Faculty Publications

Objective: Whether dietary patterns, rather than single foods or nutrients, are associated with breast density is not known. We investigated this in the Minnesota Breast Cancer Family Study. Methods: Participants completed a 153-item food frequency questionnaire and provided screening mammograms for breast density assessment using a computer-assisted method. We used multivariate linear regression to quantify dietary pattern-breast density associations. Results: Among 3,147 women with dietary information, three dietary patterns emerged from principal components analysis: a fruit-vegetable-cereal pattern, a salad-sauce-pasta/grain pattern, and a meat-starch pattern. Among 1,286 women with breast density estimates, the fruit-vegetable-cereal and salad-sauce-pasta/grain patterns were inversely associated with percent breast density only in stratified analyses. The fruit-vegetable-cereal pattern was inversely associated with breast density among premenopausal women (beta = -0.13, p = 0.09; interaction p = 0.009) and current smokers, (beta = -0.30, p = 0.02; interaction p = 0.05), while the salad-sauce-pasta/grain was inversely associated with breast density among current smokers (beta = -0.27, p = 0.06; interaction p = 0.006). Conclusion: Overall our results do not provide strong evidence for associations of dietary patterns with breast density. Suggestive inverse associations for the fruit-vegetable- cereal and salad-sauce-pasta/grain dietary patterns among smokers are consistent with previous reports and leave open the possibility that some dietary patterns influence breast density in population subsets. Nevertheless, these findings require confirmation, and their underlying reasons have yet to be clarified. (PsycINFO Database Record (c) 2009 APA, all rights reserved) (journal abstract).

We examined associations of dietary patterns with colon cancer risk in African Americans and Whites from a case-control study in North Carolina. Incident colon cancer cases, 40 to 80 yr (n = 636), and matched controls (n = 1,042) were interviewed in person to elicit information on potential colon cancer risk factors. A validated food frequency questionnaire adapted to include regional foods captured diet over the year prior to diagnosis (cases) or interview date (controls). Three meaningful intake patterns were identified in both Whites and African Americans: Western-Southern, fruit-vegetable, and metropolitan. Compared to the Western-Southern pattern, the fruit-vegetable and metropolitan patterns were associated with more healthful dietary behaviors (e.g., higher vegetable intake and lower red meat consumption), and demographic/lifestyle characteristics typically correlated with low colon cancer risk, for example, lower BMI, higher education, and higher NSAID use. The fruit-vegetable pattern was significantly inversely associated with colon cancer risk in Whites (OR = 0.4, 95% CI = 0.3-0.6) and the metropolitan pattern with a nonsignificant 30% risk reduction in both Whites and African Americans after adjustment for education. The Western-Southern pattern was not associated with colon cancer risk. These findings may explain some of the racial differences in colon cancer incidence and underscore the importance of examining diet-cancer associations in different population subgroups.

Mediterranean populations' lower breast cancer incidence has been attributed to a traditional Mediterranean diet, but few studies have quantified Mediterranean dietary pattern intake in relation to breast cancer. We examined the association of a Mediterranean diet scale (MDS) with mammographic breast density as a surrogate marker for breast cancer risk. Participants completed a dietary questionnaire and provided screening mammograms for breast density assessment using a computer-assisted method. Among 1,286 women, MDS was not clearly associated with percent density in multivariate linear regression analyses. Because of previous work suggesting dietary effects limited to smokers, we conducted stratified analyses and found MDS and percent density to be significantly, inversely associated among current smokers (beta = -1.68, P = 0.002) but not among nonsmokers (beta = -0.08, P = 0.72; P for interaction = 0.008). Our results confirm a previous suggestion that selected dietary patterns may be protective primarily in the presence of procarcinogenic compounds such as those found in tobacco smoke.

Mediterranean populations' lower breast cancer incidence has been attributed to a traditional Mediterranean diet, but few studies have quantified Mediterranean dietary pattern intake in relation to breast cancer. We examined the association of a Mediterranean diet scale (MDS) with mammographic breast density as a surrogate marker for breast cancer risk. Participants completed a dietary questionnaire and provided screening mammograms for breast density assessment using a computer-assisted method. Among 1,286 women, MDS was not clearly associated with percent density in multivariate linear regression analyses. Because of previous work suggesting dietary effects limited to smokers, we conducted stratified analyses and found MDS and percent density to be significantly, inversely associated among current smokers (beta = -1.68, P = 0.002) but not among nonsmokers (beta = -0.08, P = 0.72; P for interaction = 0.008). Our results confirm a previous suggestion that selected dietary patterns may be protective primarily in the presence of procarcinogenic compounds such as those found in tobacco smoke.

Data regarding convenient, valid methods for measuring U.S. isoflavone intake are limited. We evaluated a soy food questionnaire (SFQ), the Willett food frequency questionnaire (FFQ), and overnight urine samples relative to excretion in 24-h urine samples. We also described intake among women in a high-risk program for breast or ovarian cancer. Between April 2002 and June 2003, 451 women aged 30 to 50 yr with a family history of breast or ovarian cancer completed the SFQ and FFQ. Of them, 27 provided four 24-h and overnight urine specimens. In these women, 24-h sample measures were correlated with SFQ estimates of daidzein (Spearman r = .48) and genistein (r = .54) intake, moderately correlated with the Willett FFQ (daidzein r = .38, genistein r = .33), and strongly correlated with overnight urine excretion (daidzein r = .84, genistein r = 0.93). Among all 451 SFQ respondents, mean (median) daidzein and genistein intakes were 2.8 (0.24) and 3.9 (0.30) mg/day. Primary sources of both were soymilk, soy nuts, and tofu. We conclude that targeted soy food questionnaires, comprehensive FFQs, and multiple overnight urines are all reasonable options for assessing isoflavone intake in epidemiologic studies.

The association of breast cancer with dietary patterns such as a western diet has not been studied in Asian women. We examined this among Shanghai Breast Cancer Study participants. Cases were of ages 25 to 64 years, diagnosed 08/1996-03/ 1998, and identified through a rapid case ascertainment system supplemented by the Shanghai Cancer Registry. Controls, selected from the general population of urban Shanghai, were frequency matched to cases by 5-year age group. Participants provided information on diet, lifestyle, and reproductive factors. In principal component analysis among 1,556 controls, two patterns emerged: a "vegetable-soy" pattern (tofu, cauliflower, beans, bean sprouts, green leafy vegetables) and a "meat-sweet" pattern (shrimp, chicken, beef, pork, candy, desserts). In adjusted unconditional logistic regression analyses including 1,446 cases and 1,549 controls with complete covariate data, risk was not associated with the vegetable-soy pattern. It was associated with the meat-sweet pattern (4th versus 1st quartile: odds ratio, 1.3; 95% confidence interval, 1.0-1.7; P-trend = 0.03), but only in postmenopausal women, specifically among those with estrogen receptor-positive tumors (4th versus Ist quartile: odds ratio, 1.9; 95% confidence interval, 1.1-3.3; P-trend = 0.03). Our findings indicate that a western diet increases breast cancer risk in postmenopausal Chinese women. They also suggest the value of quantifying aggregate risk for common combinations of foods.

BACKGROUND: Women with a family history of breast cancer may be at higher risk for breast cancer, but few previous studies evaluating diet and breast cancer have focused on such women. The objective of the present study was to determine whether diet, a modifiable risk factor, is related to breast density among women at high genetic risk for breast cancer. METHODS: Women with at least one first-degree or second-degree relative with breast cancer or ovarian cancer participating in the Fox Chase Cancer Center Family Risk Assessment Program completed health history and food frequency questionnaires and received standard screening mammograms. Cranial-caudal mammographic images were classified into the four Breast Imaging Reporting and Data System categories ranging from 'entirely fatty' to 'extremely dense'. Logistic regression analysis using proportional odds models for polychotomous outcomes provided estimates of odds ratios for having a higher category versus a lower category of breast density. RESULTS: Among 157 high-risk women, breast density was inversely associated with vitamin D intake (odds ratio for third tertile versus first tertile, 0.5; 95% confidence interval, 0.2-1.0). In contrast, intakes above the median level for protein (odds ratio, 3.0; 95% confidence interval, 1.3-6.9) and above the median level for animal protein (odds ratio, 4.3; 95% confidence interval, 1.8-10.3) were associated with higher breast density, but only among women whose family history did not reflect a known familial cancer syndrome or a breast cancer predisposition gene. CONCLUSION: For women with a strong family history that was not associated with known cancer syndromes, dietary factors may be associated with breast density, a strong predictor of breast cancer risk. Since women with strong family history are often very motivated to change their lifestyle habits, further studies are needed to confirm whether changes in diet will change the breast density and the subsequent onset of breast cancer in these women.

Objectives The objectives of the present study were to examine sociodemographic correlates of soy food consumption among women at increased risk of breast cancer, describe factors influencing soy food consumption or nonconsumption, and identify women's sources of information about soy foods. Design A cross-sectional, self-report survey was used to assess frequency of and factors influencing soy food consumption. Soy food intake was reported for the past year. Subjects/setting Participants were 452 women, with family histories of breast cancer who were enrolled in a cancer risk assessment program. Statistical analyses performed Comparisons between consumers and nonconsumers of soy foods were performed using multivariate logistic regression and chi(2) analyses. Results Thirty-two percent reported soy food consumption. Commonly consumed soy foods were vegetable burgers, tofu, and soymilk. Consumers of soy foods were more likely to have higher levels of education and report eating five or more daily servings of fruits and vegetables. The primary reason for consumption of soy foods was eating a healthful diet, whereas insufficient knowledge about soy food preparation was the primary reason stated for nonconsumption. Both consumers and nonconsumers reported obtaining information about soy foods from magazines, friends, and newspapers. Consumers also indicated using the Internet to seek information. Conclusions These findings contribute to our understanding of the level of soy intake among women at increased risk for breast cancer and highlight potential factors that may influence women's decisions regarding soy food consumption. Women, particularly in this vulnerable population, would benefit from clear messages regarding the health effects of soy.

The formation of the primitive endoderm covering the inner cell mass of early mouse embryos can be simulated in vitro by the differentiation of mouse embryonic stem (ES) cells in culture following either aggregation of suspended cells or stimulation of cell monolayers with retinoic acid. The developmentally regulated transcription factors GATA-4 and GATA-6 have determining role in mouse extraembryonic endoderm development. We analyzed the in vitro differentiation of mouse embryonic stem cells deficient of GATA factors and conclude that GATA-4 is required for ES cells to perceive a cell positioning (cell aggregation) signal and GATA-6 is required to sense morphogenic (retinoic acid) signal. The collaboration between GATA-6 and GATA-4, or GATA-6 and GATA-5 which can substitute for GATA-4, is involved in the perception of differentiation cues by embryonic stem cells in their determination of endoderm lineage. This study indicates that the lineage differentiation of ES cells can be manipulated by the expression of GATA factors. Hepatitis C virus (HCV) is a positive strand RNA virus with a narrow host and tissue tropism. It ranks among the most significant of human pathogens, causing inflammation, scarring and cancer of the liver. Recent investigations have shed light on some of the salient molecular features of this virus. These include a requirement for CD81 (a tetraspanin transmembrane protein for viral entry), a novel mechanism for the initiation of RNA synthesis, phosphorylation of a viral protein in the regulation of RNA amplification and virus assembly and, finally, a viral protease suppressing activation of the innate immune response in infected cells. The most significant recent advances in the application of monoclonal antibodies (mAbs) to oncology have been the introduction and approval of bevacizumab (Avastin), an anti-vascular endothelial growth factor antibody, and of cetuximab (Erbitux), an anti-epidermal growth factor antibody. In combination with standard chemotherapy regimens, bevacizumab significantly prolongs the survival of patients with metastatic cancers of the colorectum, breast and lung. Cetuximab, used alone or with salvage chemotherapy, produces clinically meaningful anti-tumor responses in patients with chemotherapy-refractory cancers of the colon and rectum. In addition, the anti-HER2/neu antibody trastuzumab (Herceptin), in combination with standard adjuvant chemotherapy, has been shown to reduce relapses and prolong disease-free and overall survival in high-risk patients after definitive local therapy for breast cancer. These exciting recent results provide optimism for the development of mAbs that bind novel targets, exploit novel mechanisms of action or possess improved tumor targeting. Progress in the clinical use of radioimmunoconjugates remains hindered by complexity of administration, toxicity concerns and insufficiently selective tumor targeting. Endoscopy plays a critical role in the management of patients with malignancies involving the gastrointestinal tract. Endoscopic ultrasound has provided essential staging information, made more complete by the ability to perform fine needle aspiration of suspicious lymph nodes. Novel endoscopic resection and ablative techniques are expanding therapeutic choices in premalignant and malignant conditions. Obstruction, virtually anywhere along the length of the gastrointestinal tract, can be relieved with new stents. All of these advances have made the therapeutic gastroenterologist a key member of the team managing patients with tumors of the gastrointestinal tract. The objective of this cross-sectional study was to compare dietary reports from a food frequency questionnaire (FFQ) for US Chinese women with 24-hour recall estimates. The subjects were 56 women recruited through organizations in Philadelphia's Chinese community. Spearman correlations were used to describe FFQ estimates of food servings per month and nutrient intake per day vs estimates from three 24-hour recalls over 1 month. On average, women reported at least weekly consumption of 28 of 96 FFQ food items. The three most frequently consumed were rice (38 times/month), tea (29 times/month), and dark green, leafy vegetables (18 times/month). Comparing reported frequencies of the 28 foods to 24-hour recall estimates, the median Spearman correlation was 0.36. For nutrient estimates, correlations were high (r >0.5) for dietary fiber and calcium; moderate ( r =0.25 to 0.5) for energy, saturated fat, cholesterol, carbohydrates, protein, folic acid, and iron; but poor (r <0.25) for total fat, vitamin C, vitamin A, and carotene. These findings provide some assurance of the FFQ's adequacy for describing US Chinese women's intake of commonly consumed foods and selected nutrients. They also provide a basis for further improvements to, and evaluations of, the FFQ.