest breast cancer risk factors. Participants were women ages 40 to 60 years who had had a screening mammogram in Rhode Island and eastern Massachusetts (1989–1990). Diet was assessed by semiquantitative food frequency questionnaire, and the percentage of the breast showing densities was estimated visually by a single observer without information on subjects. Multivariate logistic regression was used to compare dietary intakes of vitamin D and calcium between women classified as having few densities (≤30% of the breast with density, n = 287) and extensive densities (≥70% of the breast with density, n = 256). For categories of increasing vitamin D intake (<50, 50–99, 100–199, and ≥200 IU/d), adjusted odds ratios (OR) for extensive densities were 1.00 (reference), 0.51, 0.37, and 0.24, respectively (P for trend = 0.0005). For increasing calcium intake (<500, 500–749, 750–999, and ≥1,000 mg/d), adjusted ORs were 1.00 (reference), 0.63, 0.25, and 0.24, respectively (P for trend = 0.0006). Combination of higher intakes of vitamin D and calcium (≥100 IU/d and ≥750 mg/d, respectively) were associated with a reduction of breast densities (OR, 0.28; 95% confidence interval, 0.15–0.54) compared with those consuming <100 IU/d and <750 mg/d. Increases in vitamin D and calcium intakes were associated with decreases in breast densities, suggesting that dietary vitamin D and calcium could reduce breast cancer risk possibly through influences on breast tissue morphology.
Glutathione S-transferases M1, T1, and P1 and Breast Cancer: A Pooled Analysis
Authors: Vogl Florian D. , Taioli Emanuela , Maugard Christine , Zheng Wei , Ribeiro Pinto Luis F. , Ambrosone Christine , Parl Fritz F. , Nedelcheva-Kristensen Vessela , Rebbeck Timothy R. , Brennan Paul , Boffetta Paolo
Published: June 2022

The glutathione S-transferase (GST) genes are involved in the metabolism of various carcinogens. Deletion polymorphisms in the genes GSTM1 and GSTT1 and a base transition polymorphism at codon 105 (Ile→Val) in GSTP1 were investigated in relation to breast cancer risk. Tobacco smoking and reproductive factors were examined as potential effect modifiers. Individual data from seven case-control studies were pooled within the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens. To measure the effect of GSTs on breast cancer risk, odds ratios and 95% confidence intervals were computed adjusting for study center and age. The modifying effect was investigated by stratification on variables of smoking habits and reproductive history. A total of 2,048 cases with breast cancer and 1,969 controls were analyzed. The relative odds ratio (95% confidence interval) of breast cancer was 0.98 (0.86–1.12) with the GSTM1 null, 1.11 (0.87–1.41) with the GSTT1 null, 1.01 (0.79–1.28) with GSTP1 heterozygous mutants, and 0.93 (0.62–1.38) with GSTP1 homozygous mutants. Stratification by smoking or reproductive factors did not reveal a modifying effect of these variables, nor was there any association between GSTM1 and age at diagnosis of breast cancer. This is the largest study investigating susceptibility to breast cancer due to polymorphisms in the GST genes. The results conclusively show that single gene GST polymorphisms do not confer a substantial risk of breast cancer to its carriers. Furthermore, GSTs did not interact with smoking or reproductive history to modify cancer risk.
Red Meat, Chicken, and Fish Consumption and Risk of Colorectal Cancer
Authors: English Dallas R. , MacInnis Robert J. , Hodge Allison M. , Hopper John L. , Haydon Andrew M. , Giles Graham G.
Published: June 2022

Background: Red meat and processed meat consumption have been associated with increased risk of colorectal cancer in some, but not all, relevant cohort studies. Evidence on the relationship between risk of colorectal cancer and poultry and fish consumption is inconsistent. Methods: We conducted a prospective cohort study of 37,112 residents of Melbourne, Australia recruited from 1990 to 1994. Diet was measured with a food frequency questionnaire. We categorized the frequency of fresh red meat, processed meat, chicken, and fish consumption into approximate quartiles. Adenocarcinomas of the colon or rectum were ascertained via the Victorian Cancer Registry. Results: We identified 283 colon cancers and 169 rectal cancers in an average of 9 years of follow-up. For rectal cancer, the hazard ratios [95% confidence intervals (95% CI)] in the highest quartile of consumption of fresh red meat and processed meat were 2.3 (1.2–4.2; P for trend = 0.07) and 2.0 (1.1–3.4; P for trend = 0.09), respectively. The corresponding hazard ratios (95% CIs) for colon cancer were 1.1 (0.7–1.6; P for trend = 0.9) and 1.3 (0.9–1.9; P for trend = 0.06). However, for neither type of meat was the heterogeneity between subsites significant. Chicken consumption was weakly negatively associated with colorectal cancer (hazard ratio highest quartile, 0.7; 95% CI, 0.6–1.0; P for trend = 0.03), whereas hazard ratios for fish consumption were close to unity. Conclusion: Consumption of fresh red meat and processed meat seemed to be associated with an increased risk of rectal cancer. Consumption of chicken and fish did not increase risk.
Microsomal Epoxide Hydrolase Polymorphisms and Risk for Advanced Colorectal Adenoma
Authors: Huang Wen-Yi , Chatterjee Nilanjan , Chanock Stephen , Dean Michael , Yeager Meredith , Schoen Robert E. , Hou Li-Fang , Berndt Sonja I. , Yadavalli Sunita , Johnson Christine C. , Hayes Richard B.
Published: June 2022

Cigarette smoking is a risk factor for colorectal adenoma, a precursor of colorectal cancer. Microsomal epoxide hydrolase (EPHX1) metabolizes polycyclic aromatic hydrocarbons, carcinogens found in cigarette smoke. Nonsynonymous variants of EPHX1 at Tyr113His (exon 3) and His139Arg (exon 4) are associated, respectively, with low (113His) and high (139Arg) predicted activity. Among participants randomized to the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, we evaluated risks for advanced adenoma in relation to cigarette use and these two EPHX1 variants. We compared 772 cases with advanced adenoma (adenoma ≥1 cm or containing high-grade dysplasia or villous, including tubulovillous, elements) of the distal colon (left-sided, descending colon and sigmoid or rectum) to 777 gender- and age-matched controls who were screen-negative for left-sided adenoma. Compared to those with homozygous genotypes predicting low EPHX1 activity, advanced adenoma risks tended to be elevated for carriers of 113TyrTyr [odds ratios (OR), 1.5; 95% confidence intervals (CI), 1.0-2.2] and 139ArgArg (OR, 1.4; 95% CI, 0.8-2.5) and for subjects who carried a greater number of the alleles (113Tyr or 139Arg) associated with high predicted enzymatic activity (Ptrend = 0.03). The increased risk associated with the increasing number of putative high-activity alleles was most apparent among current and recent (quit <10 years) cigarette smokers (Ptrend = 0.02). In conclusion, EPHX1 variants at codon 113 and 139 associated with high predicted enzymatic activity appear to increase risk for colorectal adenoma, particularly among recent and current smokers.
Impact of Misclassification in Genotype-Exposure Interaction Studies: Example of N-Acetyltransferase 2 (NAT2), Smoking, and Bladder Cancer
Authors: Deitz Anne C. , Rothman Nathanial , Rebbeck Timothy R. , Hayes Richard B. , Chow Wong-Ho , Zheng Wei , Hein David W. , García-Closas Montserrat
Published: June 2022

Errors in genotype determination can lead to bias in the estimation of genotype effects and gene-environment interactions and increases in the sample size required for molecular epidemiologic studies. We evaluated the effect of genotype misclassification on odds ratio estimates and sample size requirements for a study of NAT2 acetylation status, smoking, and bladder cancer risk. Errors in the assignment of NAT2 acetylation status by a commonly used 3-single nucleotide polymorphism (SNP) genotyping assay, compared with an 11-SNP assay, were relatively small (sensitivity of 94% and specificity of 100%) and resulted in only slight biases of the interaction parameters. However, use of the 11-SNP assay resulted in a substantial decrease in sample size needs to detect a previously reported NAT2-smoking interaction for bladder cancer: 1,121 cases instead of 1,444 cases, assuming a 1:1 case-control ratio. This example illustrates how reducing genotype misclassification can result in substantial decreases in sample size requirements and possibly substantial decreases in the cost of studies to evaluate interactions.
Incidence of Invasive Breast Cancer and Ductal Carcinoma In situ in a Screening Program by Age: Should Older Women Continue Screening?
Authors: Erbas Bircan , Amos Alison , Fletcher Ashley , Kavanagh Anne M. , Gertig Dorota M.
Published: June 2022

Objective: The evidence for the effectiveness of screening is strongest for women ages 50 to 69 years; however, there is variation in the target age group for screening programs between different countries. In particular, there is uncertainty over whether women should continue screening once they reach age 70. We therefore investigated incidence rates for invasive and in situ breast cancer by age as well as prognostic features of tumors within a screening program. Methods: We studied 474,808 women who attended BreastScreen Victoria from January 1, 1993 to December 31, 2000. Of these women, 5,301 were diagnosed with invasive cancer and 1,127 were diagnosed with ductal carcinoma in situ. We used generalized additive models to model age-incidence rates for invasive cancers and ductal carcinoma in situ separately by users and nonusers of hormone replacement therapy at most recent screen. Nonparametric trends for ordered groups and regression methods were used to investigate trends in size, grade, and nodal involvement for invasive tumors by type of attendance and time since previous negative screen for age group. Results: The incidence of ductal carcinoma in situ among women with a previous negative screen clearly declined after age 70 irrespective of hormone replacement therapy use. At subsequent screen, the age-incidence curve for invasive breast cancer flattened at ages 60 to 75 years and then increased only for women taking hormone replacement therapy. Tumor size at diagnosis declined with age at both first round (P = 0.15) and subsequent round (P = 0.08). The proportion of poorly differentiated tumors also decreased with age, with the smallest proportion of grade III tumors diagnosed in women ages ≥75 years (P = 0.09 for first screen and P = 0.05 for subsequent screen). The presence of positive nodes at diagnosis declined with age (P < 0.001) for both first and subsequent screening rounds. Conclusion: Older age is associated with more favorable prognostic tumor features and a lower incidence of ductal carcinoma in situ among subsequent attenders of screening. When making decisions regarding continuing screening, older women and their physicians should also consider the presence of other comorbid conditions that may mitigate any impact of screening on mortality.
STK15 Polymorphisms and Association with Risk of Invasive Ovarian Cancer
Authors: DiCioccio Richard A. , Song Honglin , Waterfall Christy , Kimura Makoto T. , Nagase Hiroki , McGuire Valerie , Hogdall Estrid , Shah Mitul N. , Luben Robert N. , Easton Douglas F. , Jacobs Ian J. , Ponder Bruce A.J. , Whittemore Alice S. , Gayther Simon A. , Pharoah Paul D.P. , Kruger-Kjaer Susan
Published: June 2022

STK15 is a putative oncogene that codes for a centrosome-associated, serine/threonine kinase, the normal function of which is to ensure accurate segregation of chromosomes during mitosis. Amplification of STK15 has been reported in ovarian tumors, suggesting a role in ovarian cancer pathology. STK15 is polymorphic with two single nucleotide substitutions (449t/a and 527g/a) in evolutionarily conserved regions causing amino acid changes (F31I and V57I). Two other nucleotide substitutions (287c/g and 1891g/c) of unknown significance are in 5′ and 3′ untranslated regions (UTR), respectively. To learn more about the involvement of STK15 in ovarian cancer, we genotyped and haplotyped these polymorphisms in three population-based ovarian cancer case-control studies from the United Kingdom, United States, and Denmark with 1,821 combined cases and 2,467 combined controls and calculated risks for developing ovarian cancer. Genotypes of individual polymorphisms in control groups of the United Kingdom, United States, and Denmark conformed to Hardy-Weinberg equilibrium. In combined cases and combined controls, rare allele frequencies were 0.23 and 0.21 for I31, 0.16 and 0.17 for I57, 0.08 and 0.07 for 5′ UTR g, and 0.25 and 0.24 for 3′ UTR c, respectively. Using FF common homozygotes of F31I as comparator, there was increased ovarian cancer risk to FI heterozygotes (odds ratio, 1.18; 95% confidence interval, 1.01-1.36), II homozygotes (odds ratio, 1.25; 95% confidence interval, 0.89-1.75), and I31 allele carriers (odds ratio, 1.17; 95% confidence interval, 1.02-1.35) in the combined group data. For either V57I, 5′ UTR C/G, or 3′ UTR G/C, all genotypic ovarian cancer risks were essentially in unity relative to their respective common homozygotes, VV, cc, or gg. Haplotype analysis of combined group data revealed seven haplotypes with frequencies between 0.02 and 0.5, with c-F-V-g the most common. None of the haplotype-specific risks significantly differed from unity relative to c-F-V-g. These results suggest a model of dominant inheritance of ovarian cancer risk by the I31 allele of F31I and that the I31 allele may be a common ovarian cancer susceptibility allele of low penetrance.
A Comparison of Urinary Biomarkers of Tobacco and Carcinogen Exposure in Smokers
Authors: Murphy Sharon E. , Link Carrie A. , Jensen Joni , Le Chap , Puumala Susan S. , Hecht Stephen S. , Carmella Steven G. , Losey London , Hatsukami Dorothy K.
Published: June 2022

Recently, several potential harm reduction strategies, such as reduction in the number of cigarettes smoked and the use of modified cigarette products, have been discussed as possible means by which to reduce tobacco-related disease. To assess any potential reduction in harm by either of these approaches requires an accurate assessment of tobacco toxin exposure. We have recently completed a cigarette reduction study in which smokers were required to reduce the number of cigarettes smoked by 75%. This reduction took place over a 6-week period. We report here the comparison of urinary concentrations of tobacco alkaloid and tobacco carcinogen biomarkers in a subset of these same smokers during a 7-week period prior to any reduction in cigarette consumption. Urine samples were collected at four time points and analyzed for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), and its glucuronide, 1-hydroxypyrene, anatabine, free nicotine, total nicotine (free plus glucuronidated), free cotinine, total cotinine (free plus glucuronidated), and total trans-3′-hydroxycotinine (free plus glucuronidated). Anatabine is a minor alkaloid that may be useful in assessing tobacco exposure in individuals using nicotine replacement therapies. Urinary anatabine levels were well correlated (P < 0.0001) with both free and total nicotine (r = 0.753 and 0.773, respectively). Anatabine levels were also correlated with free cotinine (r = 0.465; P < 0.001), total cotinine (r = 0.514; P < 0.001), and total NNAL (r = 0.633; P < 0.001). These data support the role of anatabine as a biomarker of tobacco exposure. 1-Hydroxypyrene is a biomarker of polycyclic aromatic hydrocarbon exposure, but unlike NNAL it is not tobacco specific. Whereas urinary concentrations of 1-hydroxypyrene were consistent across the four visits, the levels were not correlated with NNAL, anatabine, nicotine, or any nicotine metabolites.
Effects of Genetic Polymorphisms of Metabolic Enzymes on Cytokinesis-Block Micronucleus in Peripheral Blood Lymphocyte among Coke-Oven Workers
Authors: Leng Shuguang , Dai Yufei , Niu Yong , Pan Zufei , Li Xiaohua , Cheng Juan , He Fengsheng , Zheng Yuxin
Published: June 2022

Exploring the associations between genetic polymorphisms of metabolic enzymes and susceptibility to polycyclic aromatic hydrocarbon (PAH)–induced chromosomal damage is of great significance for understanding PAH carcinogenesis. Cytochrome P450, glutathione S-transferase, microsomal epoxide hydrolase, NAD(P)H:quinone oxidoreductase, and N-acetyltransferase are PAH-metabolizing enzymes. In this study, we genotyped for the polymorphisms of these genes and assessed their effects on cytokinesis-block micronucleus (CBMN) frequencies in peripheral blood lymphocytes among 141 coke-oven workers and 66 non–coke-oven worker controls. The geometric means of urinary 1-hydroxypyrene levels in coke-oven workers and the controls were 12.0 and 0.7 μmol/mol creatinine, respectively (P < 0.01). The CBMN frequency (number of micronuclei per 1,000 binucleated lymphocytes) was significantly higher in coke-oven workers (9.5 ± 6.6‰) than in the controls (4.0 ± 3.6‰; P < 0.01). Among the coke-oven workers, age was positively associated with CBMN frequency; the mEH His113 variant genotype exhibited significantly lower CBMN frequency (8.5 ± 6.5‰) than did the Tyr113/Tyr113 genotype (11.3 ± 6.4‰; P < 0.01); the low mEH activity phenotype exhibited a lower CBMN frequency (8.6 ± 6.8‰) than did the high mEH activity phenotype (13.2 ± 6.7‰; P = 0.01); the GSTP1 Val105/Val105 genotype exhibited a higher CBMN frequency (15.0 ± 5.8‰) than did the GSTP1 Ile105/Ile105 or Ile105/Val105 genotypes (9.3 ± 6.5‰; P < 0.01); the joint effect of high mEH activity phenotype and GSTM1 null genotype on CBMN frequencies was also found. Gene-environment interactions between occupational PAH exposure and polymorphisms of mEH and/or GSTM1 were also evident. These results indicate that the mEH, GSTP1, and GSTM1 polymorphisms may play a role in sensitivity or genetic susceptibility to the genotoxic effects of PAH exposure in the coke-oven workers.
Metabolic Syndrome and the Risk of Prostate Cancer in Finnish Men: A Population-Based Study
Authors: Laukkanen Jari A. , Laaksonen David E. , Niskanen Leo , Pukkala Eero , Hakkarainen Anna , Salonen Jukka T.
Published: June 2022

Objective: Individual components of metabolic syndrome have been linked to an increased risk for prostate cancers. We hypothesized that metabolic syndrome itself could confer an increased risk for incident prostate cancer. Methods: The participants were a population-based sample of 1,880 men from eastern Finland without history of cancer or diabetes mellitus at baseline. Results: The metabolic syndrome (WHO criteria) was present in 357 (19%) of subjects. During an average follow-up of 13 years, a total of 183 cancers occurred, of which 56 were due to prostate cancer. The metabolic syndrome at baseline was related to a 1.9-fold (95% confidence interval, 1.1-3.5) risk of prostate cancer after adjustment for age, alcohol consumption, physical fitness, and energy, fat, fiber, calcium, vitamin E, and α-linolenic acid intake. The association between metabolic syndrome and risk of prostate cancer was stronger among overweight and obese men with a body mass index ≥27 kg/m2 (adjusted relative risk, 3.0; 95% confidence interval, 1.2-7.3) than in lighter men (relative risk, 1.8; 95% confidence interval, 0.7-4.7). Conclusions: Middle-aged men with the metabolic syndrome were more likely to develop prostate cancer in this prospective population-based study. This finding suggests that efforts to curb the epidemic of overweight and sedentary lifestyle and the accompanying metabolic syndrome may decrease the risk for prostate cancer.
Robustness of Case-Control Studies of Genetic Factors to Population Stratification: Magnitude of Bias and Type I Error
Authors: Khlat Myriam , Cazes Marie-Hélène , Génin Emmanuelle , Guiguet Marguerite
Published: June 2022

Case-control studies of genetic factors are prone to a special form of confounding called population stratification, whenever the existence of one or more subpopulations may lead to a false association, be it positive or negative. We quantify both the bias (in terms of confounding risk ratio) and the probability of false association (type I error) in the most unfavorable situation in which only one high-risk subpopulation is hidden within the studied population, considering different scenarios of population structuring and varying sample sizes. In accord with previous work, we find that the bias is likely to be small in most cases. In addition, we show that the same applies to the associated type I error whenever the subpopulation is small in proportion. For instance, when the hidden subpopulation makes up 5% of the entire population, with an allelic frequency of 0.25 (versus 0.10) and a disease rate that is double, then the estimated bias is 1.07 and the type I error associated with a sample of 500 cases and 500 controls is 8% (instead of 5%). We also show that the type I error is substantially greater for a rare allele (frequency of 0.1) than for a common allele (frequency of 0.5) and analyze the pattern of increase of vulnerability to stratification bias with sample size. Based on our findings, we may therefore conclude that with moderate sample sizes the type I error associated with population stratification remains very limited in most realistic scenarios.