bluuebunny/crossref_metadata_2025 huggingface dataset:
Soluble Epidermal Growth Factor Receptor (SEG-FR) and Cancer Antigen 125 (CA125) as Screening and Diagnostic Tests for Epithelial Ovarian Cancer
Authors: Baron Andre T. , Boardman Cecelia H. , Lafky Jacqueline M. , Rademaker Alfred , Liu Dachao , Fishman David A. , Podratz Karl C. , Maihle Nita J.
Published: September 2005

Epithelial ovarian cancer (EOC) is the leading cause of death among all gynecologic cancers in the United States. Because women who are diagnosed with early stage disease have a better prognosis than women diagnosed with late stage disease, early detection represents a potentially practical approach to reduce the mortality associated with EOC. Unfortunately, no single screening test has proven to be effective for this purpose, and a valid and feasible screening program to detect early stage EOC in the general population has not yet been devised. Consequently, research has focused on coupling two or more screening modalities to improve program validity and feasibility. Serum cancer antigen 125 (CA125) and a soluble isoform of the epidermal growth factor receptor (p110 sEGFR) have been studied individually as biomarkers of ovarian cancer. In this study, we compare serum CA125 levels and sEGFR concentrations in women with EOC to women with benign gynecologic conditions of ovarian and non-ovarian origin. We show that serum sEGFR concentrations are lower in patients with EOC than in women with benign gynecologic conditions, whereas serum CA125 levels are higher in patients to EOC compared with women with benign gynecologic conditions. These data also reveal that age and serum sEGFR concentrations modify the association between CA125 levels and EOC versus benign gynecologic disease. Hence, age- and sEGFR-dependent CA125 cutoff thresholds improve the ability of CA125 to discern EOC patients from women with benign ovarian tumors and non-ovarian gynecologic conditions. Our analyses show that parallel testing with fixed sEGFR and CA125 cutoff thresholds optimizes sensitivity to detect EOC, whereas serial testing with age- and sEGFR-dependent CA125 cutoff thresholds optimizes test specificity, and overall accuracy to discern patients with EOC from women with benign ovarian and non-ovarian gynecologic conditions. The combined use of serologic sEGFR and CA125, thus, has improved utility for screening and diagnosing EOC, which may increase the positive predictive value of a multimodal screening program that incorporates these biomarkers to detect and subsequently differentiate benign from malignant ovarian tumors.
Fruit and Vegetable Intake during Pregnancy and Risk for Development of Sporadic Retinoblastoma
Authors: Orjuela Manuela A. , Titievsky Lina , Liu Xinhua , Ramirez-Ortiz Marco , Ponce-Castaneda Veronica , Lecona Evelia , Molina Evelyn , Beaverson Katherine , Abramson David H. , Mueller Nancy E.
Published: September 2005

Objective: Little is known about the causes of sporadic (noninherited) retinoblastoma. Rates seem to be somewhat higher among poorer populations in Mexico. Fruits and vegetables are important sources of carotenoids and folate. We examined whether decreased gestational maternal intake of fruits and vegetables may contribute to development of sporadic retinoblastoma.

Methods: At the Instituto Nacional de Pediatria in Mexico City, we conducted a hospital-based case-control study to evaluate prenatal maternal diet. We examined dietary intake of fruits and vegetables of mothers of 101 children with retinoblastoma and 172 control children using a dietary recall questionnaire and published food nutrient content tables.

Results: The reported number of mean daily servings of fruits and vegetables was lower among case mothers when compared with control mothers [vegetables: 2.28 in controls, 1.75 in cases (P < 0.01); fruits: 2.13 in controls, 1.59 in cases (P = 0.07)]. Mean daily maternal folate intake from both vegetables and fruits was higher in controls (103 μg) than in cases (48 μg; P < 0.05). Risk for having a child with retinoblastoma was increased for mothers consuming fewer than 2 daily servings of vegetables [odds ratios (OR), 3.4; 95% confidence interval (95% CI), 2.0-6.0] or with a low intake of folate (OR, 3.9; 95% CI, 2.1, 7.3), or lutein/zeaxanthin (OR, 2.6; 95% CI, 1.5-4.6) derived from fruits and vegetables.

Conclusions: Decreased intake of vegetables and fruits during pregnancy and the consequent decreased intake of nutrients such as folate and lutein/zeaxanthin, necessary for DNA methylation, synthesis, and retinal function, may increase risk for having a child with sporadic retinoblastoma.
A Urinary Metabolite of Phenanthrene as a Biomarker of Polycyclic Aromatic Hydrocarbon Metabolic Activation in Workers Exposed to Residual Oil Fly Ash
Authors: Kim Jee Young , Hecht Stephen S. , Mukherjee Sutapa , Carmella Steven G. , Rodrigues Ema G. , Christiani David C.
Published: September 2005

Residual oil fly ash is a chemically complex combustion product containing a significant component of potentially carcinogenic transition metals and polycyclic aromatic hydrocarbons (PAH). Various biomarkers of PAH exposure have been investigated previously, most notably 1-hydroxypyrene (1-OHP), in urine. In this study, we assessed the utility of r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (trans, anti-PheT), a metabolite of phenanthrene, to detect occupational PAH exposure. Urine samples collected across the workweek were analyzed for 1-OHP and trans, anti-PheT in boilermakers (n = 20) exposed to residual oil fly ash. Median baseline urinary trans, anti-PheT concentrations were 0.50 μg/g creatinine in current tobacco smokers and 0.39 μg/g creatinine in nonsmokers. Median baseline urinary 1-OHP concentrations in smokers and nonsmokers were 0.31 and 0.13 μg/g creatinine, respectively. To study further the effect of smoking exposure on the urinary PAH markers, urinary cotinine was used. Although urinary trans, anti-PheT and 1-OHP concentrations were correlated (Spearman r = 0.63; P < 0.001) for all subjects, the regression coefficient between log-transformed trans, anti-PheT and log 1-OHP was statistically significant only for subjects with low levels of urinary cotinine or for nonsmokers. Each 1-unit increase in log 1-OHP was associated with a 0.77-unit increase (95% confidence interval, 0.45-1.09) in log trans, anti-PheT in subjects with low levels of urinary cotinine (P < 0.001). In these subjects, dichotomized occupational exposure status was a significant predictor of log trans, anti-PheT (P = 0.02) but not of log 1-OHP (P = 0.2). In conclusion, we found that urinary trans, anti-PheT was detected in levels comparable with 1-OHP in occupationally exposed workers, particularly nonsmokers. This study shows that urinary trans, anti-PheT may be an effective biomarker of uptake and metabolic activation of PAHs.
Dietary Factors and Risk of Non-Hodgkin Lymphoma in Men and Women
Authors: Chang Ellen T. , Ekström Smedby Karin , Zhang Shumin M. , Hjalgrim Henrik , Melbye Mads , Öst Åke , Glimelius Bengt , Wolk Alicja , Adami Hans-Olov
Published: September 2005

Background: The incidence of non-Hodgkin lymphoma (NHL) has increased worldwide in recent decades. Diet could influence NHL risk by modulating the immune system, although evidence is limited. We did a population-based case-control study to determine whether differences in diet were associated with NHL risk.

Methods: A total of 597 NHL cases and 467 population controls in Sweden completed a semiquantitative food frequency questionnaire evaluating their dietary habits 2 years before the interview. Unconditional logistic regression was used to estimate the odds ratios (OR) and corresponding 95% confidence intervals (95% CI) for associations between food intake and risk of NHL.

Results: High consumption of dairy products and fried red meat was associated with increased risk of NHL. The OR of NHL for individuals in the highest quartile compared with the lowest quartile of dairy intake was 1.5 (95% CI, 1.1-2.2; Ptrend = 0.003). The OR for the highest versus lowest quartile of fried red meat intake was 1.5 (95% CI, 1.0-2.1; Ptrend = 0.02). In contrast, high consumption of fruits and vegetables was associated with reduced risk of NHL, particularly follicular lymphoma, among women but not men. Compared with the lowest quartile of vegetable intake, the OR of follicular lymphoma among women in the highest quartile of vegetable intake was 0.3 (95% CI, 0.1-0.7; Ptrend = 0.002).

Conclusions: The positive associations of NHL risk with dairy products and fried red meat and the inverse association with fruits and vegetables suggest that diet affects NHL risk and could explain the increase of some histopathogic subtypes.
Prediagnostic Plasma Vascular Endothelial Growth Factor Levels and Risk of Prostate Cancer
Authors: Li Haojie , Kantoff Philip W. , Ma Jing , Stampfer Meir J. , George Daniel J.
Published: September 2005

Vascular endothelial growth factor (VEGF) plays important roles in endothelial cell proliferation, vascular permeability, and angiogenesis that may be critical to prostatic carcinogenesis and progression. Plasma VEGF levels were significantly greater in patients with metastatic prostate cancer compared with those with localized disease or healthy controls, and plasma VEGF level at prostate cancer diagnosis was an independent prognostic marker for survival in patients with hormone refractory prostate cancer. We therefore examined the association between prediagnostic plasma VEGF levels and risk of prostate cancer and disease phenotype. Using plasma samples obtained in 1982 from healthy men enrolled in the Physicians' Health Study, we conducted a nested case-control study among 504 men diagnosed with prostate cancer during 13 years of follow-up and 520 controls. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using multivariate logistic regression. Prediagnostic plasma VEGF levels were similar among cases and controls. Plasma VEGF concentration was not associated with subsequent risk of prostate cancer (third versus first tertile OR, 1.09; 95% CI, 0.80-1.49; Ptrend = 0.65). Furthermore, no association was observed among men with advanced (stage C or D) prostate cancer or among those who died of prostate cancer. Our results indicate that prediagnostic circulating VEGF levels are not associated with prostate cancer development and have limited value in predicting future risk of prostate cancer.
Postmenopausal Breast Cancer Risk and Cumulative Number of Menstrual Cycles
Authors: Chavez-MacGregor Mariana , Elias Sjoerd G. , Onland-Moret N. Charlotte , van der Schouw Yvonne T. , Van Gils Carla H. , Monninkhof Evelyn , Grobbee Diederick E. , Peeters Petra H.M.
Published: September 2005

Objective: To explore whether the lifetime cumulative number of menstrual cycles, as an index for total exposure to endogenous estrogens, and the number of menstrual cycles until a first full-term pregnancy (FFTP), are associated with breast cancer risk in postmenopausal women.

Methods: Population-based study with data from the Prospect-European Prospective Investigation into Cancer and Nutrition study. Naturally menopausal participants were eligible (n = 6,718). The cumulative number of menstrual cycles was computed in 6,031 (90%) women. We calculated the number of cycles until FFTP among parous participants. The number of menstrual cycles was impossible to compute in women who reported to be always irregular; therefore, we added the “always irregular” category in the analysis. During the 46,746 person-years of follow-up, 168 breast cancer cases were identified. Cox regression models were used and adjustments were made to account for potential confounders.

Results: Even when our data does not show a clear linear gradient, we observed an increased breast cancer risk in women with a higher number of cumulative menstrual cycles in their lifetime. Using ≤415 cycles as reference, the hazard ratio for the irregular group, 416-453, 454-490, and ≥491 cycles was 1.11 (.56, 2.19), 1.88 (1.14, 3.12), 1.74 (1.05, 2.87), and 1.80 (1.09, 2.96), respectively. Although not statistically significant, and of less magnitude, the risk estimates for the number of cycles before FFTP showed the same tendency.

Conclusion: Among women who underwent natural menopause, a higher number of menstrual cycles in lifetime, reflecting a longer exposure to endogenous estrogens, is associated with an increased breast cancer risk.
Vascular Endothelial Growth Factor Gene Polymorphisms and Risk of Primary Lung Cancer
Authors: Lee Su Jeong , Lee Sin Yeob , Jeon Hyo-Sung , Park Sun Ha , Jang Jin Sung , Lee Ga Young , Son Ji Woong , Kim Chang Ho , Lee Won Kee , Kam Sin , Park Rang Woon , Park Tae-In , Kang Young Mo , Kim In-San , Jung Tae Hoon , Park Jae Yong
Published: September 2005

Angiogenesis is an essential process in the development, growth, and metastasis of malignant tumors including lung cancer. DNA sequence variations in the vascular endothelial growth factor (VEGF) gene may lead to altered VEGF production and/or activity, thereby causing interindividual differences in the susceptibility to lung cancer via their actions on the pathways of tumor angiogenesis. To test this hypothesis, we investigated the potential association between three VEGF polymorphisms (−460T > C, +405C > G, and 936C > T)/haplotypes and the risk of lung cancer in a Korean population. VEGF genotypes were determined in 432 lung cancer patients and 432 healthy controls that were frequency matched for age and sex. VEGF haplotypes were predicted using Bayesian algorithm in the phase program. Compared with the combined +405 CC and CG genotype, the +405 GG genotype found associated with a significantly decreased risk of small cell carcinoma [SCC; adjusted odds ratio (OR), 0.36; 95% confidence interval (95% CI), 0.17-0.78]. The 936 CT genotype and the combined 936 CT and TT genotype were also associated with a significantly decreased risk of SCC compared with the 936 CC genotype (adjusted OR, 0.47; 95% CI, 0.26-0.85 and adjusted OR, 0.44; 95% CI, 0.24-0.80, respectively). Haplotype CGT was associated with a significantly decreased risk of SCC (adjusted OR, 0.39; 95% CI, 0.18-0.87), whereas haplotype TCC conferred a significantly increased risk of SCC (adjusted OR, 1.63; 95% CI, 1.14-2.33). None of the VEGF polymorphisms studied significantly influenced the susceptibility to lung cancer except SCC. However, haplotypes TCT and TGT were significantly associated with the risk of overall lung cancer, respectively (adjusted OR, 0.38; 95% CI, 0.25-0.60 and adjusted OR, 3.94; 95% CI, 2.00-7.76, respectively). These effects of haplotypes TCT and TGT on lung cancer risk were observed in three major histologic types of lung cancer. These results suggest that the VEGF gene may be contribute to an inherited predisposition to lung cancer.
A Model-Based Comparison of Breast Cancer Screening Strategies: Mammograms and Clinical Breast Examinations
Authors: Shen Yu , Parmigiani Giovanni
Published: September 2005

In screening for secondary prevention of breast cancer, clinical breast examination (CBE) combined with mammography may improve overall screening sensitivity compared with mammography alone. A systematic evaluation of the relative expenses and projected benefit of combining these two screening modalities is not presently available. We addressed this issue using a microsimulation model incorporating age-specific preclinical duration of the disease, age-specific sensitivities of the two modalities, age-specific incidence of the disease, screening strategy, and competing causes of mortality. We examined a total of 48 screening strategies, depending on the age range, the examination interval, and whether mammography or CBE is given at every one or two exam. Our results indicate that a biennial mammography can be cost-effective if coupled with annual CBE. For each screening interval and starting age, giving mammography every two exams and CBE at every exam has the lowest marginal cost per year of quality-adjusted life saved, whereas giving both at every exam has the highest. Comparing annual mammography and CBE to biennial mammography and annual CBE from 50 to 79, the total cost was reduced by 35%, whereas the marginal quality-adjusted life years only decreased by 12%. Similar reductions are observed for other starting ages. It is cost-effective to have a biennial mammography if coupled with an annual CBE. Annual mammography combined with CBE every 6 months will lead to a 41% increase in the quality-adjusted life years compared with annual mammography and CBE from 50 to 79, whereas the total cost increases by 30%.
Risk Factors, DNA Damage, and Disease Progression in Barrett's Esophagus
Authors: Olliver Joanna R. , Hardie Laura J. , Gong YunYun , Dexter Simon , Chalmers Douglas , Harris Keith M. , Wild Christopher P.
Published: September 2005

Esophageal adenocarcinoma develops on a background of Barrett's esophagus. A number of risk factors have been linked to both conditions, including gastroesophageal reflux and smoking. However, the molecular mechanisms by which these factors influence disease progression remain unclear. One possibility is that risk factors generate promutagenic DNA damage in the esophagus. The comet assay was used to measure DNA damage in esophageal (Barrett's and squamous) and gastric mucosa of Barrett's patients with (n = 24) or without (n = 50) associated adenocarcinoma or high-grade dysplasia in comparison with control patients (squamous mucosa) without Barrett's esophagus (n = 64). Patients completed a questionnaire detailing exposure to some of the known risk factors for Barrett's esophagus and adenocarcinoma. In Barrett's esophagus patients, DNA damage was higher in Barrett's mucosa compared with normal esophageal and gastric mucosa (P < 0.001). In addition, the highest quartile of DNA damage in Barrett's mucosa was associated with an increased risk (odds ratio, 9.4; 95% confidence interval, 1.1-83.4; P = 0.044) of developing adenocarcinoma or high-grade dysplasia compared with DNA damage levels in the lowest quartile. Smoking was associated with higher DNA damage in squamous epithelium in all patient groups (P < 0.01) and in Barrett's mucosa (P < 0.05) in Barrett's esophagus patients only. In controls only, current reflux was associated with higher DNA damage, whereas anti-inflammatory drug use resulted in lower levels. Collectively, these data imply a genotoxic insult to the premalignant Barrett's mucosa that may explain the genetic instability in this tissue and the progression to adenocarcinoma. There is an indication for a role for smoking in inducing DNA damage in esophageal mucosa but an understanding of the role of reflux requires further investigation.
PTGS2 (COX-2) −765G > C Promoter Variant Reduces Risk of Colorectal Adenoma among Nonusers of Nonsteroidal Anti-inflammatory Drugs
Authors: Ulrich Cornelia M. , Whitton John , Yu Joon-Ho , Sibert Justin , Sparks Rachel , Potter John D. , Bigler Jeannette
Published: September 2005

Prostaglandin H synthase 2 (PTGS2) or cyclooxygenase-2 (COX-2) has been shown to play a key role in the regulation of inflammation, and its inhibition is associated with a reduced risk of colon cancer. The PTGS2 (COX-2) −765G > C promoter variant is located in a putative SP1 binding site and reduces PTGS2 expression. In a Minnesota-based case-control study of cases with adenomatous (n = 494) or hyperplastic polyps (n = 186) versus polyp-free controls (n = 584), we investigated the role of the PTGS2 −765G > C promoter polymorphism. Multiple logistic regression analysis was used, adjusting for age, body mass index, caloric intake, alcohol, fiber, sex, hormone use, and smoking. For colorectal adenoma, odds ratios (OR) compared with PTGS2 −765GG as reference were GC 1.00 [95% confidence interval (95% CI), 0.74-1.35] and CC 0.53 (95% CI, 0.22-1.28). For hyperplastic polyps, the comparable adjusted odds ratios were GC 0.97 (95% CI, 0.65-1.46) and CC 0.24 (95% CI, 0.05-1.11). Risk associated with the −765G > C variant differed by aspirin or other nonsteroidal anti-inflammatory drug (NSAID) use. Among nonusers of aspirin or other NSAIDs, the CC genotype conferred a significant decrease in risk of adenoma (OR, 0.26; 95% CI, 0.07-0.89). Use of aspirin or other NSAIDs reduced risk of adenoma only among those with the −765GG (wild type) and possibly −765CG genotypes (OR, 0.66; 95% CI, 0.48-0.92 and OR, 0.64; 95% CI, 0.40-1.02, respectively). These data suggest that COX-2 expression or activity may be beneficially suppressed, and risk of colorectal polyps reduced, by aspirin or other NSAIDs in PTGS2 −765GG (wild type) individuals and by the −765 CC variant genotype in nonusers of NSAIDs.
Geographic Patterns of Prostate Cancer Mortality and Variations in Access to Medical Care in the United States
Authors: Jemal Ahmedin , Ward Elizabeth , Wu Xiaocheng , Martin Howard J. , McLaughlin Colleen C. , Thun Michael J.
Published: September 2005

Background: Striking geographic variation in prostate cancer death rates have been observed in the United States since at least the 1950s; reasons for these variations are unknown. Here we examine the association between geographic variations in prostate cancer mortality and regional variations in access to medical care, as reflected by the incidence of late-stage disease, prostate-specific antigen (PSA) utilization, and residence in rural counties.

Methods: We analyzed mortality data from the National Center for Health Statistics, 1996 to 2000, and incidence data from 30 population-based central cancer registries from the North American Association of Central Cancer Registries, 1995 to 2000. Ecological data on the rate of PSA screening by registry area were obtained from the 2001 Behavioral Risk Factor Surveillance System. Counties were grouped into metro and nonmetro areas according to Beale codes from the Department of Agriculture. Pearson correlation analyses were used to examine associations.

Results: Significant correlations were observed between the incidence of late-stage prostate cancer and death rates for Whites (r = 0.38, P = 0.04) and Blacks (r = 0.53, P = 0.03). The variation in late-stage disease corresponded to about 14% of the variation in prostate cancer death rates in White men and 28% in Black men. PSA screening rate was positively associated with total prostate cancer incidence (r = 0.42, P = 0.02) but inversely associated with the incidence of late-stage disease (r = −0.58, P = 0.009) among White men. Nonmetro counties generally had higher death rates and incidence of late-stage disease and lower prevalence of PSA screening (53%) than metro areas (58%), despite lower overall incidence rates.

Conclusion: These ecological data suggest that 10% to 30% of the geographic variation in mortality rates may relate to variations in access to medical care.
Similar Uptake of Lung Carcinogens by Smokers of Regular, Light, and Ultralight Cigarettes
Authors: Hecht Stephen S. , Murphy Sharon E. , Carmella Steven G. , Li Shelby , Jensen Joni , Le Chap , Joseph Anne M. , Hatsukami Dorothy K.
Published: September 2005

Cigarette design has changed markedly over the past 60 years and sales-weighed levels of tar and nicotine have decreased. Currently, cigarettes are classified as regular (>14.5 mg tar), light (>6.5-14.5 mg tar), and ultralight (≤6.5 mg tar), based on a Federal Trade Commission–specified machine-smoking protocol. Epidemiologic studies suggest that there is no difference in lung cancer risk among people who smoke light or ultralight cigarettes compared with regular cigarettes, but the uptake of lung carcinogens in smokers of these types of cigarettes has never been reported. We recruited 175 smokers, who filled out a tobacco use questionnaire in which their current brand was identified as regular, light, or ultralight. Urine samples were collected and analyzed for 1-hydroxypyrene (1-HOP), total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL plus its glucuronides) and total cotinine (cotinine plus its glucuronides). 1-HOP and total NNAL are biomarkers of uptake of polycyclic aromatic hydrocarbons and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, lung carcinogens in cigarette smoke. Total cotinine is a biomarker of nicotine uptake. There were no statistically significant differences in urinary levels of 1-HOP, total NNAL, and total cotinine in smokers of regular, light, and ultralight cigarettes, whether the results were expressed per mg urinary creatinine, per mL of urine, or per mg creatinine divided by cigarettes per day. Levels of machine measured tar were available for the cigarettes smoked by 149 of the subjects. There was no correlation between levels of tar and any of the biomarkers. These results indicate that lung carcinogen and nicotine uptake, as measured by urinary 1-HOP, total NNAL, and total cotinine is the same in smokers of regular, light, and ultralight cigarettes. The results are consistent with epidemiologic studies that show no difference in lung cancer risk in smokers of these cigarettes.
Fiber Intake and Incidence of Colorectal Cancer among 76,947 Women and 47,279 Men
Authors: Michels Karin B. , Fuchs Charles S. , Giovannucci Edward , Colditz Graham A. , Hunter David J. , Stampfer Meir J. , Willett Walter C.
Published: September 2005

Prospective cohort studies have consistently found no important link between fiber intake and risk of colorectal cancer. The recent large, prospective European Prospective Investigation into Cancer and Nutrition has challenged this paradigm by suggesting significant protection by high fiber intake. We prospectively investigated the association of fiber intake with the incidence of colon and rectal cancers in two large cohorts: the Nurses' Health Study (76,947 women) and the Health Professionals Follow-up Study (47,279 men). Diet was assessed repeatedly in 1984, 1986, 1990, and 1994 among women and in 1986, 1990, and 1994 among men. The incidence of cancer of the colon and rectum was ascertained up to the year 2000. Relative risk estimates were calculated using a Cox proportional hazards model simultaneously controlling for potential confounding variables. During follow-up including 1.8 million person-years and 1,596 cases of colorectal cancer, we found little association with fiber intake after controlling for confounding variables. The hazard ratio for a 5-g/d increase in fiber intake was 0.91 (95% confidence interval, 0.87-0.95) after adjusting for covariates used in the European Prospective Investigation into Cancer and Nutrition study and 0.99 (95% confidence interval, 0.95-1.04) after adjusting for additional confounding variables. Our data from two large prospective cohorts with long follow-up and repeated assessment of fiber intake and of a large number of potential confounding variables do not indicate an important association between fiber intake and colorectal cancer but reveal considerable confounding by other dietary and lifestyle factors.
Human Papillomavirus Types in Head and Neck Squamous Cell Carcinomas Worldwide: A Systematic Review
Authors: Kreimer Aimee R. , Clifford Gary M. , Boyle Peter , Franceschi Silvia
Published: September 2005

Mucosal human papillomaviruses (HPV) are the cause of cervical cancer and likely a subset of head and neck squamous cell carcinomas (HNSCC), yet the global prevalence and type distribution of HPV in HNSCC remains unclear. We systematically reviewed published studies of HNSCC biopsies that employed PCR-based methods to detect and genotype HPV to describe the prevalence and type distribution of HPV by anatomic cancer site. Geographic location and study size were investigated as possible sources of variability. In the 5,046 HNSCC cancer specimens from 60 studies, the overall HPV prevalence was 25.9% [95% confidence interval (95% CI), 24.7-27.2]. HPV prevalence was significantly higher in oropharyngeal SCCs (35.6% of 969; 95% CI, 32.6-38.7) than oral SCCs (23.5% of 2,642; 95% CI, 21.9-25.1) or laryngeal SCCs (24.0% of 1,435; 95% CI, 21.8-26.3). HPV16 accounted for a larger majority of HPV-positive oropharyngeal SCCs (86.7%; 95% CI, 82.6-90.1) compared with HPV-positive oral SCCs (68.2%; 95% CI, 64.4-71.9) and laryngeal SCCs (69.2%; 95% CI, 64.0-74.0). Conversely, HPV18 was rare in HPV-positive oropharyngeal SCCs (2.8%; 95% CI, 1.3-5.3) compared with other head and neck sites [34.1% (95% CI, 30.4-38.0) of oral SCCs and 17.0% (95% CI, 13.0-21.6) of laryngeal SCCs]. Aside from HPV16 and HPV18, other oncogenic HPVs were rarely detected in HNSCC. Tumor site–specific HPV prevalence was higher among studies from North America compared with Europe and Asia. The high HPV16 prevalence and the lack of HPV18 in oropharyngeal compared with other HNSCCs may point to specific virus-tissue interactions. Small sample size and publication bias complicate the assessment of the prevalence of HPV in head and neck sites beyond the oropharynx.
Contemporary Lung Cancer Trends among U.S. Women
Authors: Jemal Ahmedin , Ward Elizabeth , Thun Michael J.
Published: September 2005

The age-standardized lung cancer incidence rate among women in the United States has decreased for each of the last 3 years for which data are available (1999-2001). We conducted this study to assess the stability and near-term sustainability of this decrease. We examined temporal trends in age-specific lung cancer incidence by calendar year and birth cohort and measured trends in the age-standardized rate in each geographic area within the Surveillance, Epidemiology, and End Results (SEER) Program using joinpoint regression analyses. Age-standardized lung cancer incidence rates have peaked or are decreasing in all geographic areas within SEER, although the decline is statistically significant only in San Francisco-Oakland. Age-specific incidence rates are decreasing in six of the seven 5-year age groups between ages 50 and 84 years in all areas of SEER combined. Rates in these age groups contribute nearly 95% of the total age-standardized incidence rate; consequently, trends in incidence at these ages will determine future trends in the overall age-standardized incidence rate for the next 20 to 25 years. Birth cohort patterns suggest that the decrease in the age-standardized rate will continue for at least 20 years, but will be slowed by aging of women born in the late 1950s and early 1960s. Given calendar year and birth cohort age-specific incidence patterns, the early decline in lung cancer incidence among women is likely to persist through at least 2025. Sustaining the downward trend beyond 2025 will require continued reductions in smoking initiation among children and increases in cessation among addicted smokers.
Circulating Levels of Insulin-like Growth Factors, their Binding Proteins, and Breast Cancer Risk
Authors: Schernhammer Eva S. , Holly Jeff M. , Pollak Michael N. , Hankinson Susan E.
Published: September 2005

Background: Earlier data support the hypothesis that the relation between circulating insulin-like growth factor-I (IGF-I) levels and breast cancer risk differs by menopausal status. The strong association of IGF-I with height in childhood and weak or no association between adult levels and adult height also suggest that IGF levels in young women may better reflect an exposure time period of importance to breast cancer. Few studies have assessed IGF binding protein-1 (IGFBP-1) or free IGF and breast cancer risk.

Materials and Methods: We conducted a large case-control study nested within the prospective Nurses' Health Study. Plasma concentrations of IGF-I, free IGF, IGFBP-3, and IGFBP-1 were measured in blood samples collected in 1989 to 1990. Eight hundred women were identified who had a diagnosis of invasive or in situ breast cancer after blood collection, up to 1998, 27% of whom were premenopausal at blood collection. To those 800 women, one to two controls were age-matched for a total of 1,129 controls. We used logistic regression models to estimate the relative risk (RR) of breast cancer associated with IGF levels.

Findings: Among postmenopausal women, neither IGF-I, IGFBP-3, IGFBP-1, nor free IGF was associated with breast cancer risk [RRs, top versus bottom quintile: IGF-I, 1.0; 95% confidence interval (95% CI), 0.7-1.4; IGFBP-3, 0.8; 95% CI, 0.6-1.1; IGFBP-1, 0.9; 95% CI, 0.6-1.5; and free IGF, 1.0; 95% CI, 0.6-1.4]. Among premenopausal women, IGFBP-3, IGFBP-1, and free IGF similarly were not associated with breast cancer risk (RRs, top versus bottom quintile: IGFBP-3, 1.2; 95% CI, 0.8-2.3; IGFBP-1, 1.5; 95% CI, 0.8-3.0; and free IGF, 1.1; 95% CI, 0.7-2.1). Higher IGF-I plasma levels, however, were associated with a modestly elevated breast cancer risk (RR, 1.6; 95% CI, 1.0-2.6) among the premenopausal women, with a stronger association among premenopausal women ages ≤50 (RR, 2.5; 95% CI, 1.4-4.3); further adjustment for IGFBP-3 did not greatly change these estimates.

Interpretation: Circulating IGF-I levels seem to be modestly associated with breast cancer risk among premenopausal women, but not among postmenopausal women. IGFBP-3, IGFBP-1, and free IGF are not associated with breast cancer risk in either premenopausal or postmenopausal women in this cohort.
Neighborhood Socioeconomic Status and Hodgkin's Lymphoma Incidence in California
Authors: Clarke Christina A. , Glaser Sally L. , Keegan Theresa H.M. , Stroup Antoinette
Published: September 2005

Hodgkin's lymphoma occurrence has long been noted to associate with higher socioeconomic status (SES). However, the Hodgkin's lymphoma-SES association has not been examined recently or across important, possibly etiologically distinct, patient subgroups. In ∼150 million person-years of observation in the multiethnic population of California, we examined the association of Hodgkin's lymphoma incidence with a composite measure of neighborhood-level SES in patient subgroups defined by age, sex, race/ethnicity, and Hodgkin's lymphoma histologic subtype. Using population-based cancer registry data on 3,794 Hodgkin's lymphoma patients diagnosed 1988 to 1992 and 1990 census data, we assigned a previously validated, multidimensional SES index to census block groups of patient residence. We then calculated neighborhood SES-specific incidence rates and estimated rate ratios using Poisson regression. Positive neighborhood SES gradients in Hodgkin's lymphoma incidence were observed only in young adults (ages 15-44 years at diagnosis) with nodular sclerosis Hodgkin's lymphoma and older adult (ages ≥45 years) White and Hispanic males with mixed cellularity Hodgkin's lymphoma. For young adults, associations were marked in Hispanic and Asian women, weaker in Hispanic and White men and White women, and subtle to nonexistent in Blacks and Asian men. Neighborhood SES gradients in Hodgkin's lymphoma incidence varied by age, sex, race/ethnicity, and histologic subtype, underscoring etiologic complexity in Hodgkin's lymphoma. Racial/ethnic gradients were not entirely explained by neighborhood SES. In California, etiologically relevant exposures for young adult Hodgkin's lymphoma, the most common form, could associate more with race/ethnicity or foreign birthplace than neighborhood SES and may be modified by reproductive or other sex-specific factors.
No Evidence for BRAF as a Melanoma/Nevus Susceptibility Gene
Authors: Jackson Sharon , Harland Mark , Turner Faye , Taylor Claire , Chambers Philip A. , Randerson-Moor Juliette , Swerdlow Anthony J. , dos Santos Silva Isabel , Beswick Samantha , Bishop D. Timothy , Newton Bishop Julia A.
Published: September 2005

Somatic mutations of BRAF have been identified in both melanoma tumors and benign nevi. Germ line mutations in BRAF have not been identified as causal in families predisposed to melanoma. However, a recent study suggested that a BRAF haplotype was associated with risk of sporadic melanoma in men. Polymorphisms or other variants in the BRAF gene may therefore act as candidate low-penetrance genes for nevus/melanoma susceptibility. We hypothesized that promoter variants would be the most likely candidates for determinants of risk. Using denaturing high-pressure liquid chromatography and sequencing, we screened peripheral blood DNA from 184 familial melanoma cases for BRAF promoter variants. We identified a promoter insertion/deletion in linkage disequilibrium with the previously described BRAF polymorphism in intron 11 (rs1639679) reported to be associated with melanoma susceptibility in males. We therefore investigated the contribution of this BRAF polymorphism to melanoma susceptibility in 581 consecutively recruited incident cases, 258 incident cases in a study of late relapse, 673 female general practitioner controls, and the 184 familial cases. We found no statistically significant difference in either genotype or allele frequencies between cases and controls overall or between male and female cases for the BRAF polymorphism in the two incident case series. Our results therefore suggest that the BRAF polymorphism is not significantly associated with melanoma and the promoter insertion/deletion linked with the polymorphism is not a causal variant. In addition, we found that there was no association between the BRAF genotype and mean total number of banal or atypical nevi in either the cases or controls.
A Prospective Study of Dietary Folate Intake and Risk of Colorectal Cancer: Modification by Caffeine Intake and Cigarette Smoking
Authors: Larsson Susanna C. , Giovannucci Edward , Wolk Alicja
Published: September 2005

Epidemiologic evidence indicates an inverse association of folate intake with risk of colorectal cancer, but whether this association is modified by intake of caffeine (in coffee and tea) or cigarette smoking—factors that possibly interfere with folate—has not been studied. Thus, we examined whether the association between dietary folate intake and incidence of colorectal cancer is modified by caffeine intake and smoking. Cox proportional hazards modeling was used to estimate rate ratios relating dietary folate intake to colorectal cancer incidence among 61,433 women ages 40 to 75 years at recruitment into the Swedish Mammography Cohort in 1987 to 1990. From March 1987 through June 2004, a total of 805 incident cases of colorectal cancer were diagnosed. After controlling for age and other potential confounders, we observed an inverse association between dietary folate intake and risk of colon cancer (rate ratio for the highest versus the lowest quintile, 0.61; 95% confidence interval, 0.41-0.91; Ptrend = 0.02), but not of rectal cancer (rate ratio, 0.93; 95% confidence interval, 0.55-1.56; Ptrend = 0.97). The inverse association between dietary folate intake and colon cancer risk was most pronounced among smokers (Pinteraction = 0.03). We found no apparent modification of risk by caffeine intake. Findings from this population-based cohort study support an inverse association between dietary folate intake and risk of colon cancer and suggest that smokers might benefit most from a high dietary folate intake.
Chlamydia pneumoniae and Lung Cancer: Epidemiologic Evidence
Authors: Littman Alyson J. , Jackson Lisa A. , Vaughan Thomas L.
Published: September 2005

Chlamydia pneumoniae is a common cause of acute respiratory infection and has been hypothesized to cause several chronic diseases, including lung cancer. The purpose of this article is to identify, describe, and critically examine the published studies on the association between C. pneumoniae infection and risk of lung cancer. In the six studies identified, previous C. pneumoniae infection was defined on the basis of serologic criteria, which varied between studies. All studies reported elevated relative risk estimates for the association of serologic evidence of infection and risk of lung cancer. The three studies in which past infection was defined based on testing of prediagnostic blood specimens tended to have weaker results (odds ratio range, 1.2-2.1) than those based on postdiagnostic blood specimens (odds ratio range, 1.4-9.9). Selection bias, measurement error, and inadequate control for confounding are concerns in some of these studies. Nevertheless, results were relatively consistent, supporting a causal association. Inflammation caused by chronic infection with C. pneumoniae may be involved in the carcinogenic process but this relationship will be difficult to further define through serologic data. To better understand the nature of this association, both experimental study designs, such as those based on animal models or randomized controlled antibiotic treatment trials in humans, and observational study designs (e.g., studies that involve detection of C. pneumoniae in pulmonary specimens obtained before cancer onset) could be explored and may shed additional light on this important association.
Gene-Smoking Interaction Associations for the ERCC1 Polymorphisms in the Risk of Lung Cancer
Authors: Zhou Wei , Liu Geoffrey , Park Sohee , Wang Zhaoxi , Wain John C. , Lynch Thomas J. , Su Li , Christiani David C.
Published: September 2005

Cigarette smoking may induce DNA damage. Lower DNA repair capacities have been associated with higher risk of lung cancer. Excision repair cross-complementing group 1 (ERCC1) is the lead enzyme in the nucleotide excision repair process, and low expression of ERCC1 mRNA levels has been associated with higher risk of cancers. We examined the association between two polymorphisms of ERCC1, 8092C > A (rs3212986) and 19007T > C (codon 118, rs11615), which are associated with altered ERCC1 mRNA stability and mRNA levels, in 1,752 Caucasian lung cancer patients and 1,358 controls. The results were analyzed using logistic regression models, adjusting for relevant covariates. The two polymorphisms were in Hardy-Weinberg disequilibrium and in linkage disequilibrium. There was no overall association between ERCC1 polymorphisms and lung cancer risk, with the adjusted odds ratios (AOR) of 1.26 [95% confidence interval (95% CI), 0.81-1.96] for the 8092C > A polymorphism (A/A versus C/C) and 0.93 (95% CI, 0.67-1.30) for the 19007T > C polymorphism (C/C versus T/T). Stratified analyses revealed that the AORs for the 8092C > A polymorphism (A/A versus C/C) decreased significantly as pack-years increased, with the AOR of 2.11 (95% CI, 1.03-4.31) in never smokers and 0.50 (95% CI, 0.25-1.01) in heavy smokers (≥56 pack-years), respectively. Consistent results were found when gene-smoking interaction was incorporated by joint effects and interactions models that considered both discrete and continuous variables for cumulative smoking exposure. The same direction for the gene-smoking interaction was found for the 19007T > C polymorphism, although the interaction was not statistically significant. In conclusion, ERCC1 8092C > A polymorphism may modify the associations between cumulative cigarette smoking and lung cancer risk.
Levels of Physical Activity for Colon Cancer Prevention Compared with Generic Public Health Recommendations: Population Prevalence and Sociodemographic Correlates
Authors: Cerin Ester , Leslie Eva , Bauman Adrian , Owen Neville
Published: September 2005

Background: The proportion of Australian adults achieving physical activity levels believed to be sufficient for colon cancer prevention was estimated, and sociodemographic correlates (age, gender, educational attainment, occupation, marital status, and children in household) of meeting these levels of activity were analyzed.

Methods: Data from the 2000 National Physical Activity Survey were used to estimate the prevalence of participation in physical activity in relation to three criteria: generic public health recommendations, weekly amount of at least moderate-intensity physical activity currently believed to reduce risk of colon cancer, and weekly amount of vigorous-intensity physical activity believed to reduce risk of colon cancer.

Results: Overall, 46% of adults met the generic public health criterion, 26% met the colon cancer criterion based on participation in at least moderate-intensity physical activity, and 10% met the colon cancer criterion based on vigorous-intensity physical activity. Women were less likely than men to meet the colon cancer criteria. Younger and more educated persons were more likely to meet all three criteria. The most pronounced differences between gender, age, and educational attainment groups were found for meeting the amount of vigorous-intensity physical activity believed to reduce risk of colon cancer.

Conclusions: The population prevalence for meeting proposed physical activity criteria for colon cancer prevention is low and much lower than that related to the more generic public health recommendations. If further epidemiologic studies confirm that high volumes and intensities of activity are required, the public health challenges for colon cancer will be significant.
A Noninvasive Objective Measure of Sunscreen Use and Reapplication
Authors: O'Riordan David L. , Lunde Kevin B. , Urschitz Johann , Glanz Karen
Published: September 2005

Objectives: To study whether a noninvasive swabbing technique can detect sunscreen use for up to 6 hours, and whether the technique can detect reapplication of sunscreen.

Methods: Thirty volunteer office workers were randomly assigned to have one of a variety of sunscreens applied using recommended application techniques, and half were randomly assigned to have sunscreen reapplied after 3 hours. Alcohol-based swabs were used to obtain a sample from participants' arm at 20 minutes, and hourly from 1 to 6 hours post-application. Absorption readings were analyzed using an UV-visible spectrophotometer.

Results: The swabbing technique was consistently able to distinguish the sunscreen from control swabs for up to 6 hours. The absorption readings between 20 minutes and 6 hours were significantly higher than control swabs. There were no differences between the group that had sunscreen reapplied and the group that did not.

Conclusion: The sunscreen swabbing technique is an effective noninvasive method for detecting a variety of sunscreen products in adults over a 6-hour period. No differences in absorption readings were found with sunscreen reapplication. This procedure will be a useful adjunct to other objective measures of sun protection and UV radiation exposure, resulting in a more accurate picture of the sun protection habits of individuals.
TP53 Mutation Spectrum in Lung Cancer Is Not Different in Women and Men
Authors: Marrogi Aizen J. , Mechanic Leah E. , Welsh Judith A. , Bowman Elise D. , Khan Mohammed A. , Enewold Lindsey , Shields Peter G. , Harris Curtis C.
Published: September 2005

Whether women are more susceptible to lung cancer than men has been controversial. Several case-control studies suggested that women have greater risk of lung cancer compared with men at similar levels of cigarette smoking, whereas some large cohort studies failed to observe this association. Other studies indicated that lung cancer may have biological characteristics and mechanisms of carcinogenesis that are gender specific. Therefore, we hypothesized that women are more susceptible to the carcinogenic effects of tobacco smoke exposure, as evidenced by a higher frequency of G:C-to-T:A somatic mutations in tumors from women in comparison with men at similar levels of tobacco smoke exposure. To investigate our hypothesis, we examined the TP53 mutational spectrum in a case-only (102 women and 201 men) series study where complete smoking information was available. A similar frequency and type of somatic TP53 mutations were observed in women and men. In conclusion, our study indicates that the TP53 mutation spectrum is similar in women and men. Our results are consistent with a recent large cohort study and summary of previous cohort studies, suggesting that women likely have equivalent susceptibility to lung cancer as men.