bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glycemic Index, Glycemic Load, and Carbohydrate Intake in Relation to Risk of Distal Colorectal Adenoma in Women
Authors: Oh Kyungwon , Willett Walter C. , Fuchs Charles S. , Giovannucci Edward L. 
Published: June 2022

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

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

Abstract
Objective: Controversy remains regarding the association between type 2 diabetes mellitus (DM) and colorectal cancer (CRC) risk. To clarify and extend the existing data, we prospectively evaluated the association between self-reported type 2 DM (onset at &gt;30 years of age) and incident CRC, overall and by anatomic subsite, among postmenopausal women in the Iowa Women's Health Study (n = 35,230).
Methods: After 14 years of follow-up, a total of 870 incident CRC cases were identified through annual linkage to the Iowa Cancer Registry. DM was analyzed as reported at baseline and as a time-dependent variable using information obtained during follow-up. CRC risks were estimated using Cox proportional hazards regression models.
Results: After adjusting for age, body mass index and other potential confounding variables, the relative risk (RR) for women with DM versus women without DM was modestly increased at 1.4 [95% confidence interval (95% CI), 1.1-1.8]. By anatomic subsite, the RR for proximal colon cancer was statistically significantly increased (RR, 1.9; 95% CI, 1.3-2.6), whereas the RRs for distal colon (RR, 1.1; 95% CI, 0.6-1.8) and rectal cancer (RR, 0.8; 95% CI, 0.4-1.6) were not statistically different from unity. Analyses that included DM ascertained at baseline and follow-up yielded similar results.
Conclusion: In this large, prospective study of postmenopausal women, the association between DM and incident CRC was found to be subsite specific. If confirmed by others, this finding implies that CRC prevention strategies among type 2 DM patients should include examination of the proximal colon.
Cytochrome P450 1A1 Polymorphism and Childhood Leukemia: An Analysis of Matched Pairs Case-Control Genotype Data
Authors: Selvin Steve 
Published: June 2022

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

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

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

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

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

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

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

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

Abstract
Objective: The evidence for the effectiveness of screening is strongest for women ages 50 to 69 years; however, there is variation in the target age group for screening programs between different countries. In particular, there is uncertainty over whether women should continue screening once they reach age 70. We therefore investigated incidence rates for invasive and in situ breast cancer by age as well as prognostic features of tumors within a screening program. Methods: We studied 474,808 women who attended BreastScreen Victoria from January 1, 1993 to December 31, 2000. Of these women, 5,301 were diagnosed with invasive cancer and 1,127 were diagnosed with ductal carcinoma in situ. We used generalized additive models to model age-incidence rates for invasive cancers and ductal carcinoma in situ separately by users and nonusers of hormone replacement therapy at most recent screen. Nonparametric trends for ordered groups and regression methods were used to investigate trends in size, grade, and nodal involvement for invasive tumors by type of attendance and time since previous negative screen for age group. Results: The incidence of ductal carcinoma in situ among women with a previous negative screen clearly declined after age 70 irrespective of hormone replacement therapy use. At subsequent screen, the age-incidence curve for invasive breast cancer flattened at ages 60 to 75 years and then increased only for women taking hormone replacement therapy. Tumor size at diagnosis declined with age at both first round (P = 0.15) and subsequent round (P = 0.08). The proportion of poorly differentiated tumors also decreased with age, with the smallest proportion of grade III tumors diagnosed in women ages ≥75 years (P = 0.09 for first screen and P = 0.05 for subsequent screen). The presence of positive nodes at diagnosis declined with age (P &lt; 0.001) for both first and subsequent screening rounds. Conclusion: Older age is associated with more favorable prognostic tumor features and a lower incidence of ductal carcinoma in situ among subsequent attenders of screening. When making decisions regarding continuing screening, older women and their physicians should also consider the presence of other comorbid conditions that may mitigate any impact of screening on mortality.