bluuebunny/crossref_metadata_2025 huggingface dataset:
Amount, Type, and Timing of Recreational Physical Activity in Relation to Colon and Rectal Cancer in Older Adults: the Cancer Prevention Study II Nutrition Cohort
Authors: Chao Ann , Connell Cari J. , Jacobs Eric J. , McCullough Marjorie L. , Patel Alpa V. , Calle Eugenia E. , Cokkinides Vilma E. , Thun Michael J.
Published: June 2022

Physical activity has consistently been associated with lower risk of colon cancer, but information is limited on the amount, type, and timing of activities. The relationship between physical activity and rectal cancer is unclear. We examined characteristics of recreational physical activity in relation to colon and rectal cancer in the Cancer Prevention Study II Nutrition Cohort of 70,403 men and 80,771 women (median age, 63 years); 940 colon and 390 rectal cancers were identified from enrollment in 1992 to 1993 through August 1999. The multivariate-adjusted rate ratios (95% confidence intervals) associated with any recreational physical activity compared with none were 0.87 (0.71-1.06) for colon cancer and 0.70 (0.53-0.93) for rectal cancer. Colon cancer risk decreased significantly with increasing total hours (P for trend without reference group = 0.007) and metabolic equivalent hours (P for trend = 0.006) per week of activities. No clear decrease in rectal cancer risk was seen with increasing hours per week of physical activity. Rate ratios (95% confidence intervals) were 0.72 (0.52-0.98) for <2 hours, 0.68 (0.47-0.97) for 2 to 3 hours, 0.59 (0.41-0.83) for 4 to 6 hours, and 0.83 (0.59-1.16) for ≥7 hours per week of physical activity compared with none. Past exercise, as reported in 1982, was not associated with risk of either colon or rectal cancer. We conclude that increasing amounts of time spent at recreational physical activity are associated with substantially lower risk of colon cancer and that recreational physical activity is associated with lower risk of rectal cancer in older men and women.
Physical Activity in Relation to All-Site and Lung Cancer Incidence and Mortality in Current and Former Smokers
Authors: Alfano Catherine M. , Klesges Robert C. , Murray David M. , Bowen Deborah J. , McTiernan Anne , Vander Weg Mark W. , Robinson Leslie A. , Cartmel Brenda , Thornquist Mark D. , Barnett Matt , Goodman Gary E. , Omenn Gilbert S.
Published: June 2022

Increased physical activity has been associated with a reduction in the incidence and mortality from all-site cancer and some site-specific cancers in samples of primarily nonsmoking individuals; however, little is known about whether physical activity is associated with similar risk reductions among smokers and ex-smokers. This study examined physical activity in relation to all-site cancer and lung cancer incidence and mortality in a sample of current and former smokers (n = 7,045; 59% male; 95% Caucasian; mean age, 63 years) drawn from the β-Carotene and Retinol Efficacy Trial, a lung cancer chemoprevention trial. Hazard rate ratios and 95% confidence intervals associated with a 1 SD increase in physical activity were 0.86 (0.80-0.94) for all-site cancer only among men, 0.84 (0.69-1.03) for lung cancer only for younger participants, 0.75 (0.59-0.94) for cancer mortality among younger participants and 0.68 (0.53-0.89) among women, and 0.69 (0.53-0.90) for lung cancer mortality only among women. These results suggest that incidence may be more attenuated by physical activity for men and mortality more attenuated for women. Effects may be more pronounced for younger people and may differ inconsistently by pack-years of smoking. Physical activity may play a role in reducing cancer risk and mortality among those with significant tobacco exposure. Prospective studies using more sophisticated measures of physical activity assessed at multiple time points during follow-up are needed to corroborate these associations.
Variants of the IL8 and IL8RB Genes and Risk for Gastric Cardia Adenocarcinoma and Esophageal Squamous Cell Carcinoma
Authors: Savage Sharon A. , Abnet Christian C. , Mark Steven D. , Qiao You-Lin , Dong Zhi-Wei , Dawsey Sanford M. , Taylor Philip R. , Chanock Stephen J.
Published: June 2022

The population of Linxian in north central China is at high risk for gastric cardia adenocarcinoma (GCC) and esophageal squamous cell carcinoma (ESCC), and chronic inflammation may contribute to this risk. Interleukin-8 (IL8), a potent chemoattractant, has three well-characterized single nucleotide polymorphisms (SNP), one (−251) of which alters transcriptional activity. Four well-described SNPs in the two IL8 receptors, IL8RA and IL8RB, have been associated with inflammation. We conducted a case-cohort study in the Nutrition Intervention Trials (Linxian, China) to assess the association between these SNPs and incident GCC (n = 90) and ESCC (n = 131). IL8, IL8RA, and IL8RB SNPs were analyzed using a multiplex assay system, haplotypes were constructed, and risks were estimated using Cox proportional hazards models. The homozygous variants of IL8 −251 and +396 were associated with 2-fold increased relative risks for GCC, but the highest risk observed was for the AGT/AGC haplotype of IL8 −251/+396/+781 (relative risk, 4.14; 95% confidence interval, 1.31-13.1). Variation within IL8 was not associated with ESCC. Few subjects had variation at the IL8RA SNP and no significant associations were observed for IL8RB SNPs or haplotypes with either GCC or ESCC. We conclude that variation in IL8 seems to increase the risk for GCC but not ESCC in this high-risk population. These variants could confer an altered IL8 expression pattern or interact with environmental factors to increase the risk for inflammation and GCC.
Uptake of Offer to Receive Genetic Information about BRCA1 and BRCA2 Mutations in an Australian Population-Based Study
Authors: Keogh Louise A. , Southey Melissa C. , Maskiell Judi , Young Mary-Anne , Gaff Clara L. , Kirk Judy , Tucker Katherine M. , Rosenthal Doreen , McCredie Margaret R.E. , Giles Graham G. , Hopper John L.
Published: June 2022

Research on the utilization of genetic testing services for mutations in BRCA1 and BRCA2 has focused on women with a strong family history of breast and ovarian cancer. We conducted a population-based case-control-family study of Australian women diagnosed with invasive breast cancer before age 40 years, unselected for family history, and tested for germ line mutations in BRCA1 and BRCA2. Case subjects found to carry a deleterious mutation and their relatives who had given a research blood sample were informed by mail that the study had identified “genetic information” and were offered the opportunity to learn more. Those interested were referred to a government-funded family cancer clinic. Of 94 subjects who received the letter, 3 (3%) did not respond and 38 (40%) declined to learn their result (16 declined the referral, 10 accepted but did not attend a clinic, and 12 attended a clinic but declined testing), and 12 (13%) remain “on hold.” The remaining 41 (44%) chose to learn their result (3 of whom already knew their mutation status). There was no evidence that the decision to learn of mutation status depended on age, gender, family history, or having been diagnosed with breast cancer. Of 19 families with more than one participant, in 11 (58%) there was discordance between relatives in receiving genetic results. Although in Australia genetic testing is offered free of charge and insurance issues are not a major consideration, we found considerable reluctance, indecision, and unexplained variability both between and within case families in the desire to know their mutation status.
Aspirin and Other Nonsteroidal Anti-inflammatory Drugs and Breast Cancer Incidence in a Large U.S. Cohort
Authors: Jacobs Eric J. , Thun Michael J. , Connell Cari J. , Rodriguez Carmen , Henley S. Jane , Feigelson Heather S. , Patel Alpa V. , Flanders W. Dana , Calle Eugenia E.
Published: June 2022

Use of nonsteroidal anti-inflammatory drugs (NSAIDs), particularly aspirin, has consistently been associated with reduced risk of breast cancer in case-control studies. However, results from prospective studies have been less consistent. We examined the association between NSAID use and breast cancer incidence, adjusting for multiple breast cancer risk factors among 77,413 women in the Cancer Prevention Study II Nutrition Cohort. During follow-up from 1992 to 2001, we observed 3,008 cases of incident breast cancer. Information on NSAID use was obtained from a questionnaire completed at enrollment in 1992 or 1993 and was updated using follow-up questionnaires in 1997 and 1999. NSAID use was modeled using time-dependent variables to update exposure status. Neither current total NSAID use (aspirin and other NSAIDs combined) nor current aspirin use were associated with breast cancer incidence even at relatively high levels of use [rate ratio (RR), 1.07; 95% confidence interval (95% CI), 0.96-1.21 for ≥60 NSAID pills per month compared with no reported use of NSAIDs; RR, 1.01; 95% CI, 0.84-1.20 for ≥60 aspirin per month compared with no reported use of aspirin]. Even long-duration regular use (≥30 pills per month for ≥5 years) was not associated with breast cancer incidence (RR, 1.05; 95% CI, 0.88-1.26 for total NSAIDs; RR, 0.88; 95% CI, 0.69-1.12 for aspirin). Although we cannot exclude a small reduction in breast cancer risk associated with NSAID use, the results of this study provide evidence against a large reduction in risk.
Physical Activity in Different Periods of Life and the Risk of Breast Cancer: The Norwegian-Swedish Women's Lifestyle and Health Cohort Study
Authors: Margolis Karen L. , Mucci Lorelei , Braaten Tonje , Kumle Merethe , Trolle Lagerros Ylva , Adami Hans-Olov , Lund Eiliv , Weiderpass Elisabete
Published: June 2022

Background: Physical activity has been found to be associated with decreased risk of breast cancer in postmenopausal women in the majority of epidemiologic studies, but the association is inconsistent in premenopausal women.

Methods: We studied the effect of physical activity at various ages on the incidence of breast cancer in 99,504 women from 30 to 49 years of age at enrollment in the Women's Lifestyle and Health Study, a prospective population-based cohort study in Norway and Sweden. Physical activity level on an ordinal scale at age 14, age 30, and age at enrollment, participation in competitive sports, as well as information on other covariates was obtained using a self-administered questionnaire. Complete follow-up with data on incident invasive breast cancer and mortality was collected by linkage to national registries. The relation between physical activity and time to breast cancer development was assessed using Cox proportional hazard models, controlling for potential confounders.

Results: During an average 9.1 years of follow-up, there were 1,166 incident breast cancer cases. The mean age of the women was 41 years at enrollment, and the mean age at breast cancer diagnosis was 48 years. Compared to inactive women, women with higher levels of physical activity at enrollment had a similar risk of incident breast cancer (adjusted relative risk, 1.24 for vigorous activity compared with no activity; 95% CI, 0.85-1.82). Physical activity at age 30 or at age 14 also did not afford any significant protection from breast cancer, nor did a consistently high level of activity from younger ages to enrollment.

Conclusions: We did not find evidence of a protective effect of physical activity on breast cancer risk in this group of primarily premenopausal women.
The Role of Tomato Products and Lycopene in the Prevention of Prostate Cancer: A Meta-Analysis of Observational Studies
Authors: Etminan Mahyar , Takkouche Bahi , Caamaño-Isorna Francisco
Published: June 2022

Purpose: To determine whether intake of tomato products reduces the risk of prostate cancer using a meta-analysis. Methods: We systematically searched MEDLINE and EMBASE and contacted authors to identify potential studies. Log relative risks (RRs) were weighed by the inverse of their variances to obtain a pooled estimate with its 95% confidence interval (CI). Logistic regression and Poisson regression analyses were used to determine the effect produced by a daily intake of one serving of tomato product. Results: Eleven case-control studies and 10 cohort studies or nested case-control studies presented data on the use of tomato, tomato products, or lycopene and met our inclusion criteria. Compared with nonfrequent users of tomato products (1st quartile of intake), the RR of prostate cancer among consumers of high amounts of raw tomato (5th quintile of intake) was 0.89 (95% CI 0.80–1.00). For high intake of cooked tomato products, this RR was 0.81 (95% CI 0.71–0.92). The RR of prostate cancer related to an intake of one serving/day of raw tomato (200 g) was 0.97 (95% CI 0.85–1.10) for the case-control studies and 0.78 (95% CI 0.66–0.92) for cohort studies. Conclusion: Our results show that tomato products may play a role in the prevention of prostate cancer. However, this effect is modest and restricted to high amounts of tomato intake. Further research is needed to determine the type and quantity of tomato products with respect to their role in preventing prostate cancer.
Decreased Retinoid X Receptor-α Protein Expression in Basal Cells Occurs in the Early Stage of Human Prostate Cancer Development
Authors: Mao Gloria E. , Reuter Victor E. , Cordon-Cardo Carlos , Dalbagni Guido , Scher Howard I. , deKernion Jean B. , Zhang Zuo-Feng , Rao Jianyu
Published: June 2022

The development of prostatic intraepithelial neoplasia (PIN)-like lesions in the prostate-specific retinoid X receptor-α (RXRα) null mouse suggests that RXRα may protect against neoplasia. The purpose of this study was to characterize RXRα protein expression in human prostate to determine if RXRα is altered in early stages of tumor progression. Immunohistochemistry with anti-RXRα antibody was performed on 138 fresh frozen prostate specimens collected from 27 noncarcinomatous prostates and 111 radical prostatectomy samples of prostate adenocarcinoma (CA). The RXRα signal intensity was scored using a scale of 0–3. In normal glands, RXRα was expressed strongly in basal cells and only weakly in secretory epithelial cells. This finding was confirmed by double immunofluorescence labeling of RXRα and Keratin-903, a basal cell marker, followed by confocal microscopic examination. In basal cells, a gradual decrease of RXRα expression was noted from normal glands of noncarcinomatous prostate (3.0 ± 0) to “normal” glands distant to CA (2.13 ± 0.44) to “normal” glands adjacent to CA (1.25 ± 0.53) and high-grade PIN (0.56 ± 0.58). While nearly all “normal” glands from 138 specimens were positive for RXRα in basal cells, only 48% (13 of 27) of the high-grade PIN glands appeared positive. Moreover, basal cell expression of RXRα in “normal” tissue was less in specimens with poorly differentiated tumor (Gleason score ≥ 8; 1.83 ± 0.36) compared with well-differentiated tumor (Gleason score < 6; 2.35 ± 0.34; P = 0.04). Thus, a decrease of RXRα in the basal cells may serve as a marker for prostate CA-associated field change, which may represent an early event in the prostate carcinogenic process. These findings suggest that chemoprevention strategies with retinoids may be most effective if applied during the early stages of transformation.
Insulin-Like Growth Factors, Insulin-Like Growth Factor-Binding Proteins, and Endometrial Cancer in Postmenopausal Women: Results from a U.S. Case-Control Study
Authors: Lacey James V. , Potischman Nancy , Madigan M. Patricia , Berman Michael L. , Mortel Rodrigue , Twiggs Leo B. , Barrett Rolland J. , Wilbanks George D. , Lurain John R. , Fillmore Capri-Mara , Sherman Mark E. , Brinton Louise A.
Published: June 2022

Objective: To assess whether circulating insulin-like growth factor-1 (IGF-1), IGF-2, insulin-like growth factor-binding protein-1 (IGFBP-1), or IGFBP-3 were associated with endometrial cancer in postmenopausal women. Study Design: Between 1987 and 1990, we conducted a case-control study of 405 women with endometrial cancer and 297 matched population-based controls. This analysis included 174 postmenopausal cases and 136 controls. Results: In logistic regression models adjusted for potential confounders, higher IGF-1 levels were not positively associated with endometrial cancer: odds ratio (OR) for the highest tertile versus the lowest tertile = 0.63, 95% confidence interval (CI) = 0.30–1.32. Endometrial cancer was inversely associated with IGF-2 (OR for the highest tertile = 0.35, 95% CI = 0.18–0.69) and IGFBP-3 (OR for the highest tertile = 0.40, 95% CI = 0.21–0.77), and not associated with IGFBP-1. Conclusion: Serum IGF-1, IGF-2, and IGFBP-3, but not IGFBP-1, were inversely associated with endometrial cancer in postmenopausal women. These associations and the potential role of the IGF system in endometrial proliferation and carcinogenesis warrant further research.
Colorectal Cancer Screening Adherence in a General Population
Authors: Yeazel Mark W. , Church Timothy R. , Jones Resa M. , Kochevar Laura K. , Watt Gavin D. , Cordes Jill E. , Engelhard Deborah , Mongin Steven J.
Published: June 2022

Background: This article describes the self-reported colorectal cancer (CRC) screening adherence rates of adults, aged 50 years and older, living in five nonurban Minnesota counties. Methods: During the year 2000, 1693 eligible respondents, aged 50 years and older, from a randomly selected sample completed a survey assessing CRC screening adherence (∼86.3% response). The survey allowed differentiation between the four CRC screening modalities but did not differentiate between screening and diagnostic testing. Adjustment for nonresponse was performed using a version of Horvitz-Thompson weighting accounting for unknown eligibility. Results: 24.5% of respondents had a fecal occult blood test within 1 year of the survey, 33.8% had flexible sigmoidoscopy within 5 years, 29.3% had a colonoscopy within 10 years, and 13.7% had a barium enema within the last 5 years. Overall, 55.3% of respondents reported testing by any modality; thus, 44.7% were not adherent to screening guidelines. Conclusions: This study improves on previous attempts to characterize CRC screening adherence by assessing all four modalities of screening as recommended by current screening guidelines, by focusing on nonadherence, and by rigorously accounting for nonresponse. This study confirms that nearly half of the population remains unscreened by any method.
Loss of Antigenicity in Stored Sections of Breast Cancer Tissue Microarrays
Authors: Fergenbaum Jennifer H. , Garcia-Closas Montserrat , Hewitt Stephen M. , Lissowska Jolanta , Sakoda Lori C. , Sherman Mark E.
Published: June 2022

Immunohistochemical characterization of tumor tissues in epidemiological studies is a promising approach to identify breast cancer subtypes with distinct etiology. The recent development of the tissue microarray (TMA) technique allows for standardized, rapid, and cost-effective immunohistochemical characterization of many cases, which is critical in epidemiological studies. Sectioning paraffin blocks at different times results in loss of material, which can be reduced by preparing many sections each time a block is cut. However, data suggest that staining intensity declines in whole sections prepared from conventional paraffin blocks with storage time, resulting in false-negative results. This problem would be accentuated in TMAs because of the limited tissue representation of each case. To evaluate this concern, we prepared a single TMA block from 125 invasive breast carcinomas collected in a population-based case-control study conducted in Poland and compared estrogen receptor (ER-α), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression in sections cut and stored for 6 months at room temperature with sections cut from the same TMA block and stained on the same day. Percentage of positive cases for stored versus fresh sections was similar for ER (59.0%) but significantly higher in fresh sections for PR (56.3% versus 64.1%, P = 0.01) and HER2 (45.5% versus 64.4%, P < 0.001). Among cases positive in both stored and fresh sections, the median percentage of immunoreactive cells was significantly reduced and the staining intensity was consistently lower in stored compared with fresh sections. We conclude that loss of immunoreactivity is an important problem in TMAs of breast cancer. Improved methods for sectioning TMAs and storing tissue sections aimed at reducing loss of immunoreactivity are critical for the use of TMAs in epidemiological studies.
Population-Based Case-Control Study of CYP11A Gene Polymorphism and Breast Cancer Risk
Authors: Zheng Wei , Gao Yu-Tang , Shu Xiao-Ou , Wen Wanqing , Cai Qiuyin , Dai Qi , Smith Jeffrey R.
Published: June 2022

The CYP11A gene encodes the cholesterol side-chain cleavage enzyme (P450scc) that catalyzes the first and rate-limiting step for the biosynthesis of sex hormones. A pentanucleotide repeat [(TAAAA)n] polymorphism in the 5′ of the CYP11A gene has been reported to be related to the risk of polycystic ovary syndrome, an inherited endocrine disorder characterized by hyperandrogenemia. We investigated the association of this polymorphism with breast cancer risk in a population-based case-control study conducted among Chinese women in Shanghai. Genotype assays were completed for 1015 incident breast cancer cases and 1082 community controls. Three common alleles with 4, 6, or 8 TAAAA repeats were identified in the study population. The frequency of the 8 repeat allele was more common in cases (12.6%) than controls (8.5%) (odds ratio = 1.6, 95% confidence interval = 1.3–1.9; P < 0.0001). Compared to subjects who did not carry this allele, adjusted odds ratios were 1.5 (95% confidence interval = 1.2–1.9) and 2.9 (1.3–6.7) (P for trend, <0.001), respectively, for those who carried one and two copies of this allele. This positive association was observed in both pre- and postmenopausal women and all strata defined by major breast cancer risk factors, including years of menstruation, body mass index, and waist-to-hip ratio. The results from this study indicate that the TAAAA repeat polymorphism near the promoter region of the CYP11A gene may be an important susceptibility factor for breast cancer risk.
Physical Activity and Risk of Ovarian Cancer: A Prospective Cohort Study in the United States
Authors: Hannan Lindsay M. , Leitzmann Michael F. , Lacey James V. , Colbert Lisa H. , Albanes Demetrius , Schatzkin Arthur , Schairer Catherine
Published: June 2022

Increased physical activity may lower the risk of ovarian cancer by reducing the frequency of ovulation, decreasing body fat, or diminishing chronic inflammation. Previous epidemiological studies examining the association between physical activity and risk of ovarian cancer have been inconsistent. We investigated the association of physical activity with ovarian cancer in a prospective cohort of 27,365 individuals from the Breast Cancer Detection Demonstration Project. During 227,045 person-years of follow-up, 121 cases of ovarian cancer were ascertained. Usual physical activity during the past year was assessed by a self-administered questionnaire. After adjusting for potential risk factors for ovarian cancer, the relative risks (95% confidence intervals) across increasing quintiles of total physical activity were 1.0, 0.73 (0.43–1.25), 0.84 (0.50–1.40), 0.56 (0.31–1.00), and 0.70 (0.41–1.21), respectively (P for trend = 0.13). In this prospective cohort study among U.S. women, we found no overall significant association between physical activity and risk of ovarian cancer, although the results are suggestive of an inverse association.
Urinary Excretion of Flavonoids Reflects Even Small Changes in the Dietary Intake of Fruits and Vegetables
Authors: Brevik Asgeir , Rasmussen Salka Elbøl , Drevon Christian A. , Andersen Lene Frost
Published: June 2022

Background: Due to the random and systematic measurement errors associated with current dietary assessment instruments, there is a need to develop more objective methods of measuring the intake of foods of importance to human health. Objective: The purpose of this study was to test whether urinary excretion of flavonoids could be used to identify subjects who are meeting Norwegian recommendations for fruit and vegetable intake (5 servings per day) from individuals who are consuming the national average amount of fruits and vegetables (2 servings per day). Design: Twenty-four-hour urine samples were collected in a strict crossover controlled feeding study. Forty healthy subjects (19–34 years) were included in the study. After a 1-week run-in period, one group was given a controlled diet that included 2 servings (300 g) of fruits and vegetables daily for 14 days, while the other group was given a diet containing 5 servings (750 g) per day. Following a 2-week washout and a 1 week run-in period, the regimens were switched between the groups. Results: An increased intake of mixed fruits and vegetables from 2 to 5 servings per day significantly enhanced urinary excretion of eriodictyol, naringenin, hesperetin, quercetin, kaempferol, isorhamnetin, and tamarixetin. The citrus flavonoids naringenin and hesperetin showed a steep dose-response relationship to dietary intake of fruits and vegetables, whereas the association to eriodictyol, quercetin, kaempferol, isorhamnetin, and tamarixetin was more moderate. Conclusion: The present study indicates that urinary excretion of dietary flavonoids may be used to assess changes of mixed fruit and vegetable intake corresponding to an increase from the present national intake in Norway to the recommended amount of 5 servings of fruits and vegetables daily.
Influence of CYP1A1, GSTM1, GSTT1, and NQO1 Genotypes and Cumulative Smoking Dose on Lung Cancer Risk in a Swedish Population
Authors: Alexandrie Anna-Karin , Nyberg Fredrik , Warholm Margareta , Rannug Agneta
Published: June 2022

The major identified risk factor for lung cancer is tobacco smoking. We identified previously the possible modifying influence of CYP1A1 and GSTM1 polymorphisms on lung cancer risk in a Swedish population. The present study, extended by several study subjects and with analyses for polymorphisms in GSTT1 and NQO1, includes 524 lung cancer cases and 530 control subjects. No evidence for an influence of genetic polymorphisms in CYP1A1, GSTM1, GSTT1, and NQO1 on lung cancer risk overall was found. In smokers, there was, however, a suggestion that the variant CYP1A1 and NQO1 genotypes may confer an increased risk for squamous cell carcinoma. In ever smokers, the homozygously deleted GSTM1 (GSTM1*O/*O) genotype was significantly associated with increased risk of small cell carcinoma (adjusted odds ratio 2.72, 95% confidence interval 1.32-5.90). The risks noted for the variant CYP1A1 genotypes and the GSTM1*O/*O genotype seemed to be restricted to light smokers. The GSTT1*O/*O genotype also appeared to be a possible risk factor in light smokers, whereas, in heavy smokers, this genotype was associated with decreased risk for lung cancer overall (odds ratio 0.36, 95% confidence interval 0.13-0.99). Due to the multiple comparisons made, we cannot exclude the possibility that some of these associations may represent chance findings.
Epidemiology of Urinary Melatonin in Women and Its Relation to Other Hormones and Night Work
Authors: Schernhammer Eva S. , Rosner Bernard , Willett Walter C. , Laden Francine , Colditz Graham A. , Hankinson Susan E.
Published: June 2022

Objective: Light exposure during night work suppresses melatonin production, and night work has been associated with an increased cancer risk. There is little information, however, about the interrelationships of night work, urinary melatonin levels, and levels of plasma steroid hormones in women. Method: We examined the reproducibility of morning urinary measurements of 6-sulfatoxymelatonin over a 3-year period in 80 premenopausal women. We assessed correlations between average urinary melatonin and plasma steroid hormone levels and evaluated potential associations between night work and hormone levels, using current and long-term shift work information from two large, prospective cohorts, the Nurses' Health Study cohorts. Results: The intraclass correlation for creatinine-adjusted 6-sulfatoxymelatonin was 0.72 (95% confidence interval, 0.65, 0.82). We found significantly increased levels of estradiol after longer durations of night work (geometric mean levels of estradiol, 8.8 pg/mL for women who never worked night shifts versus 10.1 pg/mL for women who worked 15 or more years of night shifts; P for trend = 0.03). We observed a significant inverse association between increasing number of nights worked within the 2 weeks preceding urine collection and urinary melatonin levels (r = −0.30, P = 0.008), but no association of recent night work with estradiol (r = 0.10, P = 0.41). Conclusion: A single morning urinary melatonin measurement is a reasonable marker for long-term melatonin levels among premenopausal women. Women who work on rotating night shifts seem to experience changes in hormone levels that may be associated with the increased cancer risk observed among night-shift workers.
Manganese Superoxide Dismutase Polymorphism, Plasma Antioxidants, Cigarette Smoking, and Risk of Breast Cancer
Authors: Tamimi Rulla M. , Hankinson Susan E. , Spiegelman Donna , Colditz Graham A. , Hunter David J.
Published: June 2022

Oxidative stress may be involved in the development of breast cancer. Manganese superoxide dismutase (MnSOD) is one of the primary enzymes that directly scavenge potential harmful oxidizing species. A valine (Val) to alanine (Ala) substitution at amino acid 16, occurring in the mitochondrial targeting sequence of the MnSOD gene, has been associated with an increase in breast cancer risk. We conducted a nested case-control study within the Nurses' Health Study cohort to examine the role of this polymorphism and its interaction with environmental factors with breast cancer risk. MnSOD genotype data are available from 968 incident cases of breast cancer diagnosed after blood collection in 1989 and 1990, but before June 1, 1998 and 1,205 matched controls. Compared with women homozygous for the Val allele, women homozygous for the Ala allele were not at an increased risk of breast cancer (multivariate odds ratio, 0.96; 95% confidence interval, 0.74-1.24). We did not observe any significant interactions between MnSOD genotype with alcohol consumption, postmenopausal hormone use, plasma antioxidant levels, or dietary sources of antioxidants. We did observe evidence that the MnSOD Ala allele may modify the relation of cigarette smoking with breast cancer risk. A nonsignificant increased risk of breast cancer among current smokers was limited to women homozygous for the Ala alleles compared with Val/Val never smokers (multivariate odds ratio, 1.41; 95% confidence interval 0.77-2.60; P for interaction = 0.03). These data suggest that the Ala allele of MnSOD may modify breast cancer risk among current smokers, but is not an independent risk factor for breast cancer.
Early-Onset Colorectal Cancer: A Call for Greater Rigor in Epidemiologic Studies
Authors: Molmenti Christine Louise S. , Jacobs Elizabeth T. , Gupta Samir , Thomson Cynthia A.
Published: June 2022

The rates of early-onset colorectal cancer (EO-CRC) have been rising by 0.5% to 2.4% annually for three decades, accounting for an estimated 12% of all colorectal cancer diagnosed in the United States in 2020. Enhancing the rigor and comprehensiveness of the epidemiology in terms of the exposures and prognostic biomarkers is essential if we are to modify risk factors and underlying mechanisms, ultimately arresting this unduly trend. This commentary serves to describe the disease trend, postulate underlying risk factors and mechanisms driving disease incidence, and proposes a call to action for cancer epidemiologists to promote increased and timely opportunities to intervene on this trend.
DAXX, ATRX, and MSI in PanNET and Their Metastases: Correlation with Histopathological Data and Prognosis
Authors: Gisder Doreen Maria , Overheu Oliver , Keller Julia , Nöpel-Dünnebacke Stefanie , Uhl Waldemar , Reinacher-Schick Anke , Tannapfel Andrea , Tischoff Iris
Published: June 2022

Introduction: Studies on pancreatic neuroendocrine tumors (PanNETs) regarding loss of ATRX, DAXX, or frequency of microsatellite instability (MSI) show inconclusive results. So far, data on corresponding metastaseshave not been published. Methods: We performed immunohistochemistry (IHC) of ATRX, DAXX, MSH2, MSH6, MLH1, and PMS2 on 74 PanNETs and 19 metastases. ATRX- and DAXX-negative PanNETs were further sequenced for mutations. We used polymerase chain reaction for MSI on cases with IHC loss of MSH2, MSH6, MLH1, and PMS2. Results: Immunohistochemical loss of DAXX and ATRX was observed in 8/74 (11%) and 6/74 (8%) PanNETs. Loss of DAXX immunoreactivity was statistically associated with higher tumor grade and showed a tendency toward a decreased overall survival. Sequencing of DAXX- (7/11 [64%]) and ATRX-negative (5/11 [45%]) PanNETs revealed a mutation in 6/7 (86%) and 2/5 (40%). The specificity of immunohistochemical loss of DAXX and ATRX for mutation was 80% and 67%, respectively. The expression status of DAXX compared to primary tumor differs in 2/12 (17%) lymph node metastases. We further identified 3/74 (4%) tumors as MSI, associated with a poor prognosis. Discussion/Conclusion: Our study supports the hypothesis that a loss of DAXX immunoreactivity can identify a more aggressive subtype of PanNET with high confidence, while ATRX loss is a weaker indicator. Our results also strengthen the role of DAXX immunolabeling as a prognostic marker. We could show that ATRX might be less suitable as a surrogate for sequencing. Our results indicate that IHC of DAXX and ATRX may identify PanNET subtypes as targets for more aggressive therapy.
Effects of Selenium and/or N-Acetyl-Cysteine Supplementation on Nonthyroidal Illness Syndrome in Hemodialysis Patients: A Factorial Randomized Controlled Trial
Authors: Shahreki Elham , Kaykhaei Mahmoud Ali , Mosallanezhad Zahra , Adineh Zahra , Mokhtari Ali Mohammad , Mohammadi Mahdi , Hosseini Razieh , Bazi Aliyeh
Published: June 2022

Introduction: Nonthyroidal illness syndrome (NTIS) is common in hemodialysis patients (HPs). However, limited clinical trials have been conducted in this field. Therefore, the aim of this study was to investigate the effect of Se and/or N-acetyl-cysteine (NAC) on NTIS parameters in HPs. Methods: In this factorial randomized controlled trial, 68 HPs were divided into four groups: group A received placebo of Se and NAC, group B received 600 μg per day of NAC and placebo of Se, group C received 200 μg of Se per day and placebo of NAC and group D received 200 μg of selenium and 600 μg of NAC per day for 12 weeks. Blood samples were taken at baseline and after 12 weeks to assess free tri-iodothyronine (FT3), free thyroxine (FT4), thyroid stimulating hormone (TSH), and reverse T3 (rT3) concentrations. Results: Our finding demonstrated that rT3 levels were decreased in B, C, and D groups and increased nearly to baseline levels in the A group after 12 weeks, with a marked difference between the groups (p < 0.001) based on ANOVA. Although there were no significant differences in FT3 (p = 0.39), FT4 (p = 0.76), and TSH (p = 0.71) between the groups at the end of the trial. Conclusion: This trial showed that Se and/or NAC exert beneficial effects on rT3 levels in HPs. However, long-term clinical trials with a larger sample size using more appropriate biomarkers are recommended to evaluate the efficacy and safety of Se and/or NAC in HPs.
Upregulated miR-146a Expression in Peripheral Blood Relates to Th17 and Treg Imbalance in Elder Rheumatoid Arthritis Patients
Authors: Liu Menglan , Ren Tianli , Lin Zhi , Hua Minhui
Published: June 2022

Background: The expression level of microRNA-146a (miR-146a) increased in peripheral blood and synovialis tissue of rheumatoid arthritis (RA) patient, and it may play an important role in the pathological process of RA. We investigated its possibility as a diagnostic marker and the correlation with T helper 17 (Th17) and Treg cells in elder RA patients. Methods: Blood samples were collected from 38 active RA patients, 38 inactive RA patients, and 40 healthy controls. RNA expression levels of miR-146a were detected from the peripheral blood samples. The proportion of Th17 and Treg cells were analyzed, as well as their cell-specific transcription factor retinoic acid-related orphan receptor variant 2 (RORc) and forkhead box protein 3 (FOXP3). Furthermore, secretion of pre-inflammatory and anti-inflammatory factors was detected. Correlations between miR-146a and these factors were also analyzed. Results: Compared with healthy control, expression levels of miR-146a in inactive and active groups were significantly higher, with the highest level in active group. The expression of miR-146a and the RA severity, Th17 cell ratio, RORc expression, IL-17 level showed a significant positive correlation, while it showed a significantly negative correlation with Treg cell ration, FOXP3 expression, and TGF-β1 secretion. Conclusions: These results suggested that miR-146a may be used as a disease progression marker in the peripheral blood of elder RA patients.
Caffeine: Some of the Evidence behind Its Use and Abuse in the Preterm Infant
Authors: Chavez Laura , Bancalari Eduardo
Published: June 2022

Apnea of prematurity is a developmental disorder affecting most extremely preterm infants. The consequences of apnea of prematurity on neurodevelopment are not well established, but several reports suggest that apnea and hypoxemia episodes may be associated with worse neurological outcome. Caffeine is the only FDA-approved drug for the prevention and treatment of apnea of prematurity. Besides its clear effectiveness to reduce apnea, the use of caffeine appears to have a wide margin of safety and has been associated with possible beneficial effects on later neurodevelopmental outcome. At the same time, there are also many studies in experimental animals and some in preterm infants suggesting potential serious adverse effects from caffeine administration, especially when using higher doses. Because of these uncertainties, there is a wide variation in caffeine use across institutions. This review summarizes some of the available evidence on caffeine use in this population, its indications and best timing of initiation and discontinuation, appropriate dosing, and some of the possible adverse effects of caffeine administration. Because of the many gaps in knowledge, especially as it relates to efficacy and safety, we encourage further basic and clinical studies to provide stronger evidence, not only on its potential beneficial effects but also its side effects.
Determinantes de infecção nosocomial tardia neonatal: estudo de caso-controle no Ceará
Authors: Lima Carmen Sulinete Suliano da Costa , Rocha Hermano Alexandre Lima , Araújo David Augusto Batista Sá , Silva Cláudia
Published: June 2022

OBJETIVO Identificar os fatores determinantes para infecções relacionadas à assistência à saúde (IRAS) tardias em terapia intensiva neonatal e multirresistência bacteriana. MÉTODOS Estudo caso-controle em unidade de terapia intensiva neonatal do Estado do Ceará, entre janeiro de 2013 e dezembro de 2017. Considerado caso o recém-nascido notificado como IRAS tardia e, controle, aquele sem infecção. Variáveis com valor de p ≤ 0,05 em análise regressiva bivariada inicial foram incluídas em modelo logístico hierarquizado não condicional para análise multivariada. Valores de p menores que 0,01 foram considerados significativos. RESULTADOS Dos 1.132 participantes, 427 (37,7%) tiveram infecções tardias relacionadas a assistência à saúde, com 54 (12,6%) hemoculturas positivas e 14,9% dessas foram bactérias multirresistentes. Na análise bivariada observou-se efeito protetor do sexo feminino (OR = 0,71; IC95% 0,56–0,90) e recém-nascido ≥ 34 semanas (OR = 0,48; IC95% 0,30–0,75). Nos mais prematuros, as infecções tardias tiveram chance dezoito vezes maior em menores do que 30 semanas (OR = 18,61; IC95% 9,84–35,22); e nos menores de 1.500g, quatro vezes maior (OR = 4,18; IC95% 3,12–5,61). O uso de ventilação mecânica aumentou em mais de sete vezes a chance (OR = 7,14; IC95% 5,26–9,09); o mesmo aconteceu com o recurso da nutrição parenteral (OR = 5,88; IC95% 4,54–7,69), com o cateter venoso central (OR = 10,00; IC95% 6,66–16,66); o número de cateteres utilizado (OR = 3,93; IC95% 3,02–5,12); a realização de cirurgia (OR = 4,00; IC95% 2,27–7,14) e o tempo de internamento (OR = 1,06; IC95% 1,05–1,07). Permaneceram significativos após ajuste: prematuro menor do que 30 semanas (OR = 5,62; IC95% 1,83–17,28); uso de ventilação (OR = 1,84; IC95% 1,26–2,68); uso de cateter venoso central (OR = 2,48; IC95% 1,40–4,37) e tempo de internamento (OR = 1,06; IC95% 1,05–1,07). Dentre os óbitos, 41 (55,4%) foram associados às infecções tardias. CONCLUSÃO Melhores práticas devem ser adotadas no cuidado da prematuridade e o uso racional de procedimentos, para evitar infecções tardias relacionadas a assistência à saúde, óbitos preveníveis e riscos de multirresistência bacteriana e contaminação ambiental.
Longitudinal Study Reveals Long-Term Proinflammatory Proteomic Signature After Ischemic Stroke Across Subtypes
Authors: Stanne Tara M. , Angerfors Annelie , Andersson Björn , Brännmark Cecilia , Holmegaard Lukas , Jern Christina
Published: June 2022

Background:

Inflammation contributes both to the pathogenesis of stroke and the response to brain injury. We aimed to identify proteins reflecting the acute-phase response and proteins more likely to reflect proinflammatory processes present before stroke by broadly profiling inflammation-related plasma proteins in a longitudinal ischemic stroke study.

Methods:

Participants were from a Swedish ischemic stroke cohort (SAHLSIS [Sahlgrenska Academy Study on Ischemic Stroke], n=600 cases and n=600 controls). Plasma levels of 65 proteins including chemokines, interleukins, surface molecules, and immune receptors were measured once in controls and at 3× in cases: during the acute phase, after 3 months, and for a subgroup (n=223) at 7-year follow-up. Associations between proteins and ischemic stroke or subtype were investigated in multivariable binary regression models corrected for age, sex, vascular risk factors, and multiple testing.

Results:

In the acute phase, 48 proteins were significantly and independently associated with ischemic stroke (false discovery rate adjusted
P
<0.05). At 3-month follow-up, 51 proteins and at 7-year follow-up 50 proteins were associated with ischemic stroke. The majority of proteins were upregulated in cases compared with controls (n=34 at all time points) and the most upregulated were CXCL5 (CXC chemokine ligand 5) and OSM (oncostatin M). Generally, large artery and cardioembolic stroke had the highest protein levels. However, several interesting subtype-specific differences were also detected at each time point.

Conclusions:

We found inflammation-related proteins that were differentially regulated in ischemic stroke cases compared with controls only in the acute phase and others that remained elevated also at later time points. This latter group of proteins could reflect underlying pathophysiological processes of relevance. Future studies both in terms of disease risk and prognostication are warranted.
Commitment through Sacrifice: How Longer Ramadan Fasting Strengthens Religiosity and Political Islam
Authors: Aksoy Ozan , Gambetta Diego
Published: June 2022

Religions seem to defy the law-of-demand, which suggests that all else equal, an increase in the cost of an activity will induce individuals to decrease the resources they spend on that activity. Rather than weakening religious organizations, evidence shows that the sacrifices exacted by religious practices are positively associated with the success of those organizations. We present the first strong evidence that this association is neither spurious nor endogenous. We use a natural experiment that rests on a peculiar time-shifting feature of Ramadan that makes the fasting duration—our measure of sacrifice—vary not just by latitude but from year-to-year. We find that a half-hour increase in fasting time during the median Ramadan day increases the vote shares of Islamist political parties by 11 percent in Turkey’s parliamentary elections between 1973 and 2018, and results in one additional attendee per 1,000 inhabitants for voluntary Quran courses. We further investigate two mechanisms, screening and commitment, that could explain the effects we find. By testing their divergent implications, we infer that commitment is the mechanism triggered by sacrifice, which drives up the intensity of religious beliefs and participation that in turn bolster the success of religious organizations.
Youth Decision-Making and Crime: Influences of Stressful Conditions, Adverse Mental and Physical States, and Conventional Activities
Authors: Timmer Anastasiia , Antonaccio Olena , French Michael T. , Botchkovar Ekaterina V.
Published: June 2022

This study focuses on sources of youth decision-making and examines paths through which these factors may affect delinquent behavior. Using longitudinal Add Health data, we explore the mediating mechanisms linking several antecedents of decision-making, thoughtfully reflective decision-making (TRDM), and crime. We find that various adverse factors (i.e., family and school stressful conditions, depression, sleep problems) reduce the ability of adolescents to be thoughtful and reflective, which leads to higher levels of criminal behavior. By contrast, involvement in conventional activities (i.e., hobbies, religious activities) is found to foster TRDM, which reduces delinquency. Our study calls for an integration of perspectives in criminology, cognitive psychology, and neuroscience to better explain the relationship between decision-making and crime. Policy implications are discussed.
Deviant Identity and Offending: A Longitudinal Study of South Korean Youths
Authors: O SooHyun , Lee YongJei , Wilcox Pamela , Cullen Francis T.
Published: June 2022

This study examines deviant identity in relation to youth offending by combining items tapping both self-appraisal and reflected appraisal. In particular, using survey data from 3,446 Korean youth across five waves of the Korea Youth Panel Survey (KYPS), findings from group-based trajectory modeling (GBTM) present four distinct offending groups—a high-rate chronic group, stable non-offending group, adolescence-limited group, and declining group. Then, findings from the multinomial logit model reveal that deviant identity is a robust predictor of offending for subgroups of adolescents involved in offending at any level in comparison to stable non-offenders. Accordingly, this study supports the idea that deviant identity should be considered as a prominent predictor of a variety of types of youth offending.