bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nuclear Morphometry and Molecular Biomarkers of Actinic Keratosis, Sun-Damaged, and Nonexposed Skin
Authors: Carpenter Philip M. , Linden Kenneth G. , McLaren Christine E. , Li Kuo-Tung , Arain Shehla , Barr Ronald J. , Hite Pamela , Sun Joannie D. , Meyskens Frank L. 
Published: June 2022

AbstractComputer-assisted image analysis is useful for quantifying the histologic and molecular changes of sun-induced squamous cell carcinoma progression. We used the CAS 200 image analysis system to measure nuclear morphometric parameters, p53 expression, and proliferation markers in actinic keratosis (AK), sun-exposed, and normal skin in 51 patients. Nuclear morphometry revealed significant increases in nuclear absorbance, irregularity of nuclear shape, and nuclear size in AK compared with normal and sun-damaged skin. These parameters showed significantly greater variability in AK nuclei. Argyrophyllic nucleolar organizer area and number were also significantly greater in AK compared with sun-damaged skin and normal skin. Ki67 and p53 expressions were both increased in sun-damaged skin relative to normal and greater still in AK. These data are evidence that sun damage induces proliferation and p53 abnormalities before the appearance of nuclear abnormalities and their associated DNA instability. Following these changes during a skin cancer chemopreventative trial can then help assess the efficacy of the agent and help determine where in the progression of neoplastic changes it exerts its biological effects.
Sex Differences in Numbers of Nevi on Body Sites of Young European Children: Implications for the Etiology of Cutaneous Melanoma
Authors: Autier Philippe , Boniol Mathieu , Severi Gianluca , Pedeux Remy , Grivegnée André-Robert , Doré Jean-François ,   European Organisation for Research and Treatment of Cancer Melanoma Group
Published: June 2022

Abstract
Background: Since 1950, the greatest increase in cutaneous melanoma incidence in fair-skinned males took place on the trunk and on the head and neck, whereas in females, it took place on the limbs, mainly on the lower limbs. We examined the influence of sex on numbers and size of nevi on different body sites in white European schoolchildren.
Methods: Information about each holiday period since birth to interview was recorded from parents of six hundred twenty-eight 6- to 7-year-old children in four European cities (Brussels (Belgium), Bochum (Germany), Lyons (France), and Rome (Italy)). Number and anatomic location of small (2-4.9 mm) and large (≥5 mm) nevi and individual susceptibility to sunlight were independently assessed.
Results: After adjustment for host characteristics, sun exposure, and sun protection habits, males had 7% [95% confidence interval (95% CI), −7 to 19] more small nevi than females. However, compared to females, numbers of small nevi were increased by 17% (95% CI, 1-31) on the head and neck and by 16% (95% CI, 2-27) on the trunk and shoulders. In contrast, in males, the number of small nevi on upper limbs was decreased by −5% (95% CI, −26 to 13), and on lower limbs by −8% (95% CI, −34 to 13). The number of large nevi was 6% higher in males than in females (95% CI, −26 to 30).
Conclusions: The sex differences in small nevus distribution in schoolchildren reflect the sex differences in the anatomic distribution of melanoma in adults. Sex differences in sun exposure behaviors, dressing, and clothing would just add their effects to the sex-dependent inherited propensity to develop nevi on a given body site. These results reinforce the hypothesis by which childhood would be a decisive period for the occurrence of sun-induced biological events implicated in the genesis of cutaneous melanoma.
Plasma Enterolactone and Breast Cancer Incidence by Estrogen Receptor Status
Authors: Olsen Anja , Knudsen Knud Erik Bach , Thomsen Birthe L. , Loft Steffen , Stripp Connie , Overvad Kim , Møller Susanne , Tjønneland Anne 
Published: June 2022

AbstractThe phytoestrogen enterolactone has been hypothesized to prevent breast cancer. Because one of the biological effects of enterolactone is probably estrogenic, it is possible that the preventive effect on breast cancer differs with the estrogen receptor (ER) α status of the tumor. The objective of this study was to investigate whether high plasma levels of enterolactone are associated with breast cancer risk and whether the ERα status of the tumor influences this relation. The cohort study Diet, Cancer and Health included 29,785 women, ages 50 to 64 years, between 1993 and 1997. Information about diet and life-style factors was obtained by questionnaire, and blood was drawn from each participant. We matched 381 postmenopausal breast cancer cases to 381 controls and analyzed the concentration of enterolactone in plasma with a time-resolved fluoroimmunoassay. Associations between plasma concentrations of enterolactone and breast cancer were analyzed by logistic regression. The incidence rate ratio (IRR) for all breast cancer was 0.93 [95% confidence interval (CI), 0.86-1.01] per 20 nmol/L higher plasma concentration of enterolactone. For ERα-positive cancers (n=273) only a weak association was seen (IRR, 0.97; 95% CI, 0.88-1.06), whereas for ERα-negative cancers (n = 80; IRR, 0.71; 95% CI, 0.53-0.94) a protective effect was seen per 20 nmol/L higher plasma enterolactone. In accordance with earlier research, we found a tendency toward a lower risk for breast cancer with higher concentrations of enterolactone, which was restricted almost entirely to ERα-negative breast cancer.
Association of Genetic Variants in the Calcium-Sensing Receptor with Risk of Colorectal Adenoma
Authors: Peters Ulrike , Chatterjee Nilanjan , Yeager Meredith , Chanock Stephen J. , Schoen Robert E. , McGlynn Katherine A. , Church Timothy R. , Weissfeld Joel L. , Schatzkin Arthur , Hayes Richard B. 
Published: June 2022

AbstractObjective: Evidence suggests that calcium prevents colorectal cancer, possibly mediated through the calcium-sensing receptor (CASR). We assessed the associations between CASR gene variants and risk for colorectal adenoma, a cancer precursor. We further investigated gene-diet interactions between the CASR variants and calcium intake on adenoma risk.Methods: Individuals with advanced distal adenomas (n = 716) and controls with a negative sigmoidoscopy exam (n = 729) were randomly selected from participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Three nonsynonymous variants in the intracellular signaling region of CASR (A986S, R990G, Q1011E) were analyzed by Taqman.Results: Compared with the most common diplotype (haplotype pair), the odds ratios for advanced adenoma were 0.80 [95% confidence interval (CI), 0.60-1.06], 0.79 (95% CI, 0.55-1.13), and 0.56 (95% CI, 0.36-0.88) for the other three common diplotypes (&gt;5% frequency). Although calcium intake was inversely associated with adenoma risk, CASR diplotypes did not modify this association. However, the power to investigate interactions was limited.Conclusion: Variants in the CASR intracellular signaling region were significantly associated with the risk of advanced adenoma.
Urinary Estrogen Metabolites and Their Ratio among Asian American Women
Authors: Falk Roni T. , Fears Thomas R. , Xu Xia , Hoover Robert N. , Pike Malcolm C. , Wu Anna H. , Nomura Abraham M.Y. , Kolonel Laurence N. , West Dee W. , Sepkovic Daniel W. , Bradlow H. Leon , Ziegler Regina G. 
Published: June 2022

Abstract
Controversy persists regarding the role of a low ratio of 2-hydroxyestone (2-OHE1)/16α-hydroxyestrone (16α-OHE1) as a potential estrogen metabolism marker of increased risk for breast cancer. Most of the evidence has been provided by case-control studies, where tumor effects on hormone metabolism are not known. Studies in populations at various risk of breast cancer are not consistent, with some suggesting that levels of the ratio may be altered by changes in diet and exercise. We studied Asian American women participating as controls in a case-control study of breast cancer in which migration history—a composite of the subject's place of birth, type of residence in Asia (urban or rural), length of time living in the West, and grandparents' place of birth—was associated with a 6-fold risk gradient that paralleled the historical differences in incidence rates between the United States and Asian countries. This population offered the possibility to address whether the ratio of 2-OHE1:16α-OHE1 differs according to recognized breast cancer risk factors, including migration history. Overnight 12-hour urines were obtained from 368 premenopausal and 143 naturally postmenopausal women of Chinese, Japanese, or Filipino descent who donated urines between 1985 and 1988. The estrogen metabolites 2-OHE1 and 16α-OHE1 were measured with an ELISA kit and adjusted for creatinine levels. In each ethnic group, the ratio of 2-OHE1:16α-OHE1 was consistently lower in women born in the West than in those who had migrated from Asia. For premenopausal women, the ratio declined 20% due to lower levels of 2-OHE1. Among postmenopausal women, the ratio was 23% lower in those born in the West, but no consistent patterns based on place of birth were observed for either 2-OHE1 or 16α-OHE1. The ratio did not vary with most recognized breast cancer risk factors, except for lower metabolite ratios in women with a younger age at first birth and more children, which runs contrary to the hypothesis, because both characteristics reduce breast cancer risk. Our study suggests that the ratio of 2-OHE1:16α-OHE1 may be a marker for lifestyle influences on estrogen metabolism associated with westernization.
Randomized Study of High-Dose Pulse Calcitriol or Placebo prior to Radical Prostatectomy
Authors: Beer Tomasz M. , Myrthue Anne , Garzotto Mark , O'Hara Michael F. , Chin Raymond , Lowe Bruce A. , Montalto Michelle A. , Corless Christopher L. , Henner W. David 
Published: June 2022

Abstract
Background: Cancer chemoprevention trials require enormous resources due to the large numbers of patients and the years of follow-up needed to achieve sufficient statistical power. Examination of candidate prevention agents using biomarkers as surrogate end points has been proposed as a method to rapidly identify promising agents for prevention trials. Treatment of patients with candidate agents prior to scheduled biopsy or surgical resection of malignancy allows for direct examination of the treatment effects on tumor tissue. In this study, we selected this approach to test several hypotheses about the effect of calcitriol (1,25-dihydroxycholecalciferol), the active form of vitamin D, on early-stage human prostate cancer.
Methods: After selection of surgical treatment for histologically confirmed adenocarcinoma of the prostate, patients were randomized to either calcitriol 0.5 μg/kg or placebo weekly for 4 weeks. The expression levels of the vitamin D receptor (VDR), proliferating cell nuclear antigen, PTEN (MMAC1/TEP1), c-Myc, transforming growth factor (TGF) β receptor type II (TGFβ RII), and Bcl-2 were quantified using immunohistochemistry in the patients' prostate specimens post surgery.
Results: Thirty-seven of 39 prostate tumors were evaluable for molecular end points. VDR expression was reduced in patients treated with calcitriol (mean, 75.3% of cells) compared with those that received placebo (mean, 98.6%; P = 0.005). Calcitriol treatment did not result in a statistically significant change in the fraction of cells expressing TGFβ RII, PTEN, or proliferating cell nuclear antigen. Bcl-2 and c-Myc expression was at the lower limits of detection in both the calcitriol group and the placebo group; therefore, we were unable to determine whether drug treatment induced a significant change in these biomarkers.
Conclusions: High-dose calcitriol down-regulates VDR expression in human prostate cancer. Further study is needed to determine the biological consequences of VDR down-regulation in prostate cancer. This study shows that the use of the preprostatectomy model is feasible and can be used to test the effect of candidate chemopreventive agents on prostate cancer.
Comparison of Archival Plasma and Formalin-Fixed Paraffin-Embedded Tissue for Genotyping in Hepatocellular Carcinoma
Authors: Sjöholm Malin I.L. , Hoffmann Gunilla , Lindgren Stefan , Dillner Joakim , Carlson Joyce 
Published: June 2022

Abstract
Biobanks containing formalin-fixed paraffin-embedded tissue, as well as frozen serum or plasma, are important resources for molecular epidemiologic studies. However, few studies have compared the reliability of formalin-fixed tissue samples and archival plasma samples for genotyping. We determined the genotype of four proposed genetic risk factors for hepatocellular carcinoma [hereditary hemochromatosis (HFE 63 and 282), α1-antitrypsin deficiency (AAT 342) and cystic fibrosis (CFTR 508)] on formalin-fixed tissue samples, stored for up to 25 years, from 318 patients diagnosed with hepatocellular carcinoma and on plasma or serum samples from 31 of these patients. The genotypes were analyzed by RFLP or allele-specific amplification as well as by TaqMan assays. In addition, genotyping was attempted after whole genome amplification by multiple displacement amplification (MDA). Genotyping was successful in 94% of the tissue samples and successful and identical to the tissue samples from the same subjects in 98% of the plasma/serum samples. DNA from plasma samples could be amplified &gt;5,000-fold by MDA and genotyping after MDA gave identical results to the genotyping of the same subjects before whole genome amplification. MDA amplification of the tissue samples was not successful. In summary, archival plasma was found to be an adequate source of efficiently amplifiable DNA. MDA on plasma samples allows analysis of multiple genotypes in epidemiologic studies.
Vitamin E Supplements and Risk of Prostate Cancer in U.S. Men
Authors: Rodriguez Carmen , Jacobs Eric J. , Mondul Alison M. , Calle Eugenia E. , McCullough Marjorie L. , Thun Michael J. 
Published: June 2022

Abstract
Supplementation with α-tocopherol (a form of vitamin E) was associated with decreased risk of prostate cancer in a randomized trial among Finnish smokers. We examined the association between vitamin E supplement use and prostate cancer incidence in the Cancer Prevention Study II Nutrition Cohort. Participants in the study completed a detailed questionnaire at enrollment in 1992–1993. Historical information was also available from a questionnaire completed in 1982 at enrollment in a previous cohort. Through August 31, 1999, we documented 4,281 cases of incident prostate cancer among 72,704 men. Multivariate-adjusted rate ratios (RRs) were calculated using Cox Proportional Hazards models. Regular vitamin E supplement use (≥4 times per week) was not associated with overall risk of prostate cancer or with risk of advanced prostate cancer at diagnosis. No trend was seen with increasing dose of vitamin E. Men who reported regular vitamin E use in both 1982 and in 1992–1993 were not at lower risk of prostate cancer. Among current smokers, there was a suggestion of slightly reduced risk with regular vitamin E supplement use [RR = 0.87, 95% confidence interval (CI) = 0.67–1.11]. Our results do not support an important role for vitamin E supplements in prostate cancer prevention.
Distribution of Persistent, Lipid-Soluble Chemicals in Breast and Abdominal Adipose Tissues: Lessons Learned from a Breast Cancer Study
Authors: Petreas Myrto , Smith Daniel , Hurley Susan , Jeffrey Stefanie S. , Gilliss Debra , Reynolds Peggy 
Published: June 2022

Abstract
Objective: We sought to determine differences between concentrations of persistent, lipid-soluble chemical contaminants in breast and abdominal adipose tissues and to explore whether concentrations measured in one tissue could predict concentrations in the other tissue. Methods: We analyzed surgical specimens and measured concentrations of prevalent dioxins, furans, polychlorinated biphenyls, organochlorine pesticides, and brominated diphenyl ethers to determine their partitioning between breast and abdominal adipose tissues of 21 women. The women constituted a subgroup, undergoing mastectomies with simultaneous breast reconstruction, of a case-control study evaluating links between breast cancer and body burdens of organohalogen contaminants. Results: For every contaminant, differences between concentrations in breast and abdominal adipose tissues did not exceed the analytical error. Results indicated that, with some notable exceptions, measurements in breast and abdominal adipose tissues were correlated and that concentrations of target chemicals in one tissue could be derived from measurements in the other tissue. Conclusions: This information will allow comparison of results from body burden studies that used different tissues. It may also facilitate future breast cancer studies by allowing selection of controls among patients undergoing surgical procedures other than breast surgery, minimizing concerns about overmatching. We also observed large differences in the lipid content of surgical specimens. These differences underscore the need for lipid adjustment of concentrations to avoid misclassification.
Environmental Factors in Helicobacter pylori-Related Gastric Precancerous Lesions in Venezuela
Authors: Kato Ikuko , Vivas Jorge , Plummer Martyn , Lopez Gladys , Peraza Simon , Castro Dennis , Sanchez Victor , Cano Elsa , Andrade Olga , Garcia Rita , Franceschi Silvia , Oliver Walter , Muñoz Nubia 
Published: June 2022

Abstract
Although Helicobacter pylori (HP) infection has been acknowledged to play an etiological role in gastric carcinogenesis, its relatively weak association particularly in developing countries suggests critical roles of cofactors. Among a population with an extremely high prevalence of HP infection (≈95%) in Venezuela, we examined the relationship of household characteristics, smoking, alcohol drinking, dietary consumption, and plasma nutrient levels with the prevalence of three different stages of gastric precancerous lesions, chronic atrophic gastritis (AG; n = 337), intestinal metaplasia (IM; n = 551), and dysplasia (n = 157), in comparison with those without any of these lesions (n = 1154). Length of refrigerator use was marginally inversely associated with the prevalence of the precursor lesions studied. The association was most pronounced for AG followed by dysplasia. On the other hand, smoking status was a significant predictor for IM and dysplasia. Those smoking ≥10 cigarettes/day had 1.8-fold risk of IM and 3.6-fold risk of dysplasia compared with never smokers. There were no associations with alcohol consumption. When six food groups known to be associated with stomach cancer risk in Venezuela were tested, the prevalence of these lesions progressively increased with increasing starchy vegetable consumption and decreasing fresh fruit/fruit juice consumption. The association with fruits was more evident for dysplasia and AG and that with starchy vegetables for IM and AG. However, there were no inverse associations with plasma antioxidant vitamins. These findings offer important public health implications in preventing progression of HP-associated gastric precancerous lesions in high-risk populations.
Aspirin, NSAIDs, and Colorectal Cancer: Possible Involvement in an Insulin-Related Pathway
Authors: Slattery Martha L. , Samowitz Wade , Hoffman Michael , Ma Khi Ne , Levin Theodore R. , Neuhausen Susan 
Published: June 2022

Abstract
Introduction: Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce risk of colorectal cancer. Although inhibition of cyclooxygenase (COX)-2 is generally thought to be the relevant mechanism, aspirin-like drugs apparently are involved in other pathways and mechanisms. We explore the associations between aspirin/NSAIDs, the insulin-related pathway, and the risk of colorectal cancer. Methods: Genetic polymorphisms of five genes identified as being involved in an insulin-related pathway were genotyped using data collected in a case-control study of 1346 incident colon cancer cases and 1544 population-based controls and 952 incident rectal cancer cases and 1205 controls. Genotypes assessed were the 3′ untranslated region poly(A) and the intron 8 BsmI polymorphisms of the VDR gene, a CA repeat polymorphism of the IGF1 gene, the A/C polymorphism at nucleotide −202 of the IGFBP3, the Gly972Arg polymorphism of the IRS1 gene, and the Gly1057Asp polymorphism of the IRS2 gene. Results: Use of aspirin and NSAIDs was associated with a decreased risk of colorectal cancer, with slightly greater protection from NSAIDs than aspirin for rectal cancer. We observed a significant interaction between IRS1 genotype and aspirin/NSAIDs use and risk of colorectal cancer. Relative to the GR/RR IRS1 genotype, a protective effect from the GG IRS1 genotype was seen in those who did not use NSAIDs; use of NSAIDs was protective for all genotypes. These associations were especially strong for those diagnosed prior to age 65 (P interaction = 0.0006). We also observed a significant interaction between aspirin/NSAIDs use and the VDR gene. Having the SS or BB VDR genotypes reduced risk of colorectal cancer among non-aspirin/NSAID users; however, aspirin/NSAIDs reduced risk for all VDR genotypes. Conclusions: These data support the protective effect of aspirin and NSAIDs on colorectal cancer risk. In addition, the observed interactions for aspirin/NSAIDs and IRS1 and VDR genotypes suggest that mechanisms other than COX-2 inhibition may be contributing to the protective effect of aspirin and NSAIDs on colorectal cancer risk.
Pap Testing Adherence among Vietnamese American Women
Authors: Taylor Victoria M. , Yasui Yutaka , Burke Nancy , Nguyen Tung , Acorda Elizabeth , Thai Hue , Qu Pingping , Jackson J. Carey 
Published: June 2022

AbstractObjectives: Vietnamese American women are five times more likely to be diagnosed with cervical cancer than their White counterparts. Previous research has demonstrated low levels of Papanicolaou (Pap) testing among Vietnamese. Our study objective was to examine factors associated with interval Pap testing adherence. Methods: A population-based, in-person survey of Vietnamese women aged 18–64 years was conducted. Questionnaire content was guided by the Health Behavior Framework (HBF). The study sample was randomly selected from 1639 south Seattle households. Statistical methods included χ2 tests and logistic regression. Results: The response rate among eligible households was 82%, and the study included 352 women. Sixty-eight percent of the participants had been screened during the preceding 3 years. The following HBF factors were associated (P &lt; 0.05) with interval Pap testing in bivariate comparisons: believing Pap tests decrease the risk of cervical cancer and believing cervical cancer is curable if detected early (perceived effectiveness); knowing testing is necessary for women who are asymptomatic, sexually inactive, or postmenopausal (knowledge); reporting concern about pain/discomfort as a barrier to screening (barriers); family member(s) and friend(s) had suggested testing (social support); doctor(s) had recommended testing; and had asked doctor(s) for testing (communication with provider). In a multivariate analysis, being married, knowing Pap testing is necessary for asymptomatic women, doctor(s) had recommended testing, and had asked doctor(s) for testing were independently associated (P &lt; 0.05) with screening participation. Conclusion: Our results confirm low levels of Pap testing among Vietnamese women and demonstrate the importance of physician-patient communication in increasing screening adherence. Health education efforts should target unmarried women and reinforce the importance of Pap testing for all Vietnamese women.