bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 625: Flavonoid intake and risk of pancreatic cancer in the National Institutes of Health-AARP Diet and Health Study Cohort
Authors: Arem Hannah , Bobe Gerd , Sampson Joshua , Subar Amy F. , Park Yikyung , Risch Harvey , Hollenbeck Albert R. , Mayne Susan T. , Stolzenberg-Solomon Rachael
Published: August 2012

Flavonoids are the most common of the plant polyphenolics and are obtained from foods such as tea, citrus and other fruits. Laboratory and animal studies suggest that through anti-oxidant properties dietary flavonoids may reduce the risk of pancreatic cancer, and the few previous epidemiologic studies on flavonoid intake and pancreatic cancer risk have shown protective associations for specific types of flavonoids. We examined the association between total flavonoid intake, six flavonoid subgroups, flavonoid-rich foods and development of exocrine pancreatic cancer among 537,104 participants in the NIH-AARP Diet and Health Study with complete dietary data. Men and women aged 50 to 71 years completed a self-administered food frequency questionnaire at baseline (1995-1996) that ascertained diet and other lifestyle information. During follow-up through 2006 (median 10.6 years, max 11.2 years), 2379 incident pancreatic cancer cases were identified. Flavonoid intake was estimated from two databases developed from the USDA Nutrient Data laboratory. The distribution of flavonoid intake differed by sex (mean female intake 216 mg/day, range 0.41-9456; mean male intake 153 mg/day, range 0.95-6561); therefore, quintiles were based on sex specific cut-points. We used Cox proportional hazard models with age as the underlying time metric to calculate hazard ratios (HR) for pancreatic cancer. Models were adjusted for sex, smoking, diabetes, body mass index, alcohol use, and saturated fat and red meat intake. We found no association between total flavonoid intake (hazard ratio (HR)=1.09; 95% confidence interval (CI) 0.96-1.24) or the six flavonoid subgroups and risk of pancreatic cancer. Although there was no significant interaction by sex or smoking (p-interaction > 0.10), in stratified analyses we observed significant increased risks for total flavonoid intake among current smokers (Q5 versus Q1 HR=1.45, 95% CI 1.12-1.88, p-trend=0.002), while no such associations were evident among never (HR=1.01, 95% CI 1.00-1.03) or former smokers (HR=0.99, 95% CI 0.98-1.01). Among smokers flavonol and isoflavone intakes were positively associated with pancreatic cancer comparing extreme quintiles, with HRs =1.38 (95% CI 1.05-1.82, p trend=0.019) and 1.39 (95% CI 1.03-1.86, p trend=0.022) respectively. It is possible that exposures correlated to smoking but not accounted for in our analysis explain the observed associations. Our results do not support the hypothesis that flavonoid intake plays a protective role in pancreatic cancer carcinogenesis.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 625. doi:1538-7445.AM2012-625
Abstract 630: Tobacco smoking women are not at higher risk than men for lung cancer
Authors: Matteis Sara De , Consonni Dario , Pesatori Angela C. , Bergen Andrew W. , Bertazzi Pier Alberto , Caporaso Neil E. , Lubin Jay H. , Wacholder Sholom , Landi Maria Teresa
Published: August 2012

Background. Worldwide lung cancer incidence is decreasing or leveling off among men, but rising among women. Gender differences in the effect of tobacco carcinogens on lung cancer risk have been hypothesized, but the epidemiologic evidence is conflicting. Objective. To test gender-smoking interaction in the association with lung cancer risk within the large Environment And Genetics in Lung cancer Etiology (EAGLE) population-based case-control study, conducted in Italy between 2002-2005. The study collected detailed lifetime smoking histories by personal interview. Methods. Separately for males and females, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) for cumulative exposure to smoking (pack-years) by logistic regression, adjusted for age, residence area, and time since quitting smoking. We evaluated several potential confounders and effect-modifiers, including tobacco type, inhalation depth, percentage of each cigarette smoked, and visualized the tobacco dose-response relationship across genders through floating trends. We tested gender-smoking interaction (female versus male effect) by including their product term in the models. Results. When the model included never smoker cases and controls, ORs for categories of pack-years were higher in men, with a negative female-smoking interaction (P=0.0009). Within ever smokers, ORs estimates were somewhat higher in women, but the test for interaction was not significant (P=0.55). We obtained similar results for pack-years as a continuous (log-transformed) variable. Among smokers, no gender-smoking interaction was found by histology. Conclusion. Our findings do not support a higher female susceptibility to tobacco-related lung cancer. Equally vigorous health policy interventions should continue to fight smoking habits in both genders.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 630. doi:1538-7445.AM2012-630
Abstract 631: Association between dietary calcium intake and lung cancer risk in female non-smokers: A report from the Shanghai Women's Health Study
Authors: Takata Yumie , Shu Xiao Ou , Yang Gong , Li Honglan , Dai Qi , Gao Jing , Cai Qiuyin , Chow Wong-Ho , Gao Yutang , Zheng Wei
Published: August 2012

Calcium has been implicated in carcinogenesis, especially through cell signaling and cell cycle regulation. Previous epidemiologic studies reported associations of calcium intake with the risk of colorectal, breast or prostate cancer. However, the studies investigating the association with lung cancer risk are limited, particularly among non-smokers. We evaluated the association of dietary calcium and other minerals that affect the calcium absorption with the risk of incident lung cancer among female non-smokers in the Shanghai Women's Health Study, a population-based cohort study of 74,941 women aged 40-70 years at enrollment (March 1997 to May 2000). Included in this analysis were 71,267 women who had never smoked and no prior history of cancer at baseline. Dietary intake was assessed using a validated quantitative food frequency questionnaire administered in person by trained interviewers. Cancer incidence and vital status were ascertained through annual linkage to the Shanghai Cancer Registry and Shanghai Vital Statistics data bases and biennial home visits. This analysis included 428 incident lung cancer cases accrued among the cohort members between April 1998 and December 2009 after the study enrollment. Cox proportional hazard regression was used to calculate the risk of lung cancer by quartiles of intake of calcium, magnesium, phosphorus or the calcium to magnesium (Ca: Mg) or calcium to phosphorus (Ca: P) ratios and by the use of calcium supplement, while adjusting for age, total caloric intake, income, occupation, passive smoking, history of asthma and body mass index. Intakes of calcium and phosphorus and the Ca: Mg and Ca: P ratios were inversely associated with the lung cancer risk; the corresponding risk reduction at the highest quartile comparing with the lowest was 34% for calcium, 45% for phosphorus, 38% for the Ca: Mg ratio and 25% for the Ca: P ratio (p for trend = 0.007, 0.02, 0.003 and 0.03, respectively). Calcium supplement was also associated with 33% significantly decreased risk. No association was observed for dietary magnesium intake (p for trend = 0.51). Our study provides one of the first evidence suggesting a possible role of calcium in lung cancer prevention among female non-smokers.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 631. doi:1538-7445.AM2012-631
Abstract 636: Non-melanoma skin cancer and risk of second primary cancer
Authors: Song Fengju , Qureshi Abrar , Giovannucci Edward , Fuchs Charlie , Chen Wendy , Stampfer Meir , Han Jiali
Published: August 2012

Objective: Previous studies suggest a positive association between history of non-melanoma skin cancer (NMSC) and risk of subsequent cancer development. We prospectively investigate this association in both men and women. Methods: In two large cohorts in the US, the Health Professionals Follow-up Study (HPFS) and the Nurses’ Health Study (NHS), we prospectively examined the risks of primary cancer according to history of NMSC. In the HPFS, 876,094 person-years were followed up from June 1986 to June 2008. In the NHS, 2,358,185 person-years were followed up from June 1984 to June 2008. We documented 30,636 cancer cases after ongoing NMSC diagnosis. The median time (and range) of diagnosis between NMSC and subsequent cancer was 156 (3 - 342) months in the NHS, and 116 (3 - 259) months in the HPFS. Cox proportional hazard models were used to calculate relative risks (RRs) and 95% confidence intervals (CIs), adjusting for major cancer risk factors (e.g. age, smoking, body mass index, physical activity, etc). Results: A history of NMSC was associated with a higher risk of other primary cancers in men (RR = 1.15; 95% CI: 1.08, 1.21; P < 0.0001), and in women (RR = 1.25; 95% CI: 1.20, 1.31; P < 0.0001). For individual cancer sites, in men, a history of NMSC was associated with an increased risk of prostate cancer, non-Hodgkin lymphoma, and melanoma. In women, a history of NMSC was associated with an increased risk of breast cancer, endometrial cancer, ovarian cancer, lung cancer, non-Hodgkin lymphoma, renal cancer, melanoma, and oral cancer. Conclusions: Our prospective-cohort study provides evidence for an association between a history of NMSC and an increased risk of subsequent malignancies. Further studies are warranted to identify the potential mechanism underlying this relationship.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 636. doi:1538-7445.AM2012-636
Abstract 637: Dietary heme iron and risk of colorectal cancer with specific mutations in colorectal cancer key genes
Authors: Gilsing Anne , Fransen Fiona , de Kok Theo M. , Goldbohm Alexandra R. , de Bruine Adriaan P. , van Engeland M , van den Brandt Piet A. , de Goeij Anton F. , Weijenberg Matty P.
Published: August 2012

Background: Red meat intake has been linked to increased colorectal cancer risk but the underlying mechanisms remain unclear. Experimental studies suggest a role for dietary heme, but epidemiological evidence for its carcinogenic potential is inconclusive. Because heme may promote specific mutations, it could be insightful to link heme exposure data to colorectal cancer (CRC) with such mutations in key genes in an observational, population-based study. Methods: We investigated the association between dietary heme iron intake (tertiles) and CRC cancer with adenomatous polyposis coli (APC) and Kirsten ras (KRAS) mutations, and tumor protein 53 (TP53) overexpression, in the Netherlands Cohort Study. After 7.3 yrs of follow-up, excluding the first 2.3 years, adjusted rate ratios (RR) and 95% confidence intervals (CI) were calculated, using 3,949 subcohort members (aged 55-69 years at baseline) and 733 CRC patients. Results: Heme iron intake was associated with an increased risk of CRC with activating G>A mutations in KRAS (RR=2.14 for the highest compared to the lowest intake; 95% CI: 1.17, 3.92; Ptrend = 0.01). In addition, a positive association between heme intake and the risk of overall G>A mutations in APC tumors was observed (RR=1.73 for the highest compared to the lowest intake; 95% CI: 1.18, 2.54; Ptrend = 0.005). However, this association was not found when restricting our analyses to CRC harboring G>A mutations leading to a truncated APC (RR=1.35 for the highest compared to the lowest intake; 95% CI: 0.79,2.37; Ptrend = 0.29). Moreover, there was a positive association between heme iron intake and the risk of P53 overexpressed tumors which was not observed in tumours without P53 overexpression (Pheterogeneity = 0.08). Conclusion: These results suggest that heme iron intake is associated with an increased risk of colorectal tumors harboring G>A transitions in KRAS and to a lesser extend in APC, and overexpression of P53. Taking CRC heterogeneity into account contributes to a better molecular understanding of the established association between red meat intake and CRC.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 637. doi:1538-7445.AM2012-637
Abstract 640: Age of menarche and height as adolescent growth in relation to breast cancer risk
Authors: Choi Ji-Yeob , Jeon Sujee , Park Sue K. , Noh Dong-Young , Ahn Sei-Hyun , Yoo Keun-Young , Kang Daehee
Published: August 2012

Age of menarche as well as height is known to be associated with breast cancer risk. Adult height is associated with age at menarche, which may explain that growth in height accelerates driven by hormone changes during adolescence. The authors evaluated associations between the age of menarche and height as the adolescent growth indicator and breast cancer risk among 3,725 cases and 3,748 controls enrolled in a multicenter, case-control study in Korea, Seoul Breast Cancer Study (2001-2007). Logistic regression models were used to estimate odds ratios (ORs) of age at menarche (<=13, 14-15, and 16+ years) and quintile of height calculated in each 10-year age group based on total participants for breast cancer risk. The associations were assessed in overall and in strata of menopausal status, birth year group (median, 1957) and hormone receptor status. Early menarche and taller height increased risk of breast cancer as expected; for both premenopausal and postmenopausal women, those starting menarche at 13 years or younger had 1.3-fold (95% CI: 1.1-1.6 for premenopausal women and 1.0-1.7 for postmenopausal women, respectively) comparing to women starting menarche at 16 years or older. In contrast, the association between height and breast cancer risk was different between menopausal status; women with 5th quintile in each age group had 2.1-fold (95% CI: 1.6-2.7) comparing to women with 1st quintile among postmenopausal women, however, associations were absent among premenopausal women. Age at menarche, height and birth year were highly correlated with each other; age at menarche and height increased as the birth year increased significantly. The associations of age at menarche and height on breast cancer in the strata of birth year group were similar with the associations in the menopausal status. Although cases with hormone receptor positive increased as the birth year increased, the ORs of age at menarche and height did not vary significantly by hormone receptor status. These findings suggest that age at menarche and adult height is associated with breast cancer overall, particularly among postmenopausal women or women born prior to 1957. This may result from the chronological changes of adolescent growth in Korea.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 640. doi:1538-7445.AM2012-640
Abstract 648: Tobacco assessment in actively accruing Cooperative Group clinical trials
Authors: Warren Graham W. , Peters Erica N. , Torres Essie , Cummings K. Michael , Gritz Ellen R. , Hyland Andrew , Herbst Roy , Marshall James R. , Toll Benjamin A.
Published: August 2012

Purpose: The lack of accurate prospective tobacco assessments in cancer patients limits the ability to provide tobacco cessation and to accurately evaluate the true impact of tobacco use on cancer treatment outcomes. The purpose of this study was to evaluate tobacco use assessment in patients enrolled in actively accruing cancer clinical trials. Methods: Protocols and forms for 155 actively accruing trials in the NCI's Clinical Trials Cooperative Group program were evaluated for detailed tobacco use assessment at enrollment and through follow-up using a structured coding instrument. Results: Of the 155 clinical trials reviewed, the mean accrual start date was 2008.6 (range 2003-2011), 74.1% were phase III trials, and the total potential accrual population was 106,985 patients. Any form of tobacco use (i.e., cigarette, pipe, cigar, smokeless tobacco, or unspecified “tobacco”) was assessed in 29% of trials (46% of total patient accrual) at enrollment. Current cigarette use at enrollment was assessed in 21.9% of trials and former cigarette use was assessed in 21.3% of trials. Only 4.5% of trials assessed any form of tobacco use during follow-up. Secondhand smoke exposure was captured in 2.6% of trials at enrollment and only 1 trial during follow-up. None of the trials assessed nicotine dependence or interest in quitting at any point during enrollment or treatment. Tobacco assessment varied by type of cancer with a higher proportion of patients being assessed in lung or head and neck cancer trials. Conclusion: Most actively accruing cooperative group clinical trials do not assess tobacco use. Failure to incorporate standardized tobacco assessments into funded national clinical trials will continue to limit the ability to provide evidence based cessation support and will limit the ability to accurately understand the precise impact of tobacco use on cancer treatment outcomes.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 648. doi:1538-7445.AM2012-648
Abstract 654: The effect of lung cancer screening awareness on smoking behavior among U.S. adults
Authors: Thompson Dianne N. , Barrett Richard A. , Deonarine Anand , Williams Carla D. , White-Coleman Debra , Thomas Alicia , Horton Sara , Cross Amanda J. , Laiyemo Adeyinka O.
Published: August 2012

Background: Emphasizing the risk of lung cancer can encourage smoking cessation, but use of spiral low-dose CT scans reduced lung cancer mortality in a recent randomized screening trial. It is unknown if awareness of lung cancer screening will influence smoking behavior. Aim: To evaluate the awareness of lung cancer screening and to determine if awareness of lung cancer screening affects smoking cessation-related behavior among current smokers. Methods: We identified 7,282 adult respondents who answered questions concerning their smoking-related behavior in the 2007 Health Information National Trends Survey (HINTS). We used logistic regression models to evaluate the association of smoking status with awareness of lung cancer screening and we also investigated the association of lung cancer screening awareness with smoking cessation behaviors among current smokers. Results: The mean age of responders was 54.1 years and 61.2% were females. There were 3,813 (52.4%) never smokers; 2,222 (30.5%) former smokers; and 1,247 (17.2%) current smokers. Overall, 2,183 (30.6%) of respondents had heard of a lung cancer screening test (29.6% never smokers, 33.4% former smokers, and 28.5% current smokers; P value = 0.002). Chest X-ray (64.4%) and CT scan (5.7%) were among the screening tests that they have heard of. Among current smokers, awareness of lung cancer screening had no effect on smoking cessation behavior after adjusting for age, sex, race, education, income and marital status (Table). Conclusion: Awareness of lung cancer screening tests did not affect smoking cessation behavior of current smokers. However, smoking cessation should be recommended for all current smokers and those with a history of smoking should be informed about lung cancer screening with CT scan.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 654. doi:1538-7445.AM2012-654
Abstract 655: Menopausal hormone therapy and breast cancer risk: The CECILE Study
Authors: Cordina-Duverger Emilie , Truong Thérèse , Anger Antoinette , Mulot Claire , Arveux Patrick , Kerbrat Pierre , Menegaux Florence , Guenel Pascal
Published: August 2012

Breast cancer in post-menopausal women has been associated with the use of menopausal hormone therapy (MHT). Estrogen-only (EO) and combined estrogen-progestagen (EP) therapies have been evaluated as potentially carcinogenic to human by the IARC. However, the type of estrogen and progestagen in the MHT varies considerably by country. For example, besides synthetic progestagens, the use of natural progesterone in combined EP therapy is specific to France. We investigated whether the association between MHT and breast cancer in postmenopausal women differ by type of chemical compound. We conducted a population-based case-control study in France in 762 cases and 840 controls recruited among postmenopausal women in two French “départements”. Data were collected including name of medication, date of start and end of each medication used. Unconditional logistic regression models were used, with adjustment for age, study area, and known risk factors for breast cancer. We observed a significant increased risk of breast cancer for current users of estrogen plus synthetic progestagen while no association was found for any use of estrogen-only therapy or combined therapy of estrogen plus natural progesterone. Among current users of estrogen plus synthetic progestagen, the association with breast cancer increased with duration of use and was higher in women who started their treatment before or shortly after menopause. Our study suggests that the use of natural progesterone as the progestagen component in a combined EP therapy is not associated with an increased risk of breast cancer. This result reinforces the findings reported in another cohort study of French women (E3N).

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 655. doi:1538-7445.AM2012-655
Abstract 658: Fruit and vegetable intake and cancer incidence in Korean men
Authors: Lee Jung Eun , Kim Dong-Hyun , Ahn Yoon-Ok
Published: August 2012

Few prospective cohort studies have examined the association between fruit and vegetable intake and cancer incidence in Asian population, who consume a diet rich in fruit and vegetable and experience dramatic change in their diet. We investigated whether total fruit intake, total vegetable intake, and total fruit and vegetable intake were associated with risk of incident cancers among 13,563 Korean men during 15 years of follow-up. We used the Cox proportional hazards model to calculate relative risks (RRs) and 95% confidence intervals (CIs) for incident cancers according to fruit and vegetable intake assessed by a validated food frequency-questionnaire. All statistical tests were two-sided. We identified a total of 831 incident cancers. We observed that low intake of total vegetable intake or total fruit and vegetable intake was associated with increased risk of overall cancer incidence. The risk reduction was attributable to increasing intake above a threshold of approximately 100 to 150 g/d. For example, compared with <100 g/d of total fruit and vegetable intake, RRs (95% CIs) for overall cancer risk were 0.74 (0.53-1.02) for 100-<300 g/d, 0.73 (0.53-1.01) for 300-<500 g/d, 0.76 (0.53-1.11) for 500-<600 g/d, and 0.71 (0.51-0.99) for 600 or more g/d. However, when we chose <200 g/d as the referent category, we did not observe the statistically significant associations. In conclusion, our findings suggest that low levels of fruit and vegetable intake could pose an increase in risk of cancer, but the risk could be minimized with modestly increasing intake.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 658. doi:1538-7445.AM2012-658
Abstract 671: Smoking, alcohol consumption and body size measures and risk of B-cell non-Hodgkin lymphoma among women in Los Angeles
Authors: Lu Yani , Wang Sophia , Sullivan-Halley Jane , Cozen Wendy , Bernstein Leslie
Published: August 2012

Background: There are few known causes for non-Hodgkin lymphoma (NHL). The aim of this study is to identify if previous suggested modifiable risk factors (smoking, alcohol consumption and body size measures) are associated with B-cell NHL risk among women. Methods: We conducted a population-based case-control study among women in Los Angeles County consisting of 998 histologically confirmed B-cell NHL patients and 998 individually matched controls (matched on age, race and socioeconomic status). Conditional logistic regression was used to evaluate these associations. Results: Compared to never smokers, current smokers had 51% increased risk of B-cell NHL (odds ratio [OR] =1.51, 95% confidence interval [CI] =1.10-2.09). The risk of B-cell NHL increased with increasing smoking years (P-trend=0.03) and pack-years (P-trend=0.02). This risk pattern was observed for diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, and mantle cell lymphoma although these associations were not statistically significant. Current alcohol consumption decreased B-cell NHL risk (OR=0.75, 95% CI=0.60-0.94) with risk most pronounced among women with moderate lifetime consumption (1-<7 drinks/week). Women who were obese at 5 years before diagnosis had an increased risk of B-cell NHL (OR=1.70, 95% CI=1.28-2.26). Among NHL subtypes, the increased risk was most pronounced for B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (OR=1.94, 95% CI=1.07-3.52). Conclusions: These findings add to the literature regarding the potential importance of modifiable risk factors and NHL risk. Our results suggest that smoking and obesity may increase NHL risk, but moderate alcohol consumption may reduce NHL risk.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 671. doi:1538-7445.AM2012-671
Abstract 681: Prognostic role of Perp in breast cancer
Authors: Dolfi Sonia C. , Kulkarni Diptee , Lu Shou-En , Chen Chunxia , Moore Dirk , Vazquez Alexei , Harris Sandi , Toppmeyer Deborah , Levine Arnold , Hirshfield Kim M.
Published: August 2012

Perp, a tetraspan plasma membrane protein, is activated by p53 during apoptosis and is also regulated by p63 where it functions as an essential component of the desmosome and contributes to epithelial integrity. A single nucleotide polymorphism (SNP) in Perp was identified by its effect on apoptotic efficiency in irradiated lymphoblastoid cell lines. Therefore, this SNP may have functional significance in clinical outcomes of cancer. In this study, this SNP in PERP was evaluated as a prognostic marker and in its relationship to other known prognostic factors. Genotyping was performed on DNA isolated from peripheral blood of 1020 patients with breast cancer and genotypes were linked with annotated clinical information. Analysis of recurrence free survival was performed on a subset limited to 790 Caucasians. Among Caucasian cases, homozygous SNP genotypes were nearly equally distributed (AA: 25% and GG: 26%). Using a COX proportional hazards survival analysis, the AA genotype was found to be an independent predictor of worse recurrence-free survival (RFS, hazard ratio [HR]: 1.95, 95% CI: 1.38-2.76, p=0.0001). RFS was similar between AG and GG carriers and was more favorable as compared to AA carriers. For patients receiving breast-conserving surgery followed by radiation, patients diagnosed at or above 51 years of age or patients with stage III disease, the deleterious effect of AA genotype on RFS was more significant. In addition, the AA genotype associated with decreased RFS in subgroups of Caucasian cases regardless of stratification by hormone receptor status, HER2 status, and whether they received chemotherapy or hormonal therapy. Adjusting for effects due to stage and chemotherapy, this association remained significant in estrogen receptor positive and progesterone receptor negative cases. We also analyzed the NCI-60 cell line panel for an association between this polymorphism and response to 132 standard chemotherapeutic drugs. A significant association was observed with respect to genotype and response to anti-mitotic agents. Collectively, cell lines with the AA genotype were more sensitive to anti-mitotic agents than the GG genotype. Clinical data suggest that the AA genotype of Perp has a functional phenotype leading to increased risk of recurrence. Further studies are needed to determine the mechanism behind this association, but ultimately this SNP may be useful as a prognostic marker in breast cancer and could be used as a tool to optimize treatment strategies.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 681. doi:1538-7445.AM2012-681
Abstract 684: Identification of biomarker genes associated with endocrine therapy responsiveness in patients with estrogen receptor positive IBC and nIBC
Authors: Van Laere Steven J. , Jansen Maurice PHM , Sas Leen , Sieuwerts Anieta , Vermeulen Peter B. , Berns Els MJJ , Dirix Luc Y.
Published: August 2012

Introduction: Endocrine therapy is a cornerstone in the treatment of patients with Estrogen Receptor (ER) positive (+) breast cancer. Nevertheless, resistance to endocrine treatment, either de novo or acquired, irreversably develops. In this study, we build upon the endocrine therapy resistant phenotype of patients with ER+ Inflammatory Breast Cancer (IBC) to identify and validate predictive biomarkers of endocrine therapy responsiveness. Materials and methods: Expression profiles of 21 ER+ IBC and 42 non-stage matched ER+ nIBC samples were compared using Prediction Analysis of Microarrays. The resulting gene signature was applied onto expression datasets from ER+ nIBC patients with documented intervals of relapse-free survival (RFS) for adjuvant endocrine treatment (GSE17705; N=298) or of progression-free survival (PFS) for first-line endocrine treatment (Jansen dataset (JCO, 2005), N=101). The gene signature classified samples as “IBC-like” or “nIBC-like” and Kaplan Meier and Cox regression analyses were performed. Robust biomarkers for endocrine resistance were selected using permutation analysis and validated using qRT-PCR on a series of samples from 225 ER+ nIBC patients with metastatic disease receiving first-line tamoxifen. Results: We identified a gene signature of 139 unique genes able to discriminate ER+ IBC from ER+ nIBC samples (sensitivity: 100%; specificity: 87.5%). Application of this signature onto data sets of patients with ER+ nIBC revealed significant associations with RFS (HR=1.87, P=0.001) and PFS (HR=2.04, P<0.001) under endocrine therapy. Permutation analysis selected 6 genes robustly discriminating ER+ IBC from ER+ nIBC samples: ABAT, ADAMDEC1, CLEC7A, ETS1, ITK1 and STC2. Expression analysis with qRT-PCR confirmed the predictive value of ADAMDEC1 (HR=1.127, P=0.020), ABAT (HR=0.779, P<0.001) and STC2 (HR=0.866, P<0.001) in 225 patients with ER+ breast cancer treated with Tamoxifen. Ingenuity Pathway Analysis revealed an intricate network linking each of the core genes with ER-, NFkB- and TGFβ-signalling. Conclusion: In this study we identified and validated a gene signature predictive of response to endocrine therapy in patients with breast cancer by comparing ER+ IBC samples to ER+ nIBC samples. Within this gene signature, ADAMDEC1, ABAT and STC2 were identified as robust markers for endocrine therapy responsiveness.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 684. doi:1538-7445.AM2012-684
Abstract 686: Warburg effect in mammary atypia from high-risk women
Authors: Seewaldt Victoria L. , Hoffman Abigail , Ibarra-Drendall Catherine
Published: August 2012

Background: Aggressive cancers are known to consume glucose avidly and produce lactic acid (rather than fully metabolize glucose via the Tricarboxylic Acid (TCA) cycle). This shift toward lactate production, even in the presence of adequate oxygen, is termed the Warburg effect. The Warburg effect is thought to be a late event in breast cancer, however, our studies in high-risk women provide evidence that the Warburg effect occurs during cancer initiation. This is an important observation as glucose-signaling can be readily targeted for breast cancer prevention with minimal toxicity. Here we investigated the role of the Warburg effect in breast cancer initiation in young high-risk women. Methods and Results: Similar to fluorodeoxyglucose, 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG) is a fluorescent glucose analog that can be used to track glucose uptake and glycolysis. 2-NBDG spectroscopy provides a means to track glucose metabolism in live mammary epithelial cells from high-risk women. We used 2-NBDG spectroscopy to measure glucose uptake in ER- breast cancer and live atypical mammary epithelial cells from high-risk premenopausal women. We observe that both triple-negative breast cancer and a subset of atypia exhibits accumulation of 2-NBDG. There is growing recognition that phosphoprotein signaling networks (rather than single genes) play a key role in breast cancer initiation and progression. Our team used Reverse Phase Proteomic Microarray (RPPM) profiling to test for activation of phosphoprotein signaling networks in atypical RPFNA cytology from high-risk premenopausal women in our cohort. RPFNA were obtained from two independent sets of 39 and 38 high-risk premenopausal women; 45% of these women were African American. The signaling network most highly expressed in precancerous cells contained activated signaling proteins associated with the Warburg effect (AKT/mTOR/PI3K), insulin signaling (pACC, IRS1) and epithelial to mesenchymal transition (EMT) IL6/Stat3/vimentin. Conclusions: This is the first evidence that abnormal glucose uptake and the Warburg effect occurs during breast cancer initiation in high-risk premenopausal women. These studies demonstrate our ability to identify abnormal glucose and activated signaling networks associated with the Warbug effect in atypical mammary cells from high-risk women.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 686. doi:1538-7445.AM2012-686
Abstract 689: Validation of antibodies to Estrogen Receptor ≤ and quantitative assessment of ERα1 and ERα5 expression in breast cancer
Authors: Wimberly Hallie , Murphy Leigh C. , Haffty Bruce , Rimm David
Published: August 2012

INTRODUCTION: Estrogen receptors are members of the nuclear hormone receptor family that play an important role in breast carcinogenesis and response to endocrine therapy. Though the role of ERα in breast cancer has been studied extensively, little is known about the alternative isoform ERα. ERα has significant sequence homology to ERα but is located on a different chromosome and maintains both overlapping and unique functional attributes. Five variants resulting from alternative splicing of the C-terminal region of ERα exist. The relevance of ERα variants in breast cancer outcomes and response to therapy is difficult to assess because of conflicting results in the literature, likely due to variable methods used to assess ERα in patient tumors. METHODS: Antibodies against ERα variants (ERα1: ThermoScientific PPG5/10; ERα2/cx: Serotec Clone 57/3; ERα5: Serotec Clone 5/25) were validated for staining specificity by siRNA knockdown of ESR2 as well as staining reproducibility on FFPE tissue by quantitative immunofluorescence (QIF) using AQUA technology (HistoRx). QIF staining of validated antibodies was then assessed on two separate breast cancer cohorts. RESULTS: ERα1 and ERα5, but not ERα2/cx, antibodies were found to be sensitive, specific and reproducible, as shown by reduction in signal after siRNA knockdown in cell lines and reproducible QIF scores on a set of breast cancer control cases. ERα1 and ERα5 expression is significantly associated in both cohorts examined (R*2=.224, p<0.0001). However, ERα1 does not show significant association with patient outcome or response to endocrine therapy. In contrast, ERα5 is associated with worse recurrence free survival (log rank p=0.0500) and, though it shows no association with response to tamoxifen, it predicts response to chemotherapy (log rank p=0.0393). CONCLUSIONS: Validation of ERα antibodies reveals that not all reagents are specific for the expected isoforms. Assessment of breast cancer cohorts using validated reagents show that ERα1 is not associated with outcome while ERα5 is both prognostic and predictive.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 689. doi:1538-7445.AM2012-689
Abstract 694: Characterization of a novel monoclonal antibody to Glia maturation factor-beta showing significant clinical utility in the identification of breast carcinoma
Authors: Alper Ozgul M. , Chen Cui P. , Akoa Achille , Herrmann Marille , Alper Ozge
Published: August 2012

Background: Glia maturation factor beta (GMF-beta) is a growth and differentiation factor of brain cells, stimulation of neural degeneration and inhibition of proliferation of tumor cells. It was recently found to involve in the progression of serous ovarian carcinoma. In the present study, we generated a novel antibody against human GMF-beta and investigated the potential of GMF-beta as a biomarker in breast cancer. Methods and findings: We generated a novel monoclonal antibody (mAb), AB-GMF-beta using hybridoma technology and native protein as an immunogen. This mAb is of IgG1 (kappa) type. It specifically recognized both native and denatured human GMF-beta protein and displayed high affinity as assessed by ELISA, immunohistochemistry assay, western blot and flow cytometry applications. Using this mAb in competitive ELISA, we showed for the first time that soluble GMF-beta level is significantly increased in metastatic breast cancer patients’ plasma which directly correlated with GMF-beta expression pattern in metastatic breast cancer tissues. Tissue expression of GMF-beta was determined by using immunohistochemical techniques. Seventy normal and 241 breast cancer tissues were included which consist of 194 ductal and 47 lobular carcinoma samples. Most of normal tissues showed negative or weak nuclear staining, while different levels of nuclear, and diffuse and weak cytoplasmic staining were observed in cancer sections. To evaluate the immunoreactivity of GMF-beta associated with tumor histological types, the staining intensity in nucleus were scored as 0, 1+, 2+ and 3+. Grade 0 and 1+ were defined as negative and 2+ and 3+ as positive. Forty four percent of ductal carcinomas showed strong staining whereas it is significantly increased to 72.3% in lobular tumors (p<0.001). Conclusion: The novel AB-GMF-beta mAb showed high performance in blood and tissue assays. The circulating GMF-beta levels and expressions in breast tissues are significantly increased in breast cancer patients in comparison of normal controls. The increased tissue expressions in breast carcinoma associate with histological tumor types. Our data suggest the potential clinical use of GMF-beta as a biomarker for diagnosis and prognosis in blood and tissue as well as a therapeutic target.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 694. doi:1538-7445.AM2012-694
Abstract 696: Loss of ALCAM function as a biologic basis for ethnic disparity in breast cancer
Authors: Tan Fang , Mosunjac Marina , Adams Amy L. , Ofori-Acquah Solomon
Published: August 2012

Breast cancer affects African American women at a lower frequency than Caucasian women, yet progression of the tumor and mortality from the disease is higher among African Americans. The genetic and molecular contributions to this ethnic disparity are poorly understood. Activated leukocyte cell adhesion molecule (ALCAM) is a junctional adhesive molecule tethered at sites of cell-cell contact in epithelia, mesenchymal, neuronal, and connective tissues. Loss of ALCAM function, due to reduced transcript levels, and low membrane localization, is associated with increased mortality, and poor response to adjuvant therapy in breast cancer. In the current study, we tested the hypothesis that this phenomenon contributes to the ethnic disparity in breast cancer in the US. We studied cases of breast cancer in Atlanta among African American (n=90) and Caucasian (n=104) women. Immunohistochemical staining was used to study ALCAM expression in tumor and non-tumor adjacent breast tissues. Clinicopathological variables including histologic tumor grade, tumor size, lymph node involvement, estrogen receptor (ER), progesterone receptor (PR), and HER2-neu status were abstracted, and their relationship to ALCAM expression was analyzed. Membranous ALCAM (mALCAM) expression correlated significantly with tumor grade, with poorly differentiated tumors showing low ALCAM staining. In addition, mALCAM correlated positively with ER status (African American: p=0.0013; Caucasian: p=0.0008) and PR status (African American: p=0.025; Caucasian: p=0.0027) in both ethnic groups; however, there were no associations between ALCAM expression and tumor size, lymph node involvement, or HER2-neu status. Tumor expression of mALCAM in Caucasians was significantly higher than in African Americans (p<0.0001), while there was no difference in expression of cytoplasmic ALCAM between the two groups. To our knowledge, this is the first study to examine ALCAM expression in African American breast cancer, and to compare this phenotype with Caucasians. Our results indicate that markedly lower ALCAM expression may contribute to the poor prognosis of breast cancer among African Americans. Future studies will examine the genetic basis of this variation.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 696. doi:1538-7445.AM2012-696
Abstract 699: The prognostic value of DNA polymerase ≤ for breast cancers
Authors: Liu Xiyong , Zhang Hang , Loera Sofia , Huang Yasheng , Deng Xutao , Liu Zheng , Zhang Suzhan , Chen Lirong , Zheng Shu , Chu Peiguo , Chou Kai-Ming , Yen Yun
Published: August 2012

DNA polymerase eta (Pol β, POLH) is a eukaryotic DNA polymerase involved in DNA repair by translesion synthesis. To address whether Pol ≤ impacts breast cancer survival, we conducted a retrospective outcome study on 145assessable cases of breast cancers collected from affiliated hospital of Zhejiang University (ZJU set). The results were validated on six published microarray data sets (1,154 cases) with pathoclinical and follow-up information. In the ZJU set, the protein levels of Pol ≤ were determined by IHC. The specificity of antibody against Pol ≤ was validated by using peptide blocking assay. It was shown that protein expression level of Pol ≤ positively correlates with cell proliferative marker Ki-67 (trends P=0.019). The Kaplan-Meier analysis revealed that Pol ≤ was significantly related that better overall survival in breast cancer patients who received chemotherapy or radiotherapy (Log rank p=0.003). Multivariate COX analysis further confirmed that the hazard ratio (HR) of Pol ≤ for overall and progress-free survival were 0.23(95% CI 0.05-0.95) and 0.32(0.11-0.96). Further stratification analysis demonstrated that Pol ≤ prognoses better survival in Luminal A and B molecular subtypes (HR=0.155 95% CI 0.04-0.62), but not HER 2 Positive or Triple negative breast cancer. Above findings were further validated in public microarray database. In Ivshina's dataset, the increase of POLH mRNA was significantly and negatively related with lymphnode involvement in a dose-dependent manner (trend p=0.044). The Kaplan-Meier analysis also revealed that the mRNA levels of POLH was significantly related to progress-free survival of breast cancer. In Chin's data, multivariate COX analysis also revealed that the HR increased significantly as with increase of POLH mRNA levels (HR= 0.22 95% CI 0.03-0.86, highest quartile vs. lowest quartile). Above findings suggested that the protein and mRNA expression levels of Pol ≤ prognoses better survival in breast cancer, especially in Luminal A or B breast cancers.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 699. doi:1538-7445.AM2012-699