bluuebunny/crossref_metadata_2025 huggingface dataset:
Cyclooxygenase-2 and p53 Expressions in Endometrial Cancer
Authors: Jeon Yong-Tark , Kang Sokbom , Kang Dae-Hee , Yoo Keun-Young , Park In-Ae , Bang Yung-Jue , Kim Jae Weon , Park Noh-Hyun , Kang Soon-Beom , Lee Hyo-Pyo , Song Yong-Sang
Published: June 2022

Cyclooxygenase-2 (COX-2) has been known to be related with various types of carcinoma, but we have insufficient knowledge about the association between COX-2 and endometrial cancer. Many have reported a close relationship between p53 expression and a poor prognosis in endometrial cancer, but it is unclear whether p53 is an independent prognostic factor. To clarify these uncertainties, we examined the expressions of COX-2 and p53 in endometrial cancer tissues. The study was carried on 152 endometrial cancer patients who had operation at Seoul National University Hospital. Paraffin-embedded tissue blocks were sectioned and immunostained using monoclonal anti-COX-2 and anti-p53 antibodies. Twenty-seven (17.8%) specimens stained as COX-2 positive. COX-2 positivity was more frequently observed in postmenopausal patients than in premenopausal patients (8.8% versus 25.0%; P = 0.009). However, COX-2 positivity did not show a statistically significant association with any other clinicopathologic characteristic (parity, body mass index, histotype, International Federation of Gynecology and Obstetrics stage, grade, lymph node metastasis, deep myometrial invasion, or p53 overexpression). Thirty-one (20.4%) specimens showed p53 overexpression and this was significantly correlated with an advanced stage (P = 0.001), poor differentiation (P < 0.001), lymph node metastasis (P = 0.012), and deep myometrial invasion (P < 0.001). Multivariate Cox regression analysis showed that advanced stage was an independent prognostic factor of survival, but p53 overexpression was not. COX-2 may be associated with endometrial cancer carcinogenesis during the postmenopausal period but not with tumor aggressiveness and p53 overexpression. The p53 overexpression was found to be strongly associated with endometrial cancer aggressiveness.
Hemochromatosis Gene Mutations and Distal Adenomatous Colorectal Polyps
Authors: McGlynn Katherine A. , Sakoda Lori C. , Hu Ying , Schoen Robert E. , Bresalier Robert S. , Yeager Meredith , Chanock Stephen , Hayes Richard B. , Buetow Kenneth H.
Published: June 2022

Iron has been suggested to be a risk factor for colorectal neoplasia. Some individuals who are heterozygous for mutations in the hemochromatosis gene (HFE) have higher than average serologic measures of iron. We therefore investigated whether heterozygosity for HFE mutations was related to risk of advanced distal adenoma and whether the relationship was affected by dietary iron intake. In the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, 679 persons with advanced distal adenoma and 697 control persons were genotyped for the two major HFE mutations (C282Y and H63D), one HFE polymorphism (IVS2+4), and one polymorphism (G142S) in the transferrin receptor gene (TFRC). HFE haplotypes were also created to examine the effect of haplotype on risk. Food frequency questionnaire data were used to estimate daily iron intake. There was no relationship between any HFE genotype or haplotype and advanced adenoma. Stratification of HFE genotype by TFRC genotype did not change the results. In addition, there was no relationship between dietary iron intake and risk of adenoma or between HFE genotype and risk of adenoma, stratified by iron intake. These results do not support a relationship between HFE heterozygosity and risk of advanced distal adenoma.
Dietary Factors and Risk of Non-Hodgkin Lymphoma by Histologic Subtype: A Case-Control Analysis
Authors: Purdue Mark P. , Bassani Diego G. , Klar Neil S. , Sloan Margaret , Kreiger Nancy ,   The Canadian Cancer Registries Epidemiology Research Group
Published: June 2022

There is speculation that etiologic heterogeneity exists among tumors classified as non-Hodgkin lymphoma (NHL), although it is not known whether diet-related associations vary between tumor subgroups. We analyzed data on 1,642 NHL cases and 5,039 controls aged 20 to 74 years from a population-based case-control study conducted in eight Canadian provinces to explore associations between dietary factors and NHL by histologic subtype. Dietary information was collected using a 69-item food frequency questionnaire. Tumors were categorized into histologic subtypes using the contents of pathology reports from the original histopathologic review of diagnostic material. Odds ratios (OR) relating consumption of dietary factors (divided into three categories) to each NHL subtype (diffuse, follicular, small lymphocytic, high grade, peripheral T cell, and unspecified lymphomas) were calculated using polytomous logistic regression. We found an increased risk of NHL with high (versus low) intake of processed meat (OR, 1.49), cheese (OR, 1.38), eggs (OR, 1.49), and dessert foods (OR, 1.24). Positive associations with NHL were also found for high consumption of total fat (OR, 1.28), saturated fat (OR, 1.29), and monounsaturated fat (OR, 1.27). Associations for consumption of some vegetables and fats were found to differ between lymphoma subtypes. Given the large number of diet/subtype comparisons done, however, the possibility that this heterogeneity arose by chance cannot be ruled out. In conclusion, these findings generally do not support the existence of etiologic heterogeneity between histologic subtypes of NHL in their associations with components of dietary intake.
Serum Oxidized Low-Density Lipoprotein Levels and Risk of Colorectal Cancer: A Case-Control Study Nested in the Japan Collaborative Cohort Study
Authors: Suzuki Koji , Ito Yoshinori , Wakai Kenji , Kawado Miyuki , Hashimoto Shuji , Toyoshima Hideaki , Kojima Masayo , Tokudome Shinkan , Hayakawa Norihiko , Watanabe Yoshiyuki , Tamakoshi Koji , Suzuki Sadao , Ozasa Kotaro , Tamakoshi Akiko ,   Japan Collaborative Cohort Study Group
Published: June 2022

Oxidative stress plays an important role in carcinogenesis, but few epidemiologic studies have examined associations with risk of colorectal cancer. Relationships between serum levels of oxidized low-density lipoprotein (oxLDL) and oxLDL antibody (oLAB) and colorectal cancer risk were investigated in a case-control study nested in the Japan Collaborative Cohort Study for Evaluation of Cancer Risk. Serum samples and lifestyle information were collected at baseline from 39,242 men and women between 1988 and 1990. Of these, 161 incidents and deaths from colorectal cancer were identified through 1999, and 395 controls were matched for gender, age, and study area. Measurements were taken of serum oxLDL levels in 119 cases and 316 controls and serum oLAB levels in 153 cases and 376 controls. Odds ratios (95% confidence intervals) across quartiles, adjusted for confounding factors, were 1.55 (0.70-3.46), 1.90 (0.84-4.28), and 3.65 (1.50-8.92) for oxLDL (Ptrend = 0.004) and 0.98 (0.54-1.80), 0.75 (0.39-1.48), and 1.68 (0.90-3.13) for oLAB (Ptrend = 0.140). Further adjustment for serum total cholesterol and α-tocopherol did not materially change these associations. Odds ratio (95% confidence interval) of the highest quartile of serum oxLDL compared with the lowest quartile was 3.40 (1.09-10.58; Ptrend = 0.045). Analyses restricted to colon cancer cases and corresponding controls yielded similar relationships between serum oxLDL and oLAB levels and risk. In conclusion, higher levels of serum oxLDL may increase risk of colorectal cancer.
Effects of False-Positive Prostate Cancer Screening Results on Subsequent Prostate Cancer Screening Behavior
Authors: Ford Marvella E. , Havstad Suzanne L. , Demers Ray , Cole Johnson Christine
Published: June 2022

Objectives: Little is known about screening behavior following a false-positive prostate cancer screening result, which we have defined as a screening result with “abnormal/suspicious” labeling that did not result in a prostate cancer diagnosis within 14 months. The purpose of this analysis was to examine whether age, race, education, or previous false-positive prostate cancer screening results via prostate-specific antigen or digital rectal exam predict decision to obtain subsequent prostate cancer screening.

Methods: Data were drawn from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. The study sample consisted of 2,290 older men (mean age, 62.8 years; range, 55-75 years) who had false-positive (n = 318) or negative (n = 1,972) prostate-specific antigen or digital rectal exam baseline prostate cancer screening results. Multivariable logistic regression was used to assess the effect of false-positive results on subsequent prostate cancer screening behavior, adjusting for all covariates.

Results: The multivariable model showed that being African American (P = 0.016), and having a high school education or less (P = 0.007), having a previous false-positive prostate cancer screening result (P < 0.001), were predictive of not returning for prostate cancer screening in the following screening trial year.

Conclusion: The study results highlight the importance of shared decision making between patients and their providers regarding the risks and benefits of prostate cancer screening, and follow-up options for abnormal prostate cancer screening results. Shared decision making may be especially important for African American men, whom prostate cancer disproportionately affects.
Polymorphism in the DNA Repair Gene XPD, Polycyclic Aromatic Hydrocarbon-DNA Adducts, Cigarette Smoking, and Breast Cancer Risk
Authors: Terry Mary Beth , Gammon Marilie D. , Zhang Fang Fang , Eng Sybil M. , Sagiv Sharon K. , Paykin Andrea B. , Wang Qiao , Hayes Sharon , Teitelbaum Susan L. , Neugut Alfred I. , Santella Regina M.
Published: June 2022

DNA repair is essential to an individual's ability to respond to damage caused by environmental carcinogens. Alterations in DNA repair genes may affect cancer risk by influencing individual susceptibility to environmental exposures. XPD, a gene involved in nucleotide excision repair, may influence individual DNA repair capacity particularly of bulky adducts. Using a population-based breast cancer case-control study that was specifically conducted to examine markers of environmental exposures, such as polycyclic aromatic hydrocarbons (PAH), on Long Island, NY, we examined whether XPD genotype modified the associations among PAH-DNA adducts, cigarette smoking, and breast cancer risk. Specifically, we examined the XPD polymorphism at exon 23, position 751 in 1,053 breast cancer cases and 1,102 population-based controls. The presence of at least one variant allele (Lys/Gln or Gln/Gln) was associated with a 20% increase in risk of breast cancer [odds ratio (OR), 1.21; 95% confidence interval (95% CI), 1.01-1.44]. The increase in risk for homozygosity of the variant allele (Gln/Gln) seemed limited to those with PAH-DNA adduct levels above the median(OR, 1.61; 95% CI, 0.99-2.63 for adducts above the median versus OR, 1.05; 95% CI, 0.64-1.74 for adductsbelow the median), although the multiplicative interaction was not statistically significant. The increasein risk for homozygosity of the variant allele (Gln/Gln) was only seen among current smokers (OR, 1.97; 95% CI, 1.02-3.81 for current smokers versus OR, 0.87; 95% CI, 0.57-1.32 for never smokers); the multiplicative interaction was statistically significant. Overall, this study suggests that those individuals with this polymorphism in the XPD gene may face an increased risk of breast cancer from PAH-DNA adducts and cigarette smoking.
Estrogen and Risk of Gastric Cancer: A Protective Effect in a Nationwide Cohort Study of Patients with Prostate Cancer in Sweden
Authors: Lindblad Mats , Ye Weimin , Rubio Carlos , Lagergren Jesper
Published: June 2022

Background: The global pattern of male predominance in gastric cancer incidence remains unexplained. We tested the hypothesis that estrogen prevents gastric cancer in a cohort of men heavily exposed to estrogen.

Methods: We conducted a nationwide cohort study of men with a diagnosis of prostate cancer recorded in the Swedish Cancer Register in 1961-2000. Because estrogen therapy was the treatment of choice for prostate cancer in Sweden between 1950 and 1980, cohort members diagnosed earlier than 1980 were considered exposed to estrogen. Standardized incidence ratios (SIR) estimated relative risk. Complete follow-up was achieved through cross-linkages within the cancer register and the Swedish nationwide registers of emigration and causes of death.

Results: In 515,961 person-years of follow-up, we observed 304 gastric cancers as compared with 349 expected for the cohort members in the predefined “exposed” period 1961-1980, rendering a 13% decreased risk (SIR, 0.87; 95% confidence interval (95% CI), 0.78-0.98). Among patients with a latency of ≥15 years after a prostate cancer diagnosis in 1961-1980, SIR was 0.57 (95% CI, 0.30-0.97), suggesting a dose-response relation. Similarly, reduced risks were found for cardia cancer and noncardia gastric cancer. No decreased risk was found for the cohort members in 1981-2000, when estrogen treatment was less common (SIR, 0.99; 95% CI, 0.89-1.11).

Conclusions: Our study indicates a reduced risk of gastric cancer in a male cohort exposed to estrogen. These results support the hypothesis that estrogen may prevent gastric cancer, but additional studies are warranted.
Association between the Risk for Lung Adenocarcinoma and a (−4) G-to-A Polymorphism in the XPA Gene
Authors: Butkiewicz Dorota , Popanda Odilia , Risch Angela , Edler Lutz , Dienemann Hendrik , Schulz Volker , Kayser Klaus , Drings Peter , Bartsch Helmut , Schmezer Peter
Published: June 2022

Polymorphisms of genes coding for DNA repair can affect lung cancer risk. A common single nucleotide (−4) G-to-A polymorphism was identified previously in the 5′ untranslated region of the XPA gene. In a case-control study in European Caucasians, the influence of this polymorphism on primary lung cancer risk overall and according to histologic subtypes was investigated. Four hundred sixty-three lung cancer cases (including 204 adenocarcinoma and 212 squamous cell carcinoma) and 460 tumor-free hospital controls were investigated using PCR amplification and melting point analysis of sequence-specific hybridization probes. Odds ratios (OR) were calculated by multiple logistic regression analysis adjusting for age, gender, smoking habits, and occupational exposure and showed a slightly enhanced risk for all lung cancer cases as well as for squamous cell carcinoma and adenocarcinoma cases. Gene-environment interactions were analyzed with respect to smoking and occupational exposure. A nearly 3-fold increased risk for adenocarcinoma associated with the XPA AA genotype was observed for occupationally exposed individuals (OR, 2.95; 95% confidence interval, 1.42-6.14) and for heavy smokers (OR, 2.52; 95% confidence interval, 1.17-5.42). No genotype-dependent increase in OR was found for nonexposed individuals or those smoking <20 pack-years. The significant effect of the XPA polymorphism in heavy smokers and occupationally exposed individuals suggests an important gene-environment interaction for the XPA gene. The underlying mechanisms as to why AA homozygotes are predisposed to lung adenocarcinoma and which specific carcinogens are involved remains to be determined.
Insulin-Like Growth Factor (IGF)-1, IGF-Binding Protein-3, and Pancreatic Cancer in Male Smokers
Authors: Stolzenberg-Solomon Rachael Z. , Limburg Paul , Pollak Michael , Taylor Philip R. , Virtamo Jarmo , Albanes Demetrius
Published: June 2022

To investigate whether insulin-like growth factor (IGF)-1 and IGF-binding protein-3 (IGFBP-3) are prospectively associated with exocrine pancreatic cancer, we conducted a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort of 29,133 male Finnish smokers, aged 50–69 years. To avoid the potential influence of subclinical cancer on IGF-1 and IGFBP-3, all subjects in this study were alive without clinical evidence of cancer during their 5th year of the cohort follow-up. Four hundred randomly selected cohort controls and 93 incident pancreatic adenocarcinoma cases that occurred between their 5th follow-up year through 1997 (i.e., up to 12.7 years of follow-up) were included in this study. Concentrations of IGF-1 and IGFBP-3 were measured in serum samples obtained at baseline using ELISA. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression models, adjusted for confounders. Neither IGF-1, IGFBP-3, nor the IGF-1:IGFBP-3 molar ratio was significantly associated with pancreatic cancer: highest compared to lowest tertile, OR = 0.67, 95% CI 0.37–1.21, P trend = 0.17; OR = 0.70, 95% CI 0.38–1.27, P trend = 0.12; and OR = 0.85, 95% CI 0.50–1.46, P trend = 0.54, respectively. Our results do not support the hypothesis that serum IGF-1 and IGFBP-3 concentrations are associated with pancreatic cancer risk among male smokers. Further studies are necessary to evaluate these associations in other populations.
Smoking Status and Occupational Exposure Affects Oxidative DNA Injury in Boilermakers Exposed to Metal Fume and Residual Oil Fly Ash
Authors: Mukherjee Sutapa , Palmer Lyle J. , Kim Jee Young , Aeschliman David B. , Houk Robert S. , Woodin Mark A. , Christiani David C.
Published: June 2022

Epidemiologic studies demonstrate increased cancer incidence among workers exposed to polycyclic aromatic hydrocarbons (PAH) and metals, probably through cumulative oxidative DNA damage in response to carcinogens. Boilermakers are exposed to particulates of residual oil fly ash (ROFA) and metal fume that contain carcinogenic PAH and metals. We conducted a repeated-measures cohort study in boilermakers during the overhaul of an oil-fired boiler to determine a possible association between the level of 8-hydroxy-2′-deoxyguanosine (8-OH-dG; an oxidative injury biomarker) and biomarkers of PAH (1-hydroxypyrene; 1-OHP) and metal exposure. Preshift and postshift urine samples were analyzed for 8-OH-dG, cotinine, 1-OHP, and metals. Generalized estimating equations were used to model the multivariate relationship of 8-OH-dG to the explanatory variables of interest. Biomarker levels were determined for 181 urine samples from 20 male subjects (mean age 45 years, 50% smokers). Metal and 1-OHP levels increased cross-week and were affected by smoking status. Levels of 8-OH-dG were higher in nonsmokers at the start of the workweek yet declined after occupational exposure to similar levels as in smokers. Multivariate analysis indicated that metal × cotinine interaction terms for nickel, vanadium, chromium, and copper were significantly associated with the 8-OH-dG level, but there were differential effects depending on the metal. This study suggests that oxidative DNA damage in boilermakers is influenced by the interaction between occupational exposures and smoking status. In addition, boilermakers may have reduced ability to repair damaged DNA after ROFA and metal fume exposure. This finding has clinical relevance because these exposures may increase the cancer susceptibility of boilermakers.
Agricultural Pesticide Use, Familial Cancer, and Risk of Non-Hodgkin Lymphoma
Authors: Chiu Brian C-H , Weisenburger Dennis D. , Zahm Shelia Hoar , Cantor Kenneth P. , Gapstur Susan M. , Holmes Frederick , Burmeister Leon F. , Blair Aaron
Published: June 2022

To investigate whether the association between agricultural pesticide use and the risk of non-Hodgkin's lymphoma (NHL) is modified by a family history of hematopoietic cancer, including leukemia, myeloma, and lymphoma, we analyzed pooled data on white men from three population-based, case-control studies of NHL conducted in Iowa/Minnesota, Kansas, and Nebraska. Information on the agricultural use of insecticides, fungicides, and herbicides; a family history of cancer; and other risk factors was obtained by interviewing 973 cases and 2,853 controls or, if deceased, their next-of-kin (37% of cases, 43% of controls). The NHL risk was estimated by odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for age, state of residence, type of respondent, and use of hair dye. Compared to men with no family history of cancer, the ORs (95% CIs) of NHL was 1.5 (1.3–1.8) for men with a family history of nonhematopoietic cancer, and 2.7 (1.9–3.7) for those with a history of hematopoietic cancer among first-degree relatives. This positive association was noted for each group of NHL defined according to the Working Formulation, and was most pronounced for small lymphocytic NHL. Among direct respondents, farmers who used pesticides and had a positive family history of cancer or hematopoietic cancer were not at elevated risk of NHL, compared to nonfarmers who had no family cancer history. However, among proxy respondents, ORs were elevated for farmers who had a positive family history of hematopoietic cancer and used animal insecticides (OR = 4.6; 1.9–11.2), crop insecticides (OR = 4.7; 1.6–13.4), or herbicides (OR = 4.9; 1.7–14.2), although the interaction of family history of cancer and agricultural pesticide use was not statistically significant. In summary, the joint effects of the family cancer history and pesticide use were limited to proxy respondents with wide CIs and, thus, provide little evidence that a family history of cancer modifies the association of agricultural exposures with NHL.
Dietary Patterns and Risk of Breast Cancer in the ORDET Cohort
Authors: Sieri Sabina , Krogh Vittorio , Pala Valeria , Muti Paola , Micheli Andrea , Evangelista Alberto , Tagliabue Giovanna , Berrino Franco
Published: June 2022

The aim of this study was to evaluate the association between dietary patterns and risk of developing breast cancer in an Italian cohort. Women volunteers were recruited from 1987 to 1992 from residents in Varese province, northern Italy, an area covered by a cancer registry. Participants completed a semiquantitative food frequency questionnaire, and anthropometric and other data were collected systematically. Using nutritional data from 8984 women with an average follow up of 9.5 years and 207 incident cases of breast cancer, we conducted an exploratory factor analysis to identify major dietary patterns. Four dietary patterns, which explained 30% of the variance, emerged: salad vegetables (mainly consisting of raw vegetables and olive oil); western (mainly consisting of potatoes, red meat, eggs and butter); canteen (pasta and tomato sauce); and prudent (cooked vegetables, pulses, and fish, with negative loading on wines and spirits). After adjustment for potential confounders, only the salad vegetables pattern was associated with significantly lower (34–35%) breast cancer incidence (RR = 0.66, CI95% = 0.47±0.95 comparing highest with lowest tertile) with a significant linear trend (P = 0.016). Women with body mass index <25 had an even greater risk reduction in the highest tertile of the salad vegetables pattern (>50% less risk than the lowest tertile, RR = 0.39, CI95% = 0.22–0.69) with a significant trend (P = 0.001); whereas women with body mass index ≥25 had no protective effect for the consumption of salad vegetables. These findings suggest that a diet rich in raw vegetables and olive oil protects against breast cancer.
Cell Type Specificity of Lung Cancer Associated with Arsenic Ingestion
Authors: Guo How-Ran , Wang Nai-San , Hu Howard , Monson Richard R.
Published: June 2022

Arsenic is a well-documented human carcinogen. Previous studies on urinary bladder and skin cancers have shown that arsenic can cause specific cell types of malignancy. To evaluate whether this is also true for lung cancers, we conducted a study on 243 townships in Taiwan. We identified patients through the National Cancer Registry Program and compared the proportion of each major cell type between an endemic area of arsenic intoxication with exposures through drinking water, which includes 5 of the townships and the other 238 townships. To control for gender and age, we analyzed data on men and women separately and divided patients into four age groups. A total of 37,290 lung cancer patients, including 26,850 men and 10,440 women, was diagnosed between January 1, 1980 and December 31, 1999 in study townships. Patients from the endemic area had higher proportions of squamous cell and small cell carcinomas, but a lower proportion of adenocarcinomas. These findings were similar across all age groups in both genders, although the lack of data on smoking is a limitation of our study. The results suggested that the carcinogenicity of arsenic on lungs is also cell type-specific: squamous cell and small cell carcinomas appeared to be related to arsenic ingestion, but not adenocarcinoma. Whereas data in the literature are limited, the association between adenocarcinoma and arsenic exposures through inhalation appeared to be stronger than that of squamous cell carcinoma. Therefore, we speculate that arsenic may give rise to different mechanisms in the development of lung cancers through different exposure routes.
Inverse Association between Nonsteroidal Anti-inflammatory Drugs and Prostate Cancer
Authors: Garcı́a Rodrı́guez Luis A. , González-Pérez Antonio
Published: June 2022

Background: Prostate cancer is considered a major health problem in western countries. Promising results from observational studies on cancer at other sites fuelled the publication of several studies assessing the association between nonsteroidal anti-inflammatory drug (NSAID) use and prostate cancer. However, these studies show conflicting results. Methods: We conducted a cohort study with a nested case-control analysis to further study the association between NSAIDs and prostate cancer. We used data from the General Practice Research Database in United Kingdom. Results: Aspirin use was associated with a reduced risk of prostate cancer [odds ratio (OR) = 0.70, 95% confidence interval (95% CI) = 0.61–0.79]. We also found that paracetamol use with a treatment duration longer than 1 year was associated with a decreased risk (OR = 0.65, 95% CI = 0.54–0.78). Non-aspirin-NSAID (NA-NSAID) and paracetamol short-term use was associated with a small increased risk whereas long-term users of NA-NSAIDs presented an OR of 0.89 (95% CI = 0.73–1.08). Discussion: Our findings support a protective effect of aspirin and paracetamol against prostate cancer. The transient elevated risk observed among newly started users of NA-NSAIDs and paracetamol is most likely explained by prothopathic bias. We found some suggestion of a reduced risk with long-term use of NA-NSAID.
Family History and Environmental Risk Factors for Colon Cancer
Authors: Fernandez Esteve , Gallus Silvano , La Vecchia Carlo , Talamini Renato , Negri Eva , Franceschi Silvia
Published: June 2022

Background: We analyzed the joint effect of environmental risk factors and family history of colorectal cancer on colon cancer. Methods: We used data from a case-control study conducted in northern Italy between 1992 and 1996 including 1225 cases with colon cancer and 4154 controls. We created a weighed risk factor score for the main environmental risk factors in this population (positive family history, high education, low occupational physical activity, high daily meal frequency, low intake of fiber, low intake of calcium, and low intake of β-carotene). Results: Compared with the reference category (subjects with no family history of colorectal cancer and in the lowest tertile of the risk factor score), the odds ratios of colon cancer were 2.27 [95% confidence interval (CI) = 1.89–2.73] for subjects without family history and in the highest environmental risk factor score, 3.20 (95% CI = 2.05–5.01) for those with family history and low risk factor score, and 7.08 (95% CI = 4.68–10.71) for those with family history and high risk factor score. The pattern of risk was similar for men and women and no meaningful differences emerged according to subsite within the colon. Conclusions: Family history of colorectal cancer interacts with environmental risk factors of colon cancer.
Single-Dose Pharmacokinetic Study of Lycopene Delivered in a Well-Defined Food-Based Lycopene Delivery System (Tomato Paste-Oil Mixture) in Healthy Adult Male Subjects
Authors: Gustin David M. , Rodvold Keith A. , Sosman Jeffery A. , Diwadkar-Navsariwala Veda , Stacewicz-Sapuntzakis Maria , Viana Marlos , Crowell James A. , Murray Judith , Tiller Patricia , Bowen Phyllis E.
Published: June 2022

This report details the findings of a single-dose Phase I pharmacokinetic and toxicity study of a food-based formulation of lycopene in healthy adult male subjects. Five dosing groups (n = 5 per group) were sequentially treated with increasing doses of lycopene ranging from 10 to 120 mg. Blood samples were collected for a total of 28 days (672 h) after administration of single doses of lycopene. The mean time (tmax) to reach maximum total lycopene concentration (Cmax) ranged from 15.6 to 32.6 h. The Cmax for total lycopene ranged between 4.03 and 11.27 μg/dl (0.075–0.210 μm). Mean AUC0–96 and elimination half-life for total lycopene ranged from 214 to 655 μg h/dl (3.986–12.201 μmol h/l) and 28.1 and 61.6 h, respectively. The changes observed in lycopene exposure parameters (e.g., Cmax and AUC0–96) were not proportional to increments in dose, with larger increases observed at the lowest end of the dosing range (10–30 mg). Chylomicron lycopene was measured during the first 12 h with the differences observed among the dosing groups not reaching statistical significance. These findings may reflect a process of absorption that is saturable at very low dosing levels or may be explained by the large interindividual variability in attained lycopene concentrations that were observed within each dosing group. Pharmacokinetic parameters for trans- and cis-lycopene isomers were calculated and are reported here. The formulation was well tolerated with minimal side effects, which were mainly of gastrointestinal nature and of very low grade.
Lung Cancer Mortality Is Related to Age in Addition to Duration and Intensity of Cigarette Smoking: An Analysis of CPS-I Data
Authors: Knoke James D. , Shanks Thomas G. , Vaughn Jerry W. , Thun Michael J. , Burns David M.
Published: June 2022

Objectives: Models previously developed for predicting lung cancer mortality from cigarette smoking intensity and duration based on aggregated prospective mortality data have employed a study of British doctors and have assumed a uniform age of initiation of smoking. We reexamined these models using the American Cancer Society's Cancer Prevention Study I data that include a range of ages of initiation to assess the importance of an additional term for age. Methods: Model parameters were estimated by maximum likelihood, and model fit was assessed by residual analysis, likelihood ratio tests, and χ2 goodness-of-fit tests. Results: Examination of the residuals of a model proposed by Doll and Peto with the Cancer Prevention Study I data suggested that a better fitting model might be obtained by including an additional term specifying the ages when smoking exposure occurred. An extended model with terms for cigarettes smoked per day, duration of smoking, and attained age was found to fit statistically significantly better than the Doll and Peto model (P < 0.001) and to fit well in an absolute sense (goodness-of-fit; P = 0.34). Finally, a model proposed by Moolgavkar was examined and found not to fit as well as the extended model, although it included similar terms (goodness-of-fit; P = 0.007). Conclusions: The addition of age, or another measure of the timing of the exposure to smoking, improves the prediction of lung cancer mortality with Doll and Peto's multiplicative power model.
Diet-Induced Obesity Disrupts Histamine-Dependent Oleoylethanolamide Signaling in the Mouse Liver
Authors: Lin Lin , Mabou Tagne Alex , Squire Erica N. , Lee Hye-Lim , Fotio Yannick , Ramirez Jade , Zheng Mimi , Torrens Alexa , Ahmed Faizy , Ramos Raul , Plikus Maksim V. , Piomelli Daniele
Published: June 2022

Introduction: Previous work suggests the existence of a paracrine signaling mechanism in which histamine released from visceral mast cells into the portal circulation contributes to fasting-induced ketogenesis by stimulating biosynthesis of the endogenous high-affinity PPAR-α agonist oleoylethanolamide (OEA). Methods: Male C57Bl/6J mice were rendered obese by exposure to a high-fat diet (HFD; 60% fat). We measured histamine, OEA, and other fatty-acid ethanolamides by liquid-chromatography/mass spectrometry, gene transcription by RT-PCR, protein expression by ELISA, neutral lipid accumulation in the liver using Red Oil O and BODIPY staining, and collagen levels using picrosirius red staining. Results: Long-term exposure to HFD suppressed both fasting-induced histamine release into portal blood and histamine-dependent OEA production in the liver. Additionally, subchronic OEA administration reduced lipid accumulation, inflammatory responses, and fibrosis in the liver of HFD-exposed mice. Discussion: The results suggest that disruption of histamine-dependent OEA signaling in the liver might contribute to pathology in obesity-associated liver steatosis.
Combination of Mirogabalin and Duloxetine Attenuates Peripheral Neuropathy by Eribulin: A Novel Case Report
Authors: Saito Yoshitaka , Takekuma Yoh , Oshino Tomohiro , Sugawara Mitsuru
Published: June 2022

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most severe complications associated with chemotherapy for breast cancer. We encountered a case in which mirogabalin initially ameliorated, and additional duloxetine further attenuated eribulin-induced CIPN. Herein, we report its management. A 53-year-old woman received eribulin treatment as third-line chemotherapy for recurrent breast cancer. She experienced grade 2 CIPN with adjuvant docetaxel and cyclophosphamide treatment (worst numeric rating scale (NRS) 6/10 for numbness and 6/10 for pain) and had baseline grade 1 symptoms only in the hands (NRS 1/10 for each). CIPN in the hands and feet worsened to NRS 3/10 on day 1 of cycle 4. Mirogabalin (5 mg twice daily) was initiated, resulting in stable symptoms for approximately 6 weeks with grade 1 somnolence and heaviness of the head. The dosage was increased with careful attention to adverse effects to 22.5 mg per day, and the NRS was reduced from 5/10 to 3/10 for numbness and from 8/10 to 5/10 for pain. We administered duloxetine 20 mg with domperidone (10 mg three times a day) for further pain attenuation on day 1 of cycle 15, decreasing the NRS to 1/10 for numbness and 3/10 for pain. Duloxetine was increased due to CIPN degradation (NRS 3/10 and 5/10), resulting in a significant pain attenuation to 1/10. As the CIPN-attenuating mechanisms of mirogabalin and duloxetine are different, we consider that the additive and synergetic effects of this combination affected the results. Combination therapy with these drugs may be a promising strategy.
Unusual Presentation of Bilateral Chylothorax and Chylous Ascites with Pancreatic Adenocarcinoma: A Case Report
Authors: Fangsaard Panisara , Puriwekin Jirapa , Phattraprayoon Nanthida , Ungtrakul Teerapat
Published: June 2022

Chylothorax is a lymphatic fluid, which is contained in the pleural cavity. Chylothorax has a typical milky white fluid appearance and is diagnosed by triglyceride concentrations >110 mg/dL. The combination of chylothorax with chylous ascites is a rare condition that is difficult to manage. We present a case of a 60-year-old man who presented with dyspnea for 1 week and generalized abdominal distention. He was diagnosed with advanced-stage pancreatic adenocarcinoma and received palliative chemotherapy. On follow-up examination, he showed decreased breathing sounds in both lungs and marked ascites. Chest radiography showed bilateral pleural effusion, which was more prominent in the left hemithorax than the right hemithorax. Thoracocentesis and abdominal paracentesis were performed, and the finding of pleural and ascites fluid was compatible with bilateral chylothorax and chylous ascites. Although the patient was receiving dietary modification, he still required repeated thoracentesis. Bilateral chest tube insertion with medical pleurodesis with talc successfully treated his chylothorax. This treatment should be considered as an option for malignancy-associated chylothorax besides systemic cancer treatment to improve patients’ quality of life.
Membranous Nephropathy-Like Apolipoprotein E Deposition Disease with Apolipoprotein E Toyonaka and Homozygous Apolipoprotein E2/2 without Dyslipidemia, with Characteristic Electron-Dense Deposits
Authors: Koshino Akihiko , Takaeda Chikako , Matsuno Takahiro , Kitajima Shinji , Iwata Yasunori , Sakai Norihiko , Nagahama Kiyotaka , Niida Yo , Saito Takao , Yokoyama Hitoshi , Wada Takashi
Published: June 2022

Recently, several cases of novel apolipoprotein E (apoE)-related glomerular disease known as membranous nephropathy (MN)-like apoE deposition disease with apoE Toyonaka (Ser197Cys) and homozygous apoE2/2 have been reported. However, the clinical and pathological characteristics are uncertain due to the small number of reports. Here, we report an additional case with various clinical and pathological characteristics. A 28-year-old Japanese man with mild proteinuria and hematuria underwent a kidney biopsy. Examination under a light microscope revealed mesangial proliferation, mesangial matrix expansion, and segmental spike lesion. An immunofluorescence study showed no immunoglobulin or complement depositions. In the electron microscopic (EM) examination, massive deposits with various electron densities in the subepithelial, subendothelial, and paramesangial areas were more prominent than those reported in previous cases, which resembled microbubbles or microcysts on higher magnification. The glomerular basement membrane (GBM) structure was partly degenerated by these deposits. Serum triglyceride and cholesterol levels were within the normal range. However, the serum apoE concentration was significantly high, and glomerular apoE accumulation was detected in immunohistochemistry. The DNA sequence revealed apoE Toyonaka and homozygous apoE2/2 similar to that of the previous cases with MN-like apoE deposition disease. MN-like apoE deposition disease can manifest as only mild hematuria and proteinuria without dyslipidemia. Various characteristic deposits associated with GBM degeneration can be observed in the EM study.
Adoptively Transferred in vitro-Generated Myeloid-Derived Suppressor Cells Improve T-Cell Function and Antigen-Specific Immunity after Traumatic Lung Injury
Authors: Kustermann Monika , Dasari Prasad , Knape Ingrid , Keltsch Emma , Liu Jianing , Pflüger Silvia , Osen Wolfram , Holzmann Karlheinz , Huber-Lang Markus , Debatin Klaus-Michael , Strauss Gudrun
Published: June 2022

Immune reactions after trauma are characterized by immediate activation of innate immunity and simultaneously downregulation of adaptive immunity leading to a misbalanced immunohomeostasis and immunosuppression of the injured host. Therefore, the susceptibility to secondary infections is strongly increased after trauma. Immune responses are regulated by a network of immune cells influencing each other and at the same time modifying their functions dependent on the inflammatory environment. Although myeloid-derived suppressor cells (MDSCs) are initially described as T-cell suppressors, their immunomodulatory capacity after trauma is mostly undefined. Therefore, in vitro-generated MDSCs were adoptively transferred into mice after blunt chest trauma (TxT). A single MDSC treatment-induced splenic T-cell expansion decreased apoptosis sensitivity and improved proliferation in the absence of T-cell exhaustion until 2 weeks after trauma. MDSC treatment had a long-lasting effect on the genomic landscape of CD4+ T cells by upregulating primarily Th2-associated genes. Remarkably, immune-activating functions of MDSCs supported the ability of TxT mice to respond to post-traumatic secondary antigen challenge. Secondary insults were mimicked by immunizing MDSC-treated TxT mice with ovalbumin (OVA), followed by OVA restimulation in vitro. MDSC treatment significantly increased the frequency of OVA-specific T cells, enhanced their Th1/Th2 cytokine expression, and induced upregulation of cytolytic molecules finally improving OVA-specific cytotoxicity. Overall, we could show that therapeutic MDSC treatment after TxT improves post-traumatic T-cell functions, which might enable the traumatic host to counterbalance trauma-induced immunoparalysis.
Metastasiertes malignes Melanom: Neue Kombinationstherapie bietet weitere wirkungsvolle Option
Authors: Schlaak Max
Published: June 2022

Die globale, doppelblinde, randomisierte RELATIVITY-047-Studie untersuchte die Kombination aus Relatlimab und Nivolumab im Vergleich zu Nivolumab allein für Patient*innen mit unbehandeltem metastasiertem oder inoperablem Melanom. Der primäre Endpunkt war das progressionsfreie Überleben. Das mediane progressionsfreie Überleben betrug 10,1 Monate (95% Konfidenzintervall [KI], 6,4 bis 15,7) mit Relatlimab-Nivolumab im Vergleich zu 4,6 Monaten (95% KI, 3,4 bis 5,6) mit Nivolumab (Hazard Ratio für Progression oder Tod, 0,75 [95% KI, 0, 62 bis 0, 92]; P = 0,006 durch den Log-Rank-Test). Das progressionsfreie Überleben nach 12 Monaten betrug 47,7% (95% KI, 41,8 bis 53,2) mit Relatlimab-Nivolumab im Vergleich zu 36,0% (95% KI, 30,5 bis 41,6) mit Nivolumab. Unerwünschte Ereignisse in Folge der Behandlung des Grades 3 oder 4 traten bei 18,9% der Patienten in der Relatlimab-Nivolumab-Gruppe und bei 9,7% der Patienten in der Nivolumab-Gruppe auf. Die Autoren der Studie stellen fest, dass die Hemmung von zwei Immun-Checkpoints, LAG-3 und PD-1, einen größeren Nutzen in Bezug auf das progressionsfreie Überleben als die Hemmung von PD-1 allein bei Patienten mit zuvor unbehandeltem metastasiertem oder inoperablem Melanom erbrachte.
Thrombolysis for Acute Ischemic Stroke in Patients With Premorbid Disability: A Meta-Analysis
Authors: Beland Benjamin , Bala Fouzi , Ganesh Aravind
Published: June 2022

Background:

Randomized controlled trials for the use of alteplase in acute ischemic stroke have excluded or had little representation of patients with prestroke disability, and the benefit of alteplase in this population remains uncertain. We performed a systematic review and meta-analysis to examine the outcomes of thrombolysis in patients with premorbid disability.

Methods:

We performed a systematic review in accordance with the Meta-Analysis of Observational Studies in Epidemiology guidelines and retrieved studies reporting intravenous thrombolysis (IVT) in patients with prestroke disability (modified Rankin Scale score, 3–5) with acute ischemic stroke, either compared with untreated patients or treated patients without premorbid disability. The primary outcome was the return to premorbid disability at 90 days. Secondary outcomes included rate and odds ratio of favorable functional outcome at 90 days (modified Rankin Scale score 0–2 or return to premorbid modified Rankin Scale), symptomatic intracerebral hemorrhage (sICH), and 90-day mortality.

Results:

Eight articles were included involving 103 988 patients. Patients with disability treated with IVT had better odds of returning to baseline function compared with those who did not receive IVT (odds ratio, 7.26 [95% CI, 2.51–21.02]). Mortality and rates of sICH were not significantly different between patients with disability treated with IVT and those not treated, although there were numerically more sICHs in the IVT group. Return to baseline function was not significantly different between patients with and without prestroke disability (odds ratio, 1.46 [95% CI, 0.75–2.83]). The rates of sICH were not significantly different in patients with and without premorbid disability. However, mortality was 3× higher in patients with premorbid disability than in those without premorbid disability (38.2% versus 12.6%).

Conclusions:

The use of IVT in patients with disability was associated with better outcomes compared with patients who did not receive IVT without statistically significant added risks of sICH or mortality. When compared with those without disability, there was no significant difference in the return to baseline function or sICH. High-quality data comparing treated versus untreated patients with premorbid disability are needed to clarify this issue.

Registration:

URL:
https://www.crd.york.ac.uk/PROSPERO/
; Unique identifier: CRD42021240499.
Structural white matter characteristics for working memory and switching/inhibition in children with reading difficulties: The role of the left superior longitudinal fasciculus
Authors: Farah Rola , Glukhovsky Noam , Rosch Keri , Horowitz-Kraus Tzipi
Published: June 2022

Reading difficulties (RDs) are characterized by slow and inaccurate reading as well as additional challenges in cognitive control (i.e., executive functions, especially in working memory, inhibition, and visual attention). Despite evidence demonstrating differences in these readers’ language and visual processing abilities, white matter differences associated with executive functions (EFs) difficulties in children with RDs are scarce. Structural correlates for reading and EFs in 8- to 12-year-old children with RDs versus typical readers (TRs) were examined using diffusion tensor imaging (DTI) data. Results suggest that children with RDs showed significantly lower reading and EF abilities versus TRs. Lower fractional anisotropy (FA) in left temporo-parietal tracts was found in children with RDs, who also showed positive correlations between reading and working memory and switching/inhibition scores and FA in the left superior longitudinal fasciculus (SLF). FA in the left SLF predicted working memory performance mediated by reading ability in children with RDs but not TRs. Our findings support alterations in white matter tracts related to working memory, switching/inhibition, and overall EF challenges in children with RDs and the linkage between working memory difficulties and FA alterations in the left SLF in children with RDs via reading.
Caught in the Crossfire between Being a Woman and Being a Refugee
Authors: Bergoffen Debra
Published: June 2022

Two crises of our age, refugee statelessness and sexual violence, converge in the lives of refugee women. This article examines this convergence by analyzing the meanings of refugee-camp sexual aggression and refugee women’s responses to it. Aligning Giorgio Agamben’s and Hannah Arendt’s ideas of refugee desubjectification with Simone de Beauvoir’s concept of gendered subjectivity, the author argues that refugee-camp men use sexual violence to reinstate their gendered subjectivity. In rejecting men’s demand that women accept their prerefugee, compromised subjectivity, refugee-camp women are rewriting the gendered subjectivity contract.