bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of a 2-Year Randomized Soy Intervention on Sex Hormone Levels in Premenopausal Women
Authors: Maskarinec Gertraud , Franke Adrian A. , Williams Andrew E. , Hebshi Sandra , Oshiro Caryn , Murphy Suzanne , Stanczyk Frank Z. 
Published: June 2022

AbstractObjective: Several epidemiologic studies have described protective effects of soy consumption against breast cancer. The goal of this trial among premenopausal women was to examine the effect of soy foods on menstrual cycle length and circulating sex hormone levels.Methods: This 2-year dietary intervention randomized 220 healthy premenopausal women. The intervention group consumed two daily servings of soy foods containing ∼50 mg of isoflavones; the control group maintained their regular diet. Five blood samples (obtained in months 0, 3, 6, 12, and 24) were taken 5 days after ovulation as determined by an ovulation kit. The serum samples were analyzed for estrone, estradiol, sex hormone binding globulin, androstenedione, and progesterone by immunoassay.Results: At baseline, both groups had similar demographic, anthropometric, and nutritional characteristics. The dropout rates of 15.6% (17 of 109) in the intervention group and 12.6% (14 of 111) in the control group did not differ significantly. According to soy intake logs, 24-hour recalls, and urinary isoflavone excretion, the women closely adhered to the study regimen. Menstrual cycles became slightly shorter in both groups but did not differ by group. Mixed general linear models indicated no significant intervention effect on any of the serum hormones. However, androstenedione and progesterone decreased significantly over time in both groups.Conclusions: The results of this study suggest that the preventive effects of soy on breast cancer risk in premenopausal women may not be mediated by circulating sex hormone levels. Different mechanisms of actions or effects of exposure earlier in life are alternate hypotheses that require further investigation.
Serum Insulin-Like Growth Factors, Insulin-Like Growth Factor Binding Proteins, and Breast Cancer Risk in Postmenopausal Women
Authors: Grønbæk Henning , Flyvbjerg Allan , Mellemkjær Lene , Tjønneland Anne , Christensen Jane , Toft Sørensen Henrik , Overvad Kim 
Published: June 2022

Abstract
Background: Studies have shown a positive association between serum insulin-like growth factor (IGF)-I and breast cancer risk in premenopausal but not postmenopausal women. IGF-II and estrogen receptor (ER) status has never been investigated. We examined the association between IGF-I, IGF-II, IGF binding protein (IGFBP)-2, IGFBP-3, and IGFBP-3 protease activity and breast cancer risk in postmenopausal women, taking ER status of the breast cancer into consideration.
Methods: We conducted this case-cohort study within a Danish follow-up study based on 24,697 postmenopausal women. We identified 411 cases with breast cancer and a matched control group including 397 cohort members. We estimated breast cancer risk using Cox regression analysis with adjustment for known breast cancer risk factors.
Results: We observed no association for IGF-I but a positive association between levels of IGFBP-3 and breast cancer risk. Per 500 units higher levels of IGFBP-3, an incidence rate ratio [IRR; 95% confidence interval (95% CI)] of 1.14 (1.00-1.30) was estimated. For ER-positive breast cancer, the IRR (95% CI) was 1.18 (1.05-1.33). IGFBP-3 protease activity was not associated with breast cancer risk. Per 275 units higher levels of IGF-II, an IRR (95% CI) of 1.35 (1.10-1.66) was observed for ER-positive tumors, whereas IGFBP-2 was not associated with breast cancer risk. Adjustment for potential confounders did not change the risk estimate. There was no association between IGF-I, IGF-II, IGFBP-2, or IGFBP-3 and risk of ER-negative breast cancer.
Conclusion: Serum IGFBP-3 and IGF-II levels were positively associated with ER-positive breast cancer risk. This may suggest an important relationship among IGFs, IGFBPs, the ER system, and breast cancer development in postmenopausal women.
Body Mass Index and Risk of Leukemia in Older Women
Authors: Ross Julie A. , Parker Emily , Blair Cindy K. , Cerhan James R. , Folsom Aaron R. 
Published: June 2022

Abstract
Overweight [body mass index (BMI) 25.0-29.9 kg/m2] and obesity (BMI ≥30 kg/m2) are risk factors for several malignancies. The Iowa Women's Health Study was examined to determine whether increased BMI was associated with leukemia development. Over 40,000 Iowa women (ages 55-69 years) completed a self-administered lifestyle and health questionnaire in 1986 that included current height and weight. Two hundred women developed leukemia during the period 1986 to 2001 including 74 acute myelogenous leukemia (AML) and 88 chronic lymphocytic leukemia. The risk of AML was increased among women who reported being overweight or obese (relative risk, 1.9; 95% confidence interval, 1.0-3.4; relative risk, 2.4; 95% confidence interval, 1.3-4.5; Ptrend = 0.006) compared with women of normal weight. There was little evidence of a positive association for chronic lymphocytic leukemia (Ptrend = 0.6). Given the prevalence of overweight and obesity in the United States, the population attributable risk of AML due to obesity could approach 30%.
The Relative Risks of a Low-Nitrosamine Smokeless Tobacco Product Compared with Smoking Cigarettes: Estimates of a Panel of Experts
Authors: Levy David T. , Mumford Elizabeth A. , Cummings K. Michael , Gilpin Elizabeth A. , Giovino Gary , Hyland Andrew , Sweanor David , Warner Kenneth E. 
Published: June 2022

AbstractA nine-membered panel of experts was asked to determine expert opinions of mortality risks associated with use of low-nitrosamine smokeless tobacco (LN-SLT) marketed for oral use. A modified Delphi approach was employed. For total mortality, the estimated median relative risks for individual users of LN-SLT were 9% and 5% of the risk associated with smoking for those ages 35 to 49 and ≥50 years, respectively. Median mortality risks relative to smoking were estimated to be 2% to 3% for lung cancer, 10% for heart disease, and 15% to 30% for oral cancer. Although individual estimates often varied between 0% and 50%, most panel members were confident or very confident of their estimates by the last round of consultation. In comparison with smoking, experts perceive at least a 90% reduction in the relative risk of LN-SLT use. The risks of using LN-SLT products therefore should not be portrayed as comparable with those of smoking cigarettes as has been the practice of some governmental and public health authorities in the past. Importantly, the overall public health impact of LN-SLT will reflect use patterns, its marketing, and governmental regulation of tobacco products.
MTHFR Polymorphisms, Diet, HRT, and Breast Cancer Risk: The Multiethnic Cohort Study
Authors: Le Marchand Loïc , Haiman Christopher A. , Wilkens Lynne R. , Kolonel Laurence N. , Henderson Brian E. 
Published: June 2022

Abstract
Methylenetetrahydrofolate reductase (MTHFR) is a key regulatory enzyme in the metabolism of folate, a nutrient which has recently been found to be inversely related to breast cancer in women who drink alcohol. Two common variants in the MTHFR gene (C677T and A1298C) have been associated with a reduced activity of this enzyme, thereby increasing the availability of folate for thymidylate and purine synthesis. We investigated the relationship of these variants with invasive breast cancer in a case-control study of 1,189 cases and 2,414 controls nested within the Multiethnic Cohort Study. The Multiethnic Cohort Study is a large prospective study of men and predominantly postmenopausal women of Japanese, White, African American, Latino, and Native Hawaiian origin, residing in Hawaii and Los Angeles. We found an overall nonsignificant, weak inverse association between breast cancer risk and the 677TT genotype and no association with the 1298C variant. The odds ratio [OR and 95% confidence interval (95% CI)] for the 677CC, 677CT, and 677TT genotypes were 1.00, 0.98 (0.83-1.15), and 0.86 (0.67-1.09), respectively. Those for the 1298AA, 1298AC, and 1298CC genotypes were 1.00, 0.93 (0.79-1.08), and 1.20 (0.88-1.65), respectively. However, the inverse association with the 677TT genotype was stronger (OR, 0.62; 95% CI 0.39-0.98) among women who were on hormone replacement therapy (HRT) at baseline, and the increased breast cancer risk due to HRT was not observed in women with the 677TT genotype. An increased breast cancer risk was suggested for alcohol intake &gt;10 g/d, when compared with nondrinkers, but only among HRT users with the 677CC genotype (OR, 1.51; 95% CI, 0.96-2.37). Folate intake exhibited no modifying effect on the genotype-breast cancer relationship. These findings suggest that the MTHFR 677TT genotype may confer a 40% decreased breast cancer risk in postmenopausal women using HRT. This is consistent with the role of MTHFR in facilitating the flow of folate for thymidylate and purine synthesis and with the increased nucleic acid need resulting from the hyperproliferative effect of HRT on mammary epithelial cells.
Mammographic Density and Estrogen Receptor Status of Breast Cancer
Authors: Ziv Elad , Tice Jeffrey , Smith-Bindman Rebecca , Shepherd John , Cummings Steven , Kerlikowske Karla 
Published: June 2022

Abstract
Background: The density of breast tissue on a mammogram is a strong predictor of breast cancer risk and may reflect cumulative estrogen effect on breast tissue. Endogenous and exogenous estrogen exposure increases the risk of estrogen receptor (ER)–positive breast cancer. We determined if mammographic density is associated more strongly with ER-positive breast cancer than with ER-negative breast cancer.
Methods: We analyzed data from 44,811 participants in the San Francisco Mammography Registry of whom 701 developed invasive breast cancer. Mammographic density was measured using the Breast Imaging Reporting and Data System (BI-RADS) classification system (1 = almost entirely fat, 2 = scattered fibroglandular, 3 = heterogeneously dense, 4 = extremely dense). We tested for associations between mammographic density and ER-positive and ER-negative breast cancer separately. Analyses were adjusted for age, body mass index, postmenopausal hormone use, family history of breast cancer, menopausal status, parity, and race/ethnicity.
Results: Mammographic density was strongly associated with both ER-positive and ER-negative breast cancers. Compared with women with BI-RADS 2, women with BI-RADS 1 (lowest density) had a lower risk of ER-positive cancer [adjusted hazard ratio (HR), 0.28; 95% confidence interval (95% CI), 0.16-0.50] and ER-negative cancer (adjusted HR, 0.17; 95% CI, 0.04-0.70). Women with BI-RADS 4 (highest density) had an increased risk of ER-positive breast cancer (adjusted HR, 2.21; 95% CI, 1.64-3.04) and an increased risk of ER-negative breast cancer (adjusted HR, 2.21; 95% CI, 1.16-4.18).
Conclusion: Surprisingly, women with high mammographic density have an increased risk of both ER-positive and ER-negative breast cancers. The association between mammographic density and breast cancer may be due to factors besides estrogen exposure.
Molecular Epidemiology of Physical Activity and Cancer
Authors: Rundle Andrew 
Published: June 2022

Abstract
As in other areas of epidemiology, researchers studying physical activity and cancer have begun to include laboratory analyses of biological specimens in their studies. The incorporation of these “biomarkers” into epidemiology has been termed molecular epidemiology and is an approach primarily developed to study chemical carcinogens. Thus far, there has been no discussion in the field on how the established molecular epidemiologic framework might be adapted for research into physical activity, what methodologic needs exist, what the goals of such an approach might be, and what limitations exist. This article relates the literature on molecular epidemiology to the needs of physical activity research and tries to set research priorities for the field as it moves in this new direction. Although this approach will be very useful for investigating the mechanisms through which physical activity exerts effects, there are several challenges for physical activity epidemiologists in adapting molecular epidemiologic approaches. Primarily, there are currently no available biomarkers that might be considered measures of exposure or biologically effective dose. In addition, most available biomarkers of intermediate effects have been tested in training studies at activity levels much higher than those seen in population-based epidemiologic studies. Thus, it is not clear whether these biomarkers are valid at lower activity levels. Furthermore, the nature of the relationship between activity and many available biomarkers depends very much on the context of the activity. Addressing these issues should be a priority if we are to develop a molecular epidemiologic paradigm for studying physical activity.
Population-Based Prevalence and Age Distribution of Human Papillomavirus Among Women in Santiago, Chile
Authors: Ferreccio Catterina , Prado Rodrigo B. , Luzoro Amaranta V. , Ampuero Sandra Ll. , Snijders Peter J.F. , Meijer Chris J.L.M. , Vaccarella Salvatore V. , Jara Alejandro T. , Puschel Klaus I. , Robles Sylvia C. , Herrero Rolando , Franceschi Silvia F. , Ojeda Jose M. 
Published: June 2022

Abstract
More than 18 types of human papillomavirus (HPV) are associated with cervical cancer, the relative importance of the HPV types may vary in different populations.
Objective: To investigate the types of HPV, age distribution, and risk factors for HPV infection in women from Santiago, Chile.
Methods: We interviewed and obtained two cervical specimens from a population-based random sample of 1,038 sexually active women (age range, 15-69 years). Specimens were tested for the presence of HPV DNA using a GP5+/6+ primer-mediated PCR and for cervical cytologic abnormalities by Papanicolaou smears.
Results: 122 women tested positive for HPV DNA, 87 with high risk types (HR), and 35 with low risks (LR) only. Standardized prevalence of HPV DNA was 14.0% [95% confidence interval (95% CI), 11.5-16.4]. HR HPV by age showed a J reverse curve, whereas LR HPV showed a U curve, both statistically significant in comparison with no effect or with a linear effect. We found 34 HPV types (13 HR and 21 LR); HPV 16, 56, 31, 58, 59, 18, and 52 accounted for 75.4% of HR infections. Thirty-four (3.6%) women had cytologic lesions. Main risk factor for HPV and for cytologic abnormalities was number of lifetime sexual partners, odds ratios for ≥3 versus 1 were 2.8 (95% CI, 1.6-5.0) and 3.8 (95% CI, 1.3-11.4), respectively.
Conclusions: LR HPV presented a clear bimodal age pattern; HR HPV presented a J reverse curve. HPV prevalence was similar to that described in most Latin American countries.
PCR Testing of Pooled Longitudinally Collected Cervical Specimens of Women to Increase the Efficiency of Studying Human Papillomavirus Infection
Authors: Castle Philip E. , Schiffman Mark , Herrero Rolando , Hildesheim Allan , Rodriguez Ana-Cecilia , Bratti M. Concepcion , Wacholder Sholom , Kendal Hortense , Breheny Anne M. , Prior Andrew , Pfeiffer Ruth , Burk Robert D. 
Published: June 2022

Abstract
In large active cohort studies of women investigating human papillomavirus (HPV) and cervical neoplasia, many women will be HPV-negative at all time points and testing of all their cervical specimens is an inefficient use of laboratory resources. The aim of this pilot study was to evaluate whether pooling cervical specimens from the same woman might provide a useful pretest of specimens from women unlikely to have high-grade cervical neoplasia or significant HPV exposure. We selected women (n = 187) participating in the Guanacaste Project for whom we already had HPV testing data on all their specimens from multiple visits (median = 8 visits), who were HPV DNA-negative at enrollment and at their 5- to 7-year exit from the cohort, and had no evidence of high-grade cervical neoplasia. Equal aliquots of cervical specimens from these women were pooled to create a proportional pooled specimen. Aliquots of pooled specimens were tested in a masked fashion by MY09/11 L1 consensus primer PCR. Second aliquots of some pooled specimens (n = 83) were included to assess the reliability of pooled testing. Results were compared with the predicted (expected) results based on the obtained test results of the individual specimens collected at interim visits. There was good overall agreement between observed and expected HPV DNA positivity, with a κ of 0.63 [95% confidence interval (95% CI), 0.51-0.75] and a percent agreement of 83.4% (95% CI, 77.3-88.5%) although the HPV DNA positivity in the pooled specimen was less than expected (P = 0.001). The agreement between observed and expected HPV DNA positivity was related to the number of aliquots pooled, suggesting that positivity was related to viral genome concentrations. The κ and percent agreement for intra-batch reliability of testing pooled specimens were 0.68 (95% CI, 0.53-0.84) and 84.3% (95% CI, 74.7-91.4%), respectively. We conclude that pooling specimens and testing by PCR may be useful for discriminating HPV DNA-positive from completely negative specimen sets in women who are likely to have been HPV DNA-negative.&gt;
Period3 Structural Variation: A Circadian Biomarker Associated with Breast Cancer in Young Women
Authors: Zhu Yong , Brown Heather N. , Zhang Yawei , Stevens Richard G. , Zheng Tongzhang 
Published: June 2022

Abstract
Circadian disruption has been indicated as a risk factor for breast cancer in recent epidemiologic studies. A novel finding in circadian biology is that genes responsible for circadian rhythm also regulate many other biological pathways, including cell proliferation, cell cycle regulation, and apoptosis. Therefore, mutations in circadian genes could conceivably result in deregulation of these processes and contribute to tumor development, and be markers for susceptibility to human cancer. In this study, we investigated the association between an exonic length variation in a circadian gene, Period3 (Per3), and breast cancer risk using blood samples collected from a recently completed breast cancer case-control study in Connecticut. There were 389 Caucasian cases and 432 Caucasian controls included in our analysis. We found that the variant Per3 genotype (heterozygous + homozygous 5-repeat alleles) was associated with an increased risk of breast cancer among premenopausal women (odds ratio, 1.7; 95% confidence interval, 1.0-3.0). Our finding suggests that the circadian genes might be a novel panel of potential biomarkers for breast cancer and worth further investigation.
Human Papillomavirus Capsid Antibody Response to Natural Infection and Risk of Subsequent HPV Infection in HIV-Positive and HIV-Negative Women
Authors: Viscidi Raphael P. , Snyder Brad , Cu-Uvin Susan , Hogan Joseph W. , Clayman Barbara , Klein Robert S. , Sobel Jack , Shah Keerti V. 
Published: June 2022

Abstract
The association between seropositivity to virus-like particles (VLP) of human papillomavirus (HPV) types 16, 18, 31, 35, or 45 and subsequent cervical HPV infection was examined in 829 women with HIV and 413 risk-matched HIV-negative women. We found no statistically significant differences between HPV-seropositive and HPV-seronegative women in the risk of a new infection with the homologous HPV type, with the exception of a reduced risk of HPV 45 infections 4.5 years beyond the baseline serology measurement in HIV-positive women [hazard ratio, 0.21; 95% confidence interval (CI), 0.05-0.89]. Among HIV-negative women, HPV seropositivity was not associated with a statistically significant reduced risk of infections with related viruses in the HPV 16, HPV 18, or “other” HPV groups. Among HIV-positive women, HPV seropositivity was associated with a slightly increased risk of infection with group-related viruses, but the differences were only statistically significant for infection with HPV 16 group viruses (hazard ratio, 1.6; 95% CI, 1.1-2.3) in HPV 18-seropositive women and for infections with “other” HPV group viruses in HPV 31-seropositive women (hazard ratio, 1.45; 95% CI, 1.0-2.0). The lack of a protective immune effect from natural infection is most likely due to the low level of antibody elicited by natural HPV infection and/or the potential for reactivation of HPV, especially in HIV-positive women.
The Association between Race and Attitudes about Predictive Genetic Testing
Authors: Peters Nikki , Rose Abigail , Armstrong Katrina 
Published: June 2022

AbstractObjective: To investigate differences in attitudes about predictive genetic testing for cancer risk between African-American and Caucasian residents of the city of Philadelphia. Methods: Cross-sectional survey of awareness of and attitudes about predictive genetic testing, using an instrument developed through focus groups with the general public, literature review, and expert opinion. Setting: Municipal County Courthouse of Philadelphia. Respondents: Male and female adults waiting to be assigned to jury duty. Results: Of the 430 respondents, 43% (170) were African-American and 45% (181) Caucasian. Awareness of predictive genetic testing was higher among Caucasians (72%) than African-Americans (49%). After adjustment for age, gender, and educational attainment, African-Americans were more likely to report that the government would use genetic tests to label groups as inferior, and less likely to endorse the potential health benefits of testing, including “help my doctor manage my health care,” “help me change my lifestyle,” and “help scientists find cures for diseases.” These associations remained if the sample was restricted to participants who had heard of genetic testing before the survey. Conclusions: In the city of Philadelphia, awareness of and attitudes about predictive genetic testing for cancer risk differ by race, with lower awareness, less belief in the potential benefits of testing, and more concern about racial discrimination from genetic testing among African-Americans than Caucasians. These differences may result in disparities in the uptake of predictive genetic testing in the future.
Demographic and Psychosocial Factors Associated with Perceived Risk for Colorectal Cancer
Authors: Robb Kathryn A. , Miles Anne , Wardle Jane 
Published: June 2022

Abstract
Objective: The objective of this study was to investigate demographic and psychosocial predictors of perceptions of risk for colorectal cancer (CRC) in a population-based sample. Method: The study was a cross-sectional survey of 18,447 men and women aged 55–64 years. A mailed questionnaire assessed perceived comparative risk for CRC along with demographic characteristics (age, gender, ethnicity, marital status, and socioeconomic status), health-related factors (family history, subjective health and bowel symptoms, and health behaviors), and emotional state (anxiety). Results: Being male and older were associated with lower perceived risk. Having a family history of CRC, poorer subjective health, more symptoms, and higher levels of anxiety were all associated with increased perceived risk of CRC. Smokers and nonexercisers perceived their risk as higher. Conclusion: Misperceptions surrounding the effects of age and gender on CRC risk, as well as the genetic link and pathogenesis of CRC, need to be addressed in risk communications.