bluuebunny/crossref_metadata_2025 huggingface dataset:
Longitudinal Study of Urinary Phenanthrene Metabolite Ratios: Effect of Smoking on the Diol Epoxide Pathway
Authors: Hecht Stephen S. , Chen Menglan , Yoder Andrea , Jensen Joni , Hatsukami Dorothy , Le Chap , Carmella Steven G.
Published: March 2006

We have proposed that urinary phenanthrene metabolites could be used in a carcinogen metabolite phenotyping approach to identify individuals who may be susceptible to cancer induction by polycyclic aromatic hydrocarbons (PAH). In support of this proposal, we have developed methods for quantitation of r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (PheT) and phenanthrols (HOPhe) in human urine. PheT is the end product of the diol epoxide metabolic activation pathway of PAH, whereas HOPhe are considered as detoxification products. In this study, we investigated the longitudinal consistency of these metabolites over time in smokers and nonsmokers and compared their levels. Twelve smokers and 10 nonsmokers provided urine samples daily for 7 days, then weekly for 6 weeks. Levels of PheT, HOPhe, and PheT/HOPhe ratios were relatively constant in most individuals, with mean coefficients of variation ranging from 29.3% to 45.7%. There were no significant changes over time in levels of the metabolites or in ratios. These results indicate that a single urine sample should be sufficient when comparing phenanthrene metabolites in different groups. PheT/HOPhe ratios were significantly higher in smokers than in nonsmokers, showing that smoking induces the diol epoxide metabolic activation pathway of phenanthrene. This finding is consistent with previous studies indicating that inducibility of PAH metabolism contributes to cancer risk in smokers. (Cancer Epidemiol Biomarkers Prev 2005;14(12):2969–74)
No Association Between EGF Gene Polymorphism and Gastric Cancer
Authors: Goto Yasuyuki , Ando Takafumi , Goto Hidemi , Hamajima Nobuyuki
Published: March 2006

The etiology of gastric cancer is not well-understood. Epidermal growth factor (EGF) transduces growth signals to mitogen-activated protein kinase via RAS and BRAF, and EGF/EGF receptor interaction is important for tumor growth and progression. Previous studies have reported that the EGF +61 (A/G) single nucleotide polymorphism in the 5′-untranslated region of the EGF gene is functional, and is associated with gastric cancer and various malignancy. Individuals with the EGF A/A genotype produce less EGF than individuals with G/G or G/A. We investigated a single nucleotide polymorphism at exon 1 of EGF, named rs4444903 in NCI dbSNP, in 454 Japanese subjects undergoing a health checkup and 202 patients with gastric cancer. Genotype was determined by PCR with confronting two-pair primers. Results showed that EGF polymorphism was not associated with gastric cancer but that the EGF A/A genotype showed a protective effect (odds ratios, 0.58; 95% confidence interval, 0.29-1.17 relative to G/G). Furthermore, when we divided cases into two groups, a differentiated type and an undifferentiated type, the A/A and G/A combined was found to be lower frequency in the latter type than in the former type without significance (OR, 0.81; 95% confidence interval, 0.44-1.49 relative to G/G). As is the case with any malignancy, other factors are involved, including environmental and host factors. The present results show that although EGF is necessary for cancer, it is not sufficient. We also found ethnic heterogeneity in the functional EGF polymorphism. Because the relationship between EGF polymorphism and malignancy remains inconsistent, confirmation of the role of EGF polymorphism in gastric cancer requires a much larger study.
Fertility Among Brothers of Patients with Testicular Cancer
Authors: Richiardi Lorenzo , Akre Olof
Published: March 2006

Objective: Patients with testicular cancer have decreased fertility prior to the diagnosis of cancer, although it is not clear whether the subfertility is the result of an emerging tumor, or whether subfertility and testicular cancer share causes. To test if they share causes, we assessed fertility among brothers of patients with testicular cancer.

Methods: We compared 5,613 siblings (2,878 brothers) of patients with germ-cell testicular cancer, diagnosed in Sweden from 1960 to 2002, with 6,151 population controls (3,202 men). Using the Swedish Multi-Generation Register, we obtained information on the number of children born (until December 2003) from cases (n = 9,480) and controls (n = 10,739). Fertility was measured using two indicators, (a) offspring twinning rates, as dizygotic twinning is reduced by male subfertility, and (b) number of children. We used unconditional logistic regression, and analyzed brothers and sisters separately. Analyses on the number of children were restricted to subjects (39%) born prior to 1954, for whom information on reproductive life until age 50 was available.

Results: Brothers, but not sisters, of patients with testicular cancer were less likely to have unlike-sex twins than controls (for unlike-sex twins, the odds ratio for the father being a sibling of testicular cancer patient was 0.53; 95% confidence interval, 0.26-1.09). The likelihood of being a brother of a patient with testicular cancer decreased monotonically with increasing number of children (P = 0.05), whereas no association was observed for the sisters.

Conclusion: The decreased fertility found among brothers of patients with testicular cancer argues in favor of shared causes between cancer-associated subfertility and testicular cancer. Genetic links and shared environment could explain the association.
Nipple Fluid Basic Fibroblast Growth Factor in Patients with Breast Cancer
Authors: Sartippour Maryam R. , Zhang Liping , Lu Ming , Wang He-Jing , Brooks Mai N.
Published: March 2006

Purpose: It has been shown that early detection of breast cancer could save lives. Recently, there has been increasing interest in nipple fluid as a potential supplemental avenue for breast cancer diagnosis.

Experimental Design: In this study, we determined the levels of an angiogenic factor basic fibroblast growth factor (bFGF) in the nipple fluid of healthy subjects as well as patients with benign breast conditions, those at high risk for breast cancer, and patients with active breast cancer. ELISAs were used to measure bFGF.

Results: Nipple fluid bFGF levels were as follows (mean ± SE): 158 ± 17 pg/mL from benign breasts, 561 ± 277 pg/mL from high-risk breasts, and 1,343 ± 441 pg/mL from cancerous breasts. One-way ANOVA showed that the bFGF levels from cancerous breasts were significantly higher than those from benign and high-risk breasts (P = 0.0001 and P = 0.0193, respectively). After logarithmic transformation was applied to the data, high-risk breast bFGF levels were higher than those from benign breasts (P = 0.0028). With a cutoff level of 250 pg/mL, the sensitivity was 79.2%, specificity was 82.5%, and correct diagnosis was 66.4%. The area under the receiver operating characteristic curve was 0.86.

Conclusions: We conclude that nipple fluid bFGF levels are progressively elevated in high-risk and cancerous breasts compared with benign breasts. The sensitivity and specificity of this test are promising compared with current breast cancer screening methods, and this test deserves further studies with larger clinical trials. Potential areas of usefulness include the detection of breast cancer risk or breast cancer, as well as the monitoring and/or prediction of the antiangiogenic effect of preventive therapies. (Cancer Epidemiol Biomarkers Prev 2005;14(12):2995–8)
Regular Analgesic Use and Risk of Endometrial Cancer
Authors: Moysich Kirsten B. , Baker Julie A. , Rodabaugh Kerry J. , Villella Jeannine A.
Published: March 2006

Background: Analgesic use has been implicated in the chemoprevention of a number of solid tumors, but thus far, no previous research has focused on the role of aspirin in endometrial cancer etiology.

Methods: We conducted a hospital-based case-control study of 427 women with primary, incident endometrial cancer, and 427 age- and residence-matched controls without benign or malignant neoplasms. All participants received medical services at Roswell Park Cancer Institute in Buffalo, NY, and completed a comprehensive epidemiologic questionnaire. Women who reported analgesic use at least once a week for at least 6 months were classified as regular users and served as the reference group throughout the analyses. We used unconditional logistic regression analyses to compute crude and adjusted odds ratios (OR) with corresponding 95% confidence intervals (CI).

Results: Compared with nonusers, regular aspirin users were not at reduced risk of endometrial cancer (adjusted OR, 0.91; 95% CI, 0.66-1.26), nor were women with the highest frequency, duration, or cumulative lifetime aspirin use. When the sample was divided by body mass index status, regular aspirin use was not associated with risk among women classified as normal weight or overweight, but a significant risk reduction was seen for obese women (adjusted OR, 0.50; 95% CI, 0.27-0.92). Significant decreases in risk were also observed for obese women with the greatest frequency, duration, and cumulative aspirin use. No significant associations in the overall sample or among obese women were noted for acetaminophen use.

Conclusion: We observed no evidence of an overall chemoprotective effect of aspirin on endometrial cancer risk, but the significant risk reductions among obese women warrant further investigation. (Cancer Epidemiol Biomarkers Prev 2005;14(12):2923–8)
Prevalence and Clustering Patterns of Human Papillomavirus Genotypes in Multiple Infections
Authors: Chaturvedi Anil K. , Myers Leann , Hammons Ansley F. , Clark Rebecca A. , Dunlap Kathleen , Kissinger Patricia J. , Hagensee Michael E.
Published: March 2006

Prevalence of multiple human papillomavirus (HPV) infections, involvement of specific HPV phylogenetic clades in multiple infections, and clustering patterns of multiple infections at the clade level were assessed in 854 HIV (−) and 275 HIV (+) women cross-sectionally. Reverse line blot assay was used to detect 27 HPV genotypes. Involvement of specific clades in coinfections and clustering patterns were assessed using HPV clade/genotype as the unit of analyses. Expected frequencies assuming independence for all possible clade combinations in two-genotype infections were derived using a multinomial expansion and comparisons of observed and expected frequencies were done using a composite goodness-of-fit test. In all, 100 two-genotype infections were detected; 61 in HIV (−) and 39 in HIV (+) women. Clade A9 (HPV types 16, 31, 33, 35, 52, and 58) was significantly less likely to be involved in multiple infections compared with all other clades (55.2% versus 64.6%; adjusted odds ratios, 0.68; 95% confidence interval, 0.48-0.95). Observed patterns for all possible clade combinations (among HPV clades A3, A5, A6, A7, A9, and A10) in two-genotype infections did not significantly differ from those expected in the entire sample, across HIV, Pap smear, and age strata (all goodness-of-fit exact P > 0.20). These results indicate that clade A9 is less likely to be involved in multiple infections and that HPV genotypes predominantly establish multiple infections at random, with little positive/negative clustering for either phylogenetically related or unrelated types. The current method of analysis affords the opportunity to test clustering of a large number of HPV genotype/clade combinations at nominal alpha levels.
The Predicted Impact of Coding Single Nucleotide Polymorphisms Database
Authors: Rudd Matthew F. , Williams Richard D. , Webb Emily L. , Schmidt Steffen , Sellick Gabrielle S. , Houlston Richard S.
Published: March 2006

Nonsynonymous single nucleotide polymorphisms (nsSNP) have the potential to affect the structure or function of expressed proteins and are, therefore, likely to represent modifiers of inherited susceptibility. We have classified and catalogued the predicted functionality of nsSNPs in genes relevant to the biology of cancer to facilitate sequence-based association studies. Candidate genes were identified using targeted search terms and pathways to interrogate the Gene Ontology Consortium database, Kyoto Encyclopedia of Genes and Genomes database, Iobion's Interaction Explorer PathwayAssist Program, National Center for Biotechnology Information Entrez Gene database, and CancerGene database. A total of 9,537 validated nsSNPs located within annotated genes were retrieved from National Center for Biotechnology Information dbSNP Build 123. Filtering this list and linking it to 7,080 candidate genes yielded 3,666 validated nsSNPs with minor allele frequencies ≥0.01 in Caucasian populations. The functional effect of nsSNPs in genes with a single mRNA transcript was predicted using three computational tools—Grantham matrix, Polymorphism Phenotyping, and Sorting Intolerant from Tolerant algorithms. The resultant pool of 3,009 fully annotated nsSNPs is accessible from the Predicted Impact of Coding SNPs database at http://www.icr.ac.uk/cancgen/molgen/MolPopGen_PICS_database.htm. Predicted Impact of Coding SNPs is an ongoing project that will continue to curate and release data on the putative functionality of coding SNPs.
Estrogen and Progesterone Levels in Nipple Aspirate Fluid of Healthy Premenopausal Women: Relationship to Steroid Precursors and Response Proteins
Authors: Gann Peter H. , Geiger Angela S. , Helenowski Irene B. , Vonesh Edward F. , Chatterton Robert T.
Published: March 2006

Background: Concentrations of estrogen and progesterone within the breast could provide a better reflection of breast cancer risk than levels in the circulation. We developed highly sensitive immunoassays for multiple steroid hormones and proteins in the nipple aspirate fluid (NAF), which can be obtained noninvasively with a simple suction device. Previous studies showed that NAF hormone levels are strongly correlated between breasts and within a single breast over time and are predictably related to hormone replacement therapy or use of oral contraceptives. This study evaluates the relationship of NAF estrogen and progesterone levels to those in serum and saliva, the relationship of NAF estradiol to androgenic and estrogenic precursors in NAF, and the relationship of NAF hormone levels to those of response proteins such as cathepsin D and epidermal growth factor (EGF).

Methods: Normal premenopausal women collected saliva daily and donated blood and NAF in the midluteal phases of menstrual cycles at intervals of 0, 4, 12, and 15 months. Analytes were measured by immunoassays after solvent fractionation. Log-transformed values were fit to repeated measures analysis of covariance models to ascertain associations between analytes.

Results: Small nonsignificant associations were found between NAF and serum or salivary estradiol. However, progesterone in NAF was significantly associated with progesterone in serum and saliva (R = 0.18 and 0.32, respectively). Within NAF, the estradiol precursors estrone sulfate, androstenedione, and dehydroepiandrosterone were significantly associated with estradiol concentration (P < 0.06), and a multiprecursor model explained the majority of variance in NAF estradiol (model R2 = 0.83). Cathepsin D and EGF in NAF could not be predicted from serum or salivary steroid measurements; however, both could be predicted from estradiol and its precursors in NAF (model R2 = 0.70 and 0.93, respectively).

Conclusions: By showing consistent associations between estradiol and its precursors and response proteins, these data provide support for the biological validity of NAF hormone measurements and for the importance of steroid interconversion by aromatase and sulfatase within the breast. The low correlation between estrogen levels in NAF and those in serum or saliva suggests that the degree of association between estrogen or its androgen precursor levels and risk of breast cancer observed in epidemiologic studies using serum estimates might be highly attenuated. (Cancer Epidemiol Biomarkers Prev 2006;15(1):39–44)
High Serum Selenium and Reduced Risk of Advanced Colorectal Adenoma in a Colorectal Cancer Early Detection Program
Authors: Peters Ulrike , Chatterjee Nilanjan , Church Timothy R. , Mayo Charlotte , Sturup Stefan , Foster Charles B. , Schatzkin Arthur , Hayes Richard B.
Published: March 2006

Background: Epidemiologic and animal studies suggest that selenium may reduce risk of colorectal cancer. However, the epidemiologic data is mainly from relatively small investigations, limiting their interpretation. Although substantial evidence suggests that smoking is a strong effect modifier for other antioxidative nutrients, little is known about smoking-selenium interactions in colorectal tumors.

Methods: We studied the association of serum selenium and advanced colorectal adenoma, a cancer precursor, in 758 cases and 767 sex- and race-matched controls, randomly selected from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Cases had at least one verified advanced adenoma (≥1 cm or villous elements, or high-grade dysplasia) of the distal colon, and controls had a negative sigmoidoscopy.

Results: The multivariable odds ratio (OR) comparing participants in the highest quintile of serum selenium with those in the lowest quintile was 0.76 [95% confidence interval (95% CI), 0.53-1.10; Ptrend = 0.01]. The inverse association between serum selenium and advanced colorectal adenoma was significant among recent smokers (OR, 0.53; 95% CI, 0.27-1.01 for highest versus lowest tertile; Ptrend = 0.008). Serum selenium was unrelated to adenoma risk in nonsmokers and former smokers who quit smoking ≥10 years ago.

Conclusion: Selenium may reduce the risk of developing advanced colorectal adenoma, particularly among the high-risk group of recent smokers. (Cancer Epidemiol Biomarkers Prev 2006;15(2):315–20)
Sun-Protective Behavior among Individuals with a Family History of Melanoma
Authors: Azzarello Lora M. , Dessureault Sophie , Jacobsen Paul B.
Published: March 2006

Routine sun protection is recommended to prevent skin cancer. Skin cancer prevention may be particularly important for individuals at greater risk, such as those with a family history of melanoma. Our aims were to examine the prevalence of sun-protective behavior (SPB) in unaffected first-degree relatives (FDR) of individuals diagnosed with melanoma and to examine the relationship between protection motivation theory (PMT) variables (i.e., perceived risk, perceived severity, self-efficacy, response efficacy) and SPB. FDRs (n = 100), who were nominated by melanoma patients, completed a standardized, self-report questionnaire measuring demographic characteristics, melanoma risk factors, PMT variables, and SPB. The results indicated that less than one-third of FDRs used sunscreen routinely when in the sun and fewer stayed in the shade or used protective clothing on a frequent basis. FDRs with a college education and with more melanoma risk factors reported higher levels of SPB. Of the four PMT variables, greater perceived risk and greater self-efficacy were significantly correlated with higher levels of SPB. Furthermore, results of multiple regression analyses suggest that perceived risk mediated the relationship between education and SPB and between melanoma risk factors and SPB. These findings suggest that interventions to increase the frequency of SPB in at-risk individuals should highlight risk information as well as methods to improve individuals' confidence in their abilities to engage in SPB. (Cancer Epidemiol Biomarkers Prev 2006;15(1):142–5)
Association of Energy Intake and Energy Balance with Postmenopausal Breast Cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial
Authors: Chang Shih-Chen , Ziegler Regina G. , Dunn Barbara , Stolzenberg-Solomon Rachael , Lacey James V. , Huang Wen-Yi , Schatzkin Arthur , Reding Douglas , Hoover Robert N. , Hartge Patricia , Leitzmann Michael F.
Published: March 2006

Energy restriction remains one of the most effective ways known to prevent breast cancer in animal models. However, energy intake has not been consistently associated with risk of breast cancer in humans. In a prospective study, we assessed whether energy intake, body size, and physical activity each independently influence breast cancer risk in postmenopausal women and estimated the joint effect of combinations of these individual factors. As part of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, 38,660 women, ages 55 to 74 years and recruited from 10 centers in the United States during 1993 to 2001, were randomized to the screening arm of the trial. At baseline, the women completed a self-administered questionnaire, including a food frequency questionnaire. During follow-up from 1993 to 2003, 764 incident breast cancer cases were ascertained. Women in the highest quartile of energy intake (≥2,084 kcal/d) compared with those in the lowest quartile (<1,316 kcal/d) had a significantly increased risk for breast cancer [multivariate relative risk (RR), 1.25; 95% confidence interval (95% CI), 1.02-1.53; Ptrend continuous = 0.03]. Current body mass index (BMI) was also positively and significantly associated with risk (multivariate RR comparing >30 kg/m2 with <22.5 kg/m2, 1.35; 95% CI, 1.06-1.70; Ptrend = 0.01). Women with ≥4 hours/wk of vigorous recreational physical activity had a significantly reduced risk of breast cancer compared with those who reported no recreational physical activity (multivariate RR, 0.78; 95% CI, 0.60-0.99; Ptrend = 0.15). None of these associations with individual energy balance measures was substantially confounded by the other two measures. When we estimated the joint effect of all three variables, women with the most unfavorable energy balance (the highest energy intake, highest BMI, and least physical activity) had twice the risk (RR, 2.10; 95% CI, 1.27-3.45) of women with the most favorable energy balance (the lowest energy intake, lowest BMI, and most physical activity). Although our estimates of absolute energy intake, based on a food frequency questionnaire, are imperfect, these results suggest that energy intake, in addition to BMI and physical activity may be independently associated with breast cancer risk. In addition, these three aspects of energy balance may act jointly in determining breast cancer risk. (Cancer Epidemiol Prev 2006;15(2):334–41)
Inflammation and Endometrial Cancer: A Hypothesis
Authors: Modugno Francesmary , Ness Roberta B. , Chen Chu , Weiss Noel S.
Published: March 2006

Endometrial cancer is the most common gynecologic malignancy in the United States. Substantial epidemiologic data implicate an imbalance of estrogens and progestogens in the etiology of this disease. We propose that inflammation also plays a role in endometrial cancer development. Emerging laboratory data suggest that elevated levels of prostaglandin E2 may underlie the transformation of normal endometrium to neoplastic tissue and that in vitro nonsteroidal anti-inflammatory drugs may inhibit endometrial cancer cell growth. In this review, we suggest that the risk factors for endometrial cancer—unopposed estrogens, anovulation, polycystic ovary syndrome, excessive menstruation, early menarche, and late menopause—may be viewed as factors increasing the exposure of the endometrium to inflammation, whereas pregnancy and smoking, two likely protective factors, have the opposite effect. Chronic inflammation can induce rapid cell division, increasing the possibility for replication error, ineffective DNA repair, and subsequent mutations. A proinflammatory milieu can also directly increase estrogen production. Hence, inflammation may work in conjunction with or in addition to estrogen exposure in the development of endometrial cancer. (Cancer Epidemiol Biomarkers Prev 2005;14(12):2840–7)
Sun Protection and the Development of Melanocytic Nevi in Children
Authors: English Dallas R. , Milne Elizabeth , Simpson Julie A.
Published: March 2006

Childhood sun exposure causes nevi (and melanoma), but there is little evidence regarding the effectiveness of sun protection strategies on the number of nevi. We previously found that boys but not girls receiving a school-based sun protection program had fewer nevi on their backs than controls. Here, we investigated whether specific program components (encouraging children to stay indoors in the middle of the day during summer, to wear clothing while outdoors, and to use sunscreen) were associated with fewer nevi. An observational analysis was done on data from a sun protection trial in 1,623 children in Perth, Australia. The outcome was number of nevi on the back 6 years after baseline, when the children were 12 years old. Information on sun protection was obtained by questionnaires 4 and 6 years after baseline. The data were analyzed by mixed-effects linear regression. The time spent outdoors between 11 a.m. and 2 p.m. and the proportion of total time outdoors that was between these hours were positively associated with number of nevi. Ratios of mean counts for doubling the respective measures were 1.09 [95% confidence interval (95% CI), 1.05-1.12] and 1.10 (95% CI, 1.05-1.14). Children whose backs were covered <70% of the time while outdoors had 1.53 (95% CI, 1.34-1.75) times more nevi than children whose backs were always covered. Using sunscreen on the back when it was uncovered was not associated with number of nevi (P = 0.59). Children who stayed indoors in the middle of the day and wore clothing while outdoors had fewer nevi. (Cancer Epidemiol Biomarkers Prev 2005;14(12):2873–6)
Early Life Factors and Incidence of Proliferative Benign Breast Disease
Authors: Baer Heather J. , Schnitt Stuart J. , Connolly James L. , Byrne Celia , Willett Walter C. , Rosner Bernard , Colditz Graham A.
Published: March 2006

Proliferative benign breast disease is a marker of increased breast cancer risk, yet little is known about its etiology. Most studies of benign breast disease have focused only on risk factors in adulthood, despite growing evidence that factors in early life influence breast cancer risk. We explored the relations of several early life factors with incidence of proliferative benign breast disease among 71,896 premenopausal women in the Nurses' Health Study II who recalled their body fatness at young ages, physical activity in adolescence, birthweight, and history of being breastfed. Between 1991 and 1997, 901 of these women were identified as having proliferative benign breast disease from a centralized pathology review. Relative risks (RR) and 95% confidence intervals (95% CI) were estimated from Cox proportional hazards models. Greater childhood body fatness (ages 5-10) was associated with decreased risk of proliferative benign breast disease; the multivariate RR (95% CI) for the most overweight compared with the most lean was 0.61 (0.44-0.86; Ptrend < 0.0001) and remained significant after adjustment for current body mass index. Body mass index at age 18 was also inversely associated with incidence of proliferative benign breast disease, with a multivariate RR (95% CI) of 0.67 (0.52-0.88) for those who were ≥25 kg/m2 compared with those who were <19 kg/m2 (Ptrend = 0.001). There were no clear associations for physical activity in adolescence, birthweight, or being breastfed. These results indicate that premenopausal women who were heavier at young ages have lower incidence of proliferative benign breast disease, consistent with previous findings for breast cancer. (Cancer Epidemiol Biomarkers Prev 2005;14(12):2889–97)
Unlimited Access to Care: Effect on Racial Disparity and Prognostic Factors in Lung Cancer
Authors: Mulligan Charles R. , Meram Amir D. , Proctor Courtney D. , Wu Hongyu , Zhu Kangmin , Marrogi Aizen J.
Published: March 2006

Study Objective: Evaluate the prognostic factors influencing lung cancer survival under a universal health care system and determine if access to care eliminates clinical outcome disparity.

Design: Retrospective case series review.

Background: Lung cancer survival is worse in men and in African Americans, thought to be related to poor general health in men and limited access to heath care in African Americans. The Military Health Care System, with unlimited access to care, provides an excellent setting for evaluating gender and racial disparities in lung cancer survival.

Methods: Lung cancers diagnosed at Walter Reed Army Medical Center, from 1990 to 2000, were evaluated by chart review for age, gender, race, smoking history, cancer history, histology, stage, and completeness of resection.

Results: Seven hundred thirteen Caucasians and 173 African Americans, 2:1 male predominance, had a 22% 5-year survival. Cox model analysis showed that male gender [hazard ratio (HR, 1.31) 95% confidence interval (95% CI), 1.02-1.68], advanced-stage disease (stage III: HR, 2.58; 95% CI, 1.57-4.26/stage IV: HR, 4.20; 95% CI, 2.51-7.41), and incomplete resection (HR, 4.06; 95% CI, 2.75-5.99) were predictors of poor outcome; whereas bronchoalveolar carcinoma features (HR, 0.35; 95% CI, 0.23-0.52) and smoking cessation >7 years (HR, 0.70; 95% CI, 0.49-0.99) were predictors of favorable outcome. No ethnic differences in survival were observed.

Conclusions: No racial disparities in survival when access to medical care is universal. Male gender, incomplete resection, and advanced stage are significant predictors of poor outcome in lung cancer. (Cancer Epidemiol Biomarkers Prev 2006;15(1):25–31)
Diet, Cancer, and the Lipidome
Authors: Bougnoux Philippe , Giraudeau Bruno , Couet Charles
Published: March 2006

The potential for dietary fat to interfere with the development of breast cancer by delaying its occurrence makes the identification of defined molecules a mandatory step in cancer prevention. In order to circumvent the limitations and/or bias of dietary exposure assessment tools, biomarkers of past lipid intake such as the fatty acid composition of white adipose tissue have been used. When considered separately, candidate fatty acids identified as favorable on the basis of their association with breast cancer risk have usually led to inconsistent results in animal intervention studies. This inconsistency indicates that any approach based on a single fatty acid should be abandoned for an integrated view over the complex lipid interactions which finally determines the lipidome, the lipid profile that is found in individuals. This article presents a reappraisal of the role of the lipid profile through a comprehensive reanalysis of adipose tissue fatty acid composition obtained in patients with benign or malignant breast tumors as well as in experimental animals during dietary interventions. Rather than a single fatty acid, a composite indicator combining elevated monounsaturates and low ω6/ω3 fatty acid ratio was associated with breast cancer protection. This lipidome may become the template for identifying breast cancer risk related to diet, and for designing proper dietary modifications to delay the occurrence of breast cancer, although the universality of the findings cannot be assessed from a single study. (Cancer Epidemiol Biomarkers Prev 2006;15(3):416–21)
Catechol-O-methyltransferase Gene Polymorphisms in Benign Prostatic Hyperplasia and Sporadic Prostate Cancer
Authors: Tanaka Yuichiro , Sasaki Masahiro , Shiina Hiroaki , Tokizane Takashi , Deguchi Masao , Hirata Hiroshi , Hinoda Yuji , Okayama Naoko , Suehiro Yutaka , Urakami Shinji , Kawakami Toshifumi , Kaneuchi Masanori , Pookot Deepa , Igawa Mikio , Okuyama Akihiko , Ishii Nobuhisa , Dahiya Rajvir
Published: March 2006

Various carcinogenic metabolites, including catechol estrogens, play a role in malignant transformation. An enzyme that is capable of neutralizing the genotoxic effects of these compounds is catechol-O-methyltransferase (COMT). A variant form of this enzyme has been shown to reduce its activity by up to 4-fold; thus, we hypothesize that single nucleotide polymorphisms of the COMT gene can be a risk factor for benign prostatic hyperplasia (BPH) and prostate cancer. To test this hypothesis, the genetic distribution of three different COMT polymorphisms at codon 62 (C→T), codon 72 (G→T), and codon 158 (G→A) were analyzed in 131 normal healthy subjects, 134 BPH, and 178 sporadic prostate cancer samples from a Japanese population. Results of these experiments show that the variant genotype at codon 62 (P = 0.060) and codon 158 (P = 0.047) are risk factors for prostate cancer but not BPH when compared with normal controls. Odds ratio (OR) and 95% confidence interval (95% CI) for cancer were 3.24 and 1.38 to 7.61, respectively, for codon 62 T/T genotype when compared with wild type. At codon 158, the A/A variant for cancer had an OR of 3.00 with a 95% CI of 1.38 to 6.54 compared with wild type. Codons 62 and 158 were in linkage disequilibrium (LD), and when compared with the C-G haplotype, other types (C-A, T-G, T-A) were observed to be associated with prostate cancer (P = 0.040) but not BPH. Codon 72 on the other hand, was not in LD with either codon 62 or 158. The homozygous variant on codon 72 was rare in this Japanese population, and the heterozygous G/T at this codon was not associated with either prostate cancer or BPH. When evaluating the risk of COMT polymorphisms with stage or grade of cancer, no associations were observed for any of the genotypes with the exception of a tendency (P = 0.096) for the variant A allele on codon 158 to be correlated with higher stages (≥T3) of cancer. This is the first report that shows the polymorphisms of COMT to be associated with sporadic prostatic carcinogenesis. These results are important in understanding the role of COMT polymorphisms in the pathogenesis of prostate cancer. (Cancer Epidemiol Biomarkers Prev 2006;15(2):238–44)
The Insulin-Like Growth Factor System and Mammographic Features in Premenopausal and Postmenopausal Women
Authors: dos Santos Silva Isabel , Johnson Nichola , De Stavola Bianca , Torres-Mejía Gabriela , Fletcher Olivia , Allen Diane S. , Allen Naomi E. , Key Timothy J. , Fentiman Ian S. , Holly Jeff M.P. , Peto Julian
Published: March 2006

High levels of circulating insulin-like growth factor-I (IGF-I) and its major binding protein (IGFBP-3) at premenopausal ages have been associated with an increased breast cancer risk. We conducted a cross-sectional study (215 premenopausal women and 241 after natural menopause) nested within the Guernsey prospective studies to examine the relationship between the IGF system and mammographic features of the breast. The mammographically dense area in the breast increased with increasing serum levels of IGF-I (P for linear trend, Pt = 0.05), IGF-II (Pt = 0.08), and IGFBP-3 (Pt = 0.01) only in premenopausal women. IGF-II and IGFBP-3 serum levels were associated with increases in the mammographically lucent area in both premenopausal (Pt = 0.01 and 0.04, respectively) and postmenopausal women (Pt < 0.001 for both), but these associations were no longer statistically significant after adjustment for body mass index and waist circumference. Neither the IGF-I/IGFBP-3 nor the IGF-II/IGFBP-3 molar ratio was associated with any of these mammographic features. The number of A alleles at a polymorphic locus in the promoter region of the IGFBP-3 gene was associated with increasing mean IGFBP-3 levels in both premenopausal (Pt = 0.01) and postmenopausal (Pt <0.001) women but not with mammographically dense area. These results support the hypothesis that the IGF system may affect the amount of mammographically dense tissue in premenopausal women, possibly by promoting cell proliferation and inhibiting apoptosis in the fibroglandular tissue. The findings also show strong relations between IGF-II and IGFBP-3 levels and the amount of mammographically lucent tissue, reflecting the associations between body adiposity and amount of fat tissue in the breast and between body adiposity and circulating levels of these growth factors. (Cancer Epidemiol Biomarkers Prev 2006;15(3):449–55)
GSTP1 and GSTA1 Polymorphisms Interact with Cruciferous Vegetable Intake in Colorectal Adenoma Risk
Authors: Tijhuis Mariken J. , Wark Petra A. , Aarts Jac M.M.J.G. , Visker Marleen H.P.W. , Nagengast Fokko M. , Kok Frans J. , Kampman Ellen
Published: March 2006

The possible interplay between cruciferous vegetable consumption, functional genetic variations in glutathione S-transferases (GST) M1, T1, P1, and A1, and colorectal adenomas, was investigated in a Dutch case-control study. The GSTM1 and GSTT1 deletion polymorphisms, and the single nucleotide polymorphisms in GSTP1 (A313G) and in GSTA1 (C-69T) were assessed among 746 cases who developed colorectal adenomas and 698 endoscopy-based controls without any type of colorectal polyps. High and low cruciferous vegetable consumption was defined based on a median split in the control group. High consumption was slightly positively associated with colorectal adenomas [odds ratio (OR) 1.15; 95% confidence interval, 0.92-1.44]. For GSTP1, a positive association with higher cruciferous vegetable intake was only apparent in individuals with the low-activity GSTP1 genotype (GG genotype, OR 1.94; 95% confidence interval, 1.02-3.69). This interaction was more pronounced in men, with higher age and with higher meat intake. The GSTA1 polymorphism may have a modifying role as well: the OR for higher intake compared with lower intake was 1.57 (0.93-2.65) for individuals homozygous for the low expression variant (TT genotype). This seemed to be stronger with younger age and higher red meat intake. Cruciferous vegetable consumption and the combined GSTA1 and GSTP1 genotypes showed a statistically significant interaction (P = 0.034). The GSTM1 and GSTT1 genotypes did not seem to modify the association between cruciferous vegetable intake and colorectal adenomas. In conclusion, GSTP1 and GSTA1 genotypes might modulate the association between cruciferous vegetable intake and colorectal adenomas. (Cancer Epidemiol Biomarkers Prev 2005;14(12):2943–51)
Effect of Physical Activity on Women at Increased Risk of Breast Cancer: Results from the E3N Cohort Study
Authors: Tehard Bertrand , Friedenreich Christine M. , Oppert Jean-Michel , Clavel-Chapelon Francoise
Published: March 2006

Purpose: There is a need to investigate the type, duration, frequency, and intensity of physical activity that are critical to reduce the risk of breast cancer, and if this relation differs among subgroups of women.

Methods: We analyzed the relation between physical activity and breast cancer incidence between 1990 and 2002 (n = 3,424 cases), among 90,509 women of the French E3N cohort, ages between 40 and 65 years in 1990. We gave special attention to effect modification by body mass index (BMI), family history of breast cancer, parity, and hormone replacement therapy (HRT).

Results: A linear decrease in risk of breast cancer was observed with increasing amounts of moderate (Ptrend < 0.01) and vigorous (Ptrend < 0.0001) recreational activities. Compared with women who reported no recreational activities, those with more than five weekly hours of vigorous recreational activity had a relative risk of 0.62 (0.49-0.78). This decrease was still observed among women who were overweight, nulliparous, had a family history of breast cancer, or used HRT. Compared with the whole cohort, among nulliparous women, the reduction of risk observed was of a higher magnitude, although the test for heterogeneity did not reach statistical significance.

Conclusion: A risk reduction of breast cancer was particularly observed with vigorous recreational activity. Further investigations are needed to confirm that intensity is an important variable to consider in risk reduction and to identify the precise biological mechanisms involved in such a risk reduction. (Cancer Epidemiol Biomarkers Prev 2006;15(1):57–64)
RNASELMutation Screening and Association Study in Ashkenazi and Non-Ashkenazi Prostate Cancer Patients
Authors: Orr-Urtreger Avi , Bar-Shira Anat , Bercovich Dani , Matarasso Noa , Rozovsky Uri , Rosner Serena , Soloviov Sonya , Rennert Gad , Kadouri Luna , Hubert Ayala , Rennert Hanna , Matzkin Haim
Published: March 2006

Epidemiologic and genetic studies support the considerable effect of heritable factors on prostate tumorigenesis, although to date, no unequivocal susceptibility gene has been identified. The extensive study of RNASEL in prostate cancer patients worldwide has yielded conflicting results. We reevaluated the role of the RNASEL 471delAAAG Ashkenazi founder mutation in 1,642 Ashkenazi patients with prostate, bladder, breast/ovarian, and colon cancers; Ashkenazi controls; and in non-Ashkenazi prostate cancer patients and controls. The entire RNASEL coding sequence was also screened using denaturing high-performance liquid chromatography and multiplex ligation–dependent probe amplification for possible sequence variations or copy number changes in a population of prostate cancer patients. The 471delAAAG mutation was detected in 2.4% of the Ashkenazi prostate cancer patients; in 1.9% of patients with bladder, breast/ovarian, and colon cancers; and in 2.0% of the Ashkenazi controls. Seven additional variants were detected in RNASEL, including a novel potentially pathogenic splice site mutation, IVS5+1delG, although none were associated with increased prostate cancer risk. Multiplex ligation–dependent probe amplification analysis showed two RNASEL gene copies in all 300 prostate cancer patients tested. We estimated that the RNASEL 471delAAAG founder mutation, which was detected in 2% of the Ashkenazi Jews, originated between the 2nd and 5th centuries A.D., compared with the less frequent (1%) BRCA1 185delAG founder mutation, which originated hundreds of years earlier. Taken together, our analysis does not support a role for the RNASEL 471delAAAG Ashkenazi mutation nor for the other alterations detected in RNASEL in prostate cancer risk in Jewish men. (Cancer Epidemiol Biomarkers Prev 2006;15(3):474–9)
Meat Consumption among Black and White Men and Risk of Prostate Cancer in the Cancer Prevention Study II Nutrition Cohort
Authors: Rodriguez Carmen , McCullough Marjorie L. , Mondul Alison M. , Jacobs Eric J. , Chao Ann , Patel Alpa V. , Thun Michael J. , Calle Eugenia E.
Published: March 2006

Previous epidemiologic studies have suggested that intake of red meat may be associated with increased risk of prostate cancer. Few studies, however, have examined these associations by race. We examined intake of red meat, processed meat, and poultry in relation to incident prostate cancer among Black and White men in the Cancer Prevention Study II Nutrition Cohort. Participants in the study completed a detailed questionnaire on diet, medical history, and lifestyle in 1992 to 1993. After excluding men with a history of cancer and incomplete dietary information, 692 Black and 64,856 White men were included in the cohort. During follow-up through August 31, 2001, we documented 85 and 5,028 cases of incident prostate cancer among Black and White men, respectively. Cox proportional hazards models were used to estimate rate ratios (RR) and 95% confidence intervals (95% CI). No measure of meat consumption was associated with risk of prostate cancer among White men. Among Black men, total red meat intake (processed plus unprocessed red meat) was associated with higher risk of prostate cancer (RR, 2.0; 95% CI, 1.0-4.2 for highest versus lowest quartile; Ptrend = 0.05); this increase in risk was mainly due to risk associated with consumption of cooked processed meats (sausages, bacon, and hot dogs; RR, 2.7; 95% CI, 1.3-5.3 for highest versus lowest quartile; Ptrend = 0.008). This study suggests that high consumption of cooked processed meats may contribute to prostate cancer risk among Black men in the United States.(Cancer Epidemiol Biomarkers Prev 2006;15(2):211–6)
How Well Do HapMap Haplotypes Identify Common Haplotypes of Genes? A Comparison with Haplotypes of 334 Genes Resequenced in the Environmental Genome Project
Authors: Taylor Jack A. , Xu Zong-Li , Kaplan Norman L. , Morris Richard W.
Published: March 2006

One of the goals of the International HapMap Project is the identification of common haplotypes in genes. However, HapMap uses an incomplete catalogue of single nucleotide polymorphisms (SNPs) and might miss some common haplotypes. We examined this issue using data from the Environmental Genome Project (EGP) which resequenced 335 genes in 90 people, and thus, has a nearly complete catalogue of gene SNPs. The EGP identified a total of 45,243 SNPs, of which 10,780 were common SNPs (minor allele frequency ≥0.1). Using EGP common SNP genotype data, we identified 1,459 haplotypes with frequency ≥0.05 and we use these as “benchmark” haplotypes. HapMap release 16 had genotype information for 1,573 of 10,780 (15%) EGP common SNPs. Using these SNPs, we identified common HapMap haplotypes (frequency ≥0.05) in each of the four HapMap ethnic groups. To compare common HapMap haplotypes to EGP benchmark haplotypes, we collapsed benchmark haplotypes to the set of 1,573 SNPs. Ninety-eight percent of the collapsed benchmark haplotypes could be found as common HapMap haplotypes in one or more of the four HapMap ethnic groups. However, collapsing benchmark haplotypes to the set of SNPs available in HapMap resulted in a loss of haplotype information: 545 of 1,459 (37%) benchmark haplotypes were uniquely identified, and only 25% of genes had all their benchmark haplotypes uniquely identified. We resampled the EGP data to examine the effect of increasing the number of HapMap SNPs to 5 million, and estimate that ∼40% of common SNPs in genes will be sampled and that half of the genes will have sufficient SNPs to identify all common haplotypes. This inability to distinguish common haplotypes of genes may result in loss of power when examining haplotype-disease association. (Cancer Epidemiol Biomarkers Prev 2006;15(1):133–7)
Interactions of Sequence Variants inInterleukin-1 Receptor–Associated Kinase4and theToll-Like Receptor 6-1-10Gene Cluster Increase Prostate Cancer Risk
Authors: Sun Jielin , Wiklund Fredrik , Hsu Fang-Chi , Bälter Katarina , Zheng S. Lilly , Johansson Jan-Erik , Chang Baoli , Liu Wennuan , Li Tao , Turner Aubrey R. , Li Liwu , Li Ge , Adami Hans-Olov , Isaacs William B. , Xu Jianfeng , Grönberg Henrik
Published: March 2006

Chronic or recurrent inflammation has been suggested as a causal factor in several human malignancies, including prostate cancer. Genetic predisposition is also a strong risk factor in the development of prostate cancer. In particular, Toll-like receptors (TLR), especially the TLR6-1-10 gene cluster, are involved in prostate cancer development. Interleukin-1 receptor-associated kinases (IRAK) 1 and 4 are critical components in the TLR signaling pathway. In this large case-control study, we tested two hypotheses: (a) sequence variants in IRAK1 and IRAK4 are associated with prostate cancer risk and (b) sequence variants in IRAK1/4 and TLR1-6-10 interacts and confers a stronger risk to prostate cancer. We analyzed 11 single nucleotide polymorphisms (four in IRAK1 and seven in IRAK4) among 1,383 newly diagnosed prostate cancer patients and 780 population controls in Sweden. Although the single-nucleotide polymorphisms in IRAK1 and IRAK4 alone were not significantly associated with prostate cancer risk, one single-nucleotide polymorphism in IRAK4, when combined with the high-risk genotype at TLR6-1-10, conferred a significant excess risk of prostate cancer. In particular, men with the risk genotype at TLR6-1-10 and IRAK4-7987 CG/CC had an odds ratio of 9.68 (P = 0.03) when compared with men who had wild-type genotypes. Our findings suggest synergistic effects between sequence variants in IRAK4 and the TLR 6-1-10 gene cluster. Although this study was based on a priori hypothesis and was designed to address many common issues facing this type of study, our results need confirmation in even larger studies. (Cancer Epidemiol Biomarkers Prev 2006;15(3):480–5)