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ACCOMPLISHMENTS

Aim 1:  Decrease the incidence and slow the progression of cancer

Epidemiologic Studies

a)      Genetic and Molecular Epidemiology

            Dr. Jianfeng Xu and colleagues (Drs. Bao-Li Chang and Siqun Zheng) have identified two prostate susceptibility genes (MSR1 and RNASEL), described in Nature Genetics (Carpten et al., 2002; Xu, et al., 2002) and several prostate cancer risk modifier genes (TLR genes), providing strong support for a novel inflammation hypothesis of prostate cancer.  This group of molecular and genetic epidemiologists was formed in 2000 and under Dr. Xu’s leadership has evolved from a two member team that was focused solely on genetic linkage analysis of prostate cancer to an internationally recognized comprehensive research team performing foundational molecular epidemiologic work in prostate cancer including germline and somatic genetic changes, as well as epigenetic changes. They have contributed significantly to the field of prostate cancer genetics by identifying multiple chromosomal regions that likely harbor major prostate cancer susceptibility genes. The findings have been published in the Proceedings of the National Academy of Sciences (Gillanders et al, 2004) and American Journal of Human Genetics (Xu and ICPCG, 2005). These linkage regions will receive intensive attention in the NCI CGEM study that will identify prostate cancer genes using a genome-wide association approach.   Since 2000, this group of cancer control investigators has published over 55 peer-reviewed cancer related papers, including two papers in Nature Genetics, four papers in JNCI, one paper in PNAS, ten papers in Cancer Research, and five papers in American Journal of Human Genetics. 

Another achievement is the identification of a critical mutation in a prostate specific gene NKX3.1. The mutation completely co-segregates with prostate cancer in a prostate cancer family. They also found functional impact of the mutation. (Zheng et al., Cancer Research, 2005).  Together with investigators at the Karolinska Institute in Sweden and Johns Hopkins Medical Center they have obtained multiple pieces of genetic evidence to support a role of inflammation in prostate cancer development. Their findings of a genetic association between prostate cancer risk and several key genes regulating the inflammatory process are the basis for a new inflammation hypothesis of prostate cancer. Their results were recently published in two JNCI papers (Lindmark et al., 2004; Sun et al., 2005), Cancer Research (Zheng, 2004), and several other high impact  journals (Sun et al.,Cancer Epidemiol Biomarkers Prev 2004; Lindmark et al., Br J Cancer, 2005; Lindstrom et al., Hum Genet, 2005; Xu et al., Cancer Epidemiol Biomarkers Prev, 2005; Sun et al., Prostate, 2005).

An emerging area in the field of genetics and cancer disparities is work conducted by Drs. Xu and Chang to study racial differences due to genetics in prostate cancer.  Racial Differences in Prostate Cancer: Influences of Health Care Interaction and Host and Tumor Biology (DOD; Co-PI Jianfeng Xu) evaluates whether the different risks and severity of prostate cancer among whites and blacks is due to differences in mutations and frequencies of MSR1.  Dr. Chang has just received funding for another study to examine the genetic epidemiology of prostate cancer in African-American and Caucasian men (DOD; “Contribution of AMACR and Phytanic Acid to Prostate Cancer Risk among African-American Men in North Carolina”, PI: Bao-Li Chang, Co-Is: Mara Vitolins, Jianfeng Xu). This study will recruit prostate cancer case-control study subjects in North Carolina to identify prostate cancer genetic and dietary susceptibility factors.  

b)      Nutrition and Environmental Risks

The vitamin D work of Dr. Gary G. Schwartz and colleagues provides an example of our translational work.  Much of the interest in vitamin D stems from observations made by Dr. Schwartz and colleagues that prostate cancer mortality rates are highest where sunlight is most scarce.  They suggested that this was due to the influence of vitamin D, which is derived from sunlight, in maintaining the normal phenotype of prostate cells. This hypothesis led to both chemoprevention trials and chemotherapeutic trials at WFUSM. This area began as a classic example of translational research from the “trench” to the bench in which Dr. Schwartz’s epidemiological work stimulated basic research on vitamin D and prostate biology by Dr. Cramer and other members of the CGS Program. Their collaboration led to additional translational bench-to-bedside research, such as the Zemplar trial in the Clinical Program; to collaboration with members of the DNAD Program on vitamin D and radiosensitization; and to collaboration within the CGS Program on the synergism between vitamin D and soy isoflavones. 

Human prostate cells are known to possess specific receptors for the hormonal form of vitamin D, 1, 25(OH)2D.  Dr. Schwartz and colleagues have shown have shown that when human prostate cancer cells are exposed to 1, 25(OH)2D, 1, 25(OH)2D promotes their differentiation and inhibits their proliferation, invasiveness, and metastases. These findings have led to human clinical trials of vitamin D and its 1, 25(OH)2D and 1, 25(OH)2D analogues as therapy for prostate cancer. They have recently demonstrated that prostate cells synthesize 1, 25(OH)2D from its prohormonal precursor, 25-Hydroxyvitamin D - an ability previously believed to be exclusive to kidney cells and keratinocytes.

Drs. Mark Cline (of the Cell Growth and Survival Program) and Mara Vitolins are collaborating to determine whether dietary soy in men with prostate cancer has an effect on the proliferation in neoplastic and adjacent prostate tissues.  This work began within the Cancer Center and led to an R03 grant (“Effects of Dietary Soy on Biomarkers in Prostate”).  Previous collaborations on soy protein research began with animal models, and the resulting data were used to support the conduct of a human clinical trial, the Soy Estrogen Alternative (SEA) study, which evaluated biomarkers in peri- and postmenopausal women.  This collaboration has led to funding of a variety of animal and human trials of soy intervention including evaluating biomarkers of prostate cancer (“Effects of Dietary Soy on Biomarkers in Prostate Cancer”, “Use of a Soy-based Meal Replacement Weight Loss Intervention for Survivors of ER/PR Negative Breast Cancer”, and the “Soy Trial of the Prostate” (CALGB-NCI)). 

Our work with Hispanic farmworkers provides an example of research that has progressed from discovery to translation to dissemination and builds on our work with the rural Hispanic community. Dr. Tom Arcury continues his focus on Hispanic farmworkers to examine pesticide exposure and green tobacco sickness.  He found that farmworkers were exposed to carcinogenic pesticides and used cigarette smoking to reduce the incidence of green tobacco sickness (acute nicotine poisoning following dermal contact with mature tobacco plants).  These findings were used to develop successful grant proposals testing intervention programs related to farm worker safety to reduce exposure to carcinogenic pesticides.  “Preventing Agricultural Chemical Exposure (PACE)” was a community-based study to develop and test culturally appropriate interventions to reduce chemical exposure in seasonal and migrant farmworkers.  Baseline data showed that only one third of farmworkers in North Carolina ever receive pesticide safety training, which is mandated for all workers at risk of exposure by the EPA’s Worker Protection Standard. Data from “Green Tobacco Sickness among Minority Farmworkers” also showed that green tobacco sickness is a major health problem for seasonal and migrant farmworkers.  Results from these studies were used to develop another study of farmworker health disparities, “Occupational Skin Disease among Minority Farmworkers”.  Dr. Arcury continues to study the epidemiology of this illness and is expected to receive funding to continue this work (“Community Participatory Approach to Measuring Farmworker Pesticide Exposure: PACE3”).  The dissemination plan of this research addresses procedures for returning results to individual participants, and communicating results to farmworkers, service providers, and policy makers.

Behavioral and Pharmacologic Interventions

Drs. John Spangler, Kristie Long Foley, and Sonia Crandall created a tobacco cessation program for medical students using standardized patient instructors and a formal evaluation methodology. This program, designed to train physicians to successfully counsel patients in quitting, has won two national awards and was recently selected as an innovation in medical education by Academic Medicine. In 2003, Drs. Spangler, Foley, and Crandall received an NCI R25E training grant to develop a “Culturally Competent Web-Based Tobacco Curriculum” that builds upon these efforts. This program is culturally relevant, portable, and will be disseminated to medical schools nationwide.

Cancer and cognition is an emerging area in our Program in which ongoing studies conducted by Drs. Sally Shumaker (Cancer Control) and Stephen Rapp (Clinical Program) provide unique opportunities.  One example is “Cognition in the Study of Tamoxifen and Raloxifene (Co-STAR)”, an ancillary study to the “Study of Tamoxifen and Raloxifene (STAR) for the Prevention of Breast Cancer”. STAR is a randomized trial designed to ascertain the relative prevention benefits and side effects of these two drugs in healthy women. Co-STAR is designed to determine the effects of tamoxifen and raloxifene on cognitive aging in non-demented STAR participants. The methods employed in Co-STAR parallel those used in the “Effects of Hormone Replacement Therapy on Cognitive Aging: Women’s Health Initiative Study on Cognitive Aging (WHISCA)”. WHISCA, an ancillary study to WHI, was designed to assess normal cognitive aging among a subset of postmenopausal women randomized to hormone therapy in the WHI hormone therapy trials.

Early Detection

Researchers at WFUSM have a long history of promoting early detection among underserved populations. The reputation of the CCCWFU has enabled the Cancer Control Program to create lasting partnerships with community-based agencies (e.g., American Cancer Society) and stakeholders that have created entrée into predominantly poor, minority communities.  These partnerships, initially began as local county-based projects but evolved into a T32 partnership grant across two-states. These grants have crossed disease sites (cervical, breast, colon), ethnicity, and geography.

The “Robeson County Outreach, Screening and Education (ROSE)” project increased mammography utilization among high-risk African American, Native American and White women in eastern NC. Using interventions that targeted women through lay health advisors and local health care providers, investigators in the program demonstrated that screening rates could be improved among poor, high-risk women by increasing access and reducing barriers to early detection.  Building upon the success of ROSE, funding was received for the “Carolina Colorectal Cancer Screening study (CARES)” to improve colorectal cancer screening among African-American, low-income women in North and South Carolina (PIs: Paskett/ Kristie Foley). This project was a quasi-experimental, community-based trial to increase endoscopy among low-income women living in subsidized housing.  Using a T32 partnership grant sponsored by the American Cancer Society, we developed a sustainable program of colorectal screening education deliverable through local cancer control managers.

Dr. Kristie Foley recently completed a pilot study of Pap smear screening among Latina women (“CAPRELA: Cancer Prevention among Latinas”), which found poor regular utilization of free Pap smear screening (33%) among uninsured Latina women; this pilot study led to community-based intervention to improve Pap smear rates in this population. Drs. Foley and Brigitte Miller (Ob/Gyn-Clinical Program) have collaborated to test the effect of two different interventions to increase colposcopic evaluation among women referred to the CCCWFU colposcopy clinic. These interventions tripled the colposcopy show rate (from 21% to 65%) among Latina women.

Most of our prior early detection work has focused on women. Dr. Tom Arcury has recently expanded these efforts to men.  Partnering with Clinical Program colleagues (Drs. Peter Clark and John Stewart IV) he has received R01 funding for “African American Men Prostate and Colorectal Cancer Beliefs”.  This project will determine if differences between African American and white men in their knowledge, beliefs and behavior of about prostate and colorectal cancer and screening are related to differences in social class, health care access, or culture.  Interventions to increase screening among African American men will ultimately be tested.  Another promising new direction for early detection is “Overcoming Literacy Barriers in Colorectal Cancer”, an ACS Career Development grant awarded to Dr. David Miller (Internal Medicine).  This project, which originated from a Pull grant received from CCCWFU, focuses on using an interactive web-based multimedia educational computer program to address barriers faced by people with low literacy skills.

Aim 2:  Survivorship: Improve Quality of Life and Survival of Those Who Develop Cancer

Epidemiologic Studies of Cancer Survivors

Our epidemiologic studies of quality of life in cancer survivors are providing data that will lead to improved targeted interventions in survivorship.  These studies focus on collecting detailed information on the impact of chemotherapy on menstrual cycle changes and fertility, age differences in response to breast cancer, QOL at different stages of the disease process for ovarian cancer patients, and QOL of long-term cancer survivors.   The DOD funded Behavioral Center of Excellence in Breast Cancer (Functional Status and Quality of Life Across the Lifespan, PI: Michelle Naughton) explores quality of life issues for breast cancer survivors across the lifespan.  The DOD Center contains three separate, but interrelated research projects.

Project #1, “Menstrual Cycle Maintenance and Quality of Life Following Treatment for Breast Cancer: A Prospective Study” (PI: Dr. Michelle Naughton), is a continuation and expansion of a previous DOD grant begun in 1996 to study menstrual cycle patterns following treatment for breast cancer. To our knowledge, this is the largest prospective study in the world to determine the impact of breast cancer treatment on menstrual bleeding/amenorrhea and subsequent fertility, as well as a wide variety of QOL issues in a total of 850 women survivors of breast cancer. Analyses to date are yielding significant findings on how menstrual cycle patterns following chemotherapy differ according to specific type of chemotherapy and the patient’s age.

The second project (Project #2, “Investigating Mechanisms to Explain Age Associated Differences in Quality of Life among Breast Cancer Patients”; PI: Dr. Nancy Avis) is designed to better understand why younger women have greater psychological morbidity following a breast cancer diagnosis than older women. Considerable research has shown that younger women have a more difficult time adjusting to a breast cancer diagnosis.  Although several hypotheses have been generated – e.g., younger women have more aggressive treatment, they have more family and work responsibilities, it is an off-time event - no study has tested these various hypotheses.   Understanding reasons for these age differences in adjustment will lead to improved interventions to help younger women adjust to a breast cancer diagnosis and treatment.  This prospective observational cohort study looks at treatment characteristics, personal resources (e.g., social support, coping strategies, resiliency), and the impact of cancer on life roles and responsibilities on QOL.

Project #3, “Research on Optimal Recovery Practices in Breast Cancer (RESTORE)” (PI: Dr. Roger Anderson; Co-I: Dr. Shannon Mihalko) is testing two exercise interventions in 100 women, aged 40 years old and older, recently diagnosed with breast cancer to improve QOL and reduce lymphedema. Results of the main study are not yet available; however, analyses of the lymphedema portion have shown that combining fitness exercises, arm movement, a compression sleeve, and lymphedema education can effectively prevent lymphedema 6 to 9 months post-surgery among patients with node-positive disease. This important and understudied area has the opportunity to improve the QOL of many breast cancer survivors by improving postoperative patient care. 

The Quality of Life in Adult Cancer Survivors project (P.I. Nancy Avis) brings together our expertise in QOL measurement and interest in long-term survivorship.  As researchers and clinicians become more interested in long-term cancer survivors, it is critical to have a QOL instrument relevant to survivorship issues.  While numerous quality of life measures already exist, these measures tend to focus on issues for patients who are newly diagnosed with cancer or in treatment.  In the first part of this project we developed a QOL instrument specifically for long-term cancer survivors, using both qualitative and quantitative research to identify particular issues faced by long-term cancer survivors (Avis et al., 2005; Foley et al, 2006).  The Quality of Life in Adult Cancer Survivors Scale (QLACS) has been shown to have good psychometric properties in terms of validity and reliability.  In the second phase of this project we recontacted the women from the cross-sectional phase of the Breast Cancer in Younger Women Study to examine additional psychometric properties of the QLACS.  This research has shown that the QLACS has good retrospective validity and is generally responsive to change.  The QLACS has already generated interest among long-term survivor researchers and is being used in our DOD studies and by investigators.

Dr. Nancy Avis’ “A Treatment Stage Specific Approach to Improving Quality of Life for Women with Ovarian Cancer”, seeks to determine QOL issues at four different stages: at diagnosis, in treatment, post treatment, and at recurrence, To date, most QOL interventions focus on the time period immediately after a cancer diagnosis.  However, the hypothesis of this study is that the issues patients deal with and that impact their QOL change according to stage of treatment.  If this hypothesis holds true, it will have important implications for the timing of the delivery of interventions to improve QOL.

The “Breast Cancer in Younger Women: Improving Quality of Life”, PI: Dr. Nancy Avis, project was conducted in two phases. The first phase was a cross-sectional observational study of women who had been diagnosed with breast cancer within the past three years. Results showed that the major problems reported by women were symptoms related to menopause, concerns about appearance, and sexual functioning. The second phase of this project was an intervention study in which newly diagnosed women were randomly assigned to receive a videotape developed specifically for this study or a standard booklet, and followed up to a year post surgery. Results indicated that QOL was primarily related to psychosocial factors such as coping and social support, not medical factors. (Avis, Crawford, Manuel, Psycho-Oncology, 2004; Avis, Crawford, Manuel, J Clin Oncol, 2005; Burwell, Case, Kaelin, Avis, J Clin Oncol, 2006)

Improving Quality of Life through Symptom Management and Behavioral Interventions

A developing area of survivorship is the use of complementary/integrative therapies for symptom management, which have the potential to significantly improve QOL among cancer survivors.   Hot flashes are particularly problematic, because the most effective treatment, hormone therapy (HT), is contraindicated for survivors of hormone-dependent cancers.  Dr. Nancy Avis’ NCI funded study “Acupuncture Treatment for Menopausal Hot Flashes” grows out her research on menopause and the “Breast Cancer in Younger Women” study, which found that menopause resulting from chemotherapy was one of the biggest problems women faced.  This is study is randomly assigning perimenopausal women with significant hot flashes to one of three groups:  1) standard acupuncture with variation, 2) sham acupunction, or 3) usual care.

Dr. Michelle Naughton is beginning a Phase II Research Base study of St John’s Wort for treatment of hot flashes for women with a history of breast cancer to determine 1) the efficacy of St. John’s Wort in reducing hot flushes in breast cancer survivors at least 2 years post-treatment, and 2) the effect of St. John’s Wort on tamoxifen levels, in those women taking the medication. 

The above studies focus on hot flashes in women, but disabling hot flashes are also experienced by two thirds of men who undergo hormone manipulation for prostate cancer.   These symptoms may continue for months after adjuvant therapy is completed and years during chronic therapy and have been shown to adversely affect QOL.  Dr. Mara Vitolins has recently received extramural funding under the CCOP Research Base to examine, in a placebo-controlled trial, the role of soy and Effexor for treating vasomotor symptoms in men with prostate cancer. This study, “Randomized Study of Soy Protein and Effexor on Vasomotor Symptoms of Men with Prostate Cancer”, will randomly assign 166 men receiving hormonal manipulation treatment for prostate cancer to receive: 1) soy protein powder, 2) Effexor, 3) a combination of soy and Effexor, or 4) a placebo.  This research grows out of earlier work conduced by Drs. Mara Vitolins and Greg Burke exploring the role of soy for the relief of vasomotor symptoms among menopausal women and the work being done by Dr. Mark Cline using animal models of prostate cancer.

Patterns of Care

Our Program is developing the area of research that focuses on patterns of care to examine non-medical factors that influence the care cancer patients receive and whether patients are receiving recommended treatments.  We have chosen to focus on methodological issues of automated data to define patterns of care, cancer care received by low income populations, and treatment effectiveness.  One such methodological issue is the absence of good radiation and chemotherapy treatment data in the State Tumor Registry.  Drs. Anderson, Foley and colleagues from the CCCWFU Clinical Program have developed methodological techniques to merge Medicaid and tumor registry data to provide a much more complete record of initial cancer treatments.   This serves as the basis of a study that will evaluate patterns of outcomes in our region.

In their ACS-funded study “Classification of Care for Breast Cancer under Medicaid”, Drs. Roger Anderson and Kristie Foley documented multiple possible treatment disparities. Black women were more likely to have breast conserving surgery than white women, but less likely to receive radiation therapy. Women with more co-morbidities were more likely to receive mastectomy and chemotherapy. These findings have led to a competitive renewal, “Outcomes of Omission of Radiation with Lumpectomy among Low-Income Women”. Drs. Anderson, Foley, and Gretchen Kimmick (from Duke University Medical School) seek to ascertain the extent to which omission of radiation is causally linked to poorer survival. They also propose to add hormonal therapy to the dataset using existing Medicaid prescription claims which will provide additional data on access to care and is an important predictor for recurrence and survival analyses.

The “Breast and Prostate Cancer Data Quality and Patterns of Care” (CDC) study, Dr. Roger Anderson, will test the efficiency and effectiveness of a targeted audit protocol for registry data to improve the overall quality of registry data; assess the quality, completeness of staging and first course of treatment collected by the NC Central Cancer Registry using electronic edits and case record re-abstraction; and describe the receipt of standard of care for breast and prostate cancer.

Dr. Ann Geiger‘s “Breast Cancer Treatment Effectiveness in Older Women” is a medical-record-based, retrospective cohort study evaluating the effectiveness of primary and adjuvant therapies in preventing recurrence and death in women diagnosed with breast cancer at age 65 years and older, a group understudied in the clinical trials setting and in which therapy options are complicated by the presence of co-morbidities.  This study is based in the NCI-funded HMO Cancer Research Network, in which automated data on large and diverse populations provide a unique opportunity for treatment effectiveness studies.   

In “Is Stroke a Late Effect of Chemotherapy?”, Dr. Ann Geiger anticipates using automated data to estimate the association of stroke with chemotherapy among a group of over 110,000 ethnically diverse patients diagnosed with various types of cancer.

Selected Publications:

Anderson GL, Limacher M, Bonds D, Shumaker S, Prineas R, Naughton M, Burke G, Crouse R, Vitolins M, Washburn S.  2004.  Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial, JAMA, 291(14),1701-1712

Arcury TA, Bell RA, Vitolins MZ,Quandt SA.  2005.  Rural older adults' beliefs and behavior related to complementary and alternative medicine use, Complement Health Pract Rev,10 (1),33-44

Arcury TA, Quandt SA.  2003.  Pesticides at work and at home: exposure of migrant farmworkers, Lancet,362(9400),2021

Arcury TA, Quandt SA, Bell RA.  2001.  Staying healthy: the salience and meaning of health 2maintenance behaviors among rural older adults in North Carolina, Soc Sci Med,53(11),1541-1556

Arcury TA, Quandt SA, Preisser JS, Bernert JT, Norton D, Wang J.  2003.  High levels of transdermal nicotine exposure produce green tobacco sickness in Latino farmworkers, Nicotine Tob Res,5(3),315-321

Arcury TA, Quandt SA, Preisser JS, Norton D.  2001.  The incidence of green tobacco sickness among Latino farmworkers, J Occup Environ Med, 43 (7),601-609

Arcury TA, Quandt SA, Russell GB.  2002.  Pesticide safety among farmworkers: perceived risk and perceived control as factors reflecting environmental justice.  Environ Health Perspect 110(Suppl 2):233-240

Avis NE, Assmann SF, Kravitz HM, Ganz PA, Ory M.  2004.  Quality of life in diverse groups of midlife women: assessing the influence of menopause, health status and psychosocial and demographic factors, Qual Life Res,13 (5),933-946

Avis NE, Crawford S, Manuel J.  2004.  Psychosocial problems among younger women with breast cancer, Psychooncology,13 (5),295-308

Avis NE, Crawford S, Manuel J.  2005.  Quality of life among younger women with breast cancer, J Clin Oncol,23 (15),3322-3330

Avis NE, Ory M, Matthews KA, Schocken M, Bromberger J, Colvin A.  2003.  Health-related quality of life in a multiethnic sample of middle-aged women: Study of Women's Health Across the Nation (SWAN), Med Care,41 (11),1262-1276

Avis NE, Smith KW, Link CL, Goldman MB.  2004.  Increasing mammography screening among women over age 50 with a videotape intervention, Prev Med,39(3),498-506

Avis NE, Smith KW, Link CL, Hortobagyi GN, Rivera E.  Factors associated with participating in breast cancer treatment clinical trials.  Journal of Clinical Oncology 2006, 24

Avis NE, Smith KW, McGraw S, Smith RG, Petronis VM, Carver CS.  2005.  Assessing quality of life in adult cancer survivors (QLACS), Qual Life Res,14 (4),1007-1023

Avis NE, Zhao X, Johannes CB, Ory M, Brockwell S, Greendale GA.  2005Correlates of sexual function among multi-ethnic middle-aged women: results from the Study of Women's Health Across the Nation (SWAN), Menopause,12 (4),385-398

Baffoe-Bonnie AB, Smith JB, Stephan DA, Schleutker J, Carpten JD, Kainu T, Gillanders EM, Matikainen M, Xu JF, et al.  2005.  A major locus for hereditary prostate cancer in Finland: localization by linkage disequilibrium of a haplotype in the HPCX region.  Human Genetics 117(4):307-316

Bell RA, Shelton BJ, Paskett ED 2001.  Colorectal cancer screening in North Carolina: associations with diabetes mellitus and demographic and health characteristics.  Prev Med 32(2):163-167

Brown WM, Lange EM, Chen H, Zheng SL, Chang B, Wiley KE, Isaacs SD, Xu J, Isaacs WB, Cooney KA.  2004.  Hereditary prostate cancer in African American families: linkage analysis using markers that map to five candidate susceptibility loci.  Br J Cancer 90(2):510-514

Burke GL, Legault C, Anthony M, Bland DR, Morgan TM, Naughton MJ, Leggett K, Washburn SA, Vitolins MZ. Soy protein and isoflavone effects on vasomotor symptoms in peri- and postmenopausal women: the Soy Estrogen Alternative Study. Menopause. 2003 Mar-Apr;10(2):147-53

Burwell SR, Case LD, Kaelin C, Avis NE.  Sexual problems in younger women following breast cancer surgery.  Journal of Clinical Oncology, in press.

Chang B-L, Gillanders EM, Isaacs SD, Wiley KE, Adams T, Turner AR, Zheng SL, Meyers DA, Carpten JD, Xu J.  2005.  Evidence for a general cancer susceptibility locus at 3p24 in families with hereditary prostate cancer.  Cancer Lett 219(2):177-182

Chang B-L, Isaacs SD, Wiley KE, Gillanders EM, Zheng SL, Meyers DA, Walsh PC, Trent JM, Xu J, Isaacs WB.  2005.  Genome-wide screen for prostate cancer susceptibility genes in men with clinically significant disease.  Prostate 64(4):356-361

Chang B-L, Zheng SL, Hawkins GA, Isaacs SD, Wiley KE, Turner A, Carpten JD, Bleecker ER, Meyers DA, Xu J.  2002.  Joint effect of HSD3B1 and HSD3B2 genes is associated with hereditary and sporadic prostate cancer susceptibility, Cancer Res,62 (6),1784-1789

Chang B-L, Zheng SL, Hawkins GA, Isaacs SD, Wiley KE, Turner A,Carpten JD, Bleecker ER, Meyers DA, Xu J.  2002.  Polymorphic GGC repeats in the androgen receptor gene are associated with hereditary and sporadic prostate cancer risk, Hum Genet,110(2),122-129

Chang B, Zheng SL, Isaacs SD, Turner A, Hawkins GA, Wiley KE, Bleecker ER, Walsh PC, Meyers DA, Xu J.  2003.  Polymorphisms in the CYP1A1 gene are associated with prostate cancer risk.  Int J Cancer 106(3):375-378

Chang BL, Zheng SL, Isaacs SD, Turner AR, Hawkins GA, Wiley KE, Bleecker ER, Walsh PC, Meyers DA, Xu J.  2003.  Polymorphisms in the CYP1B1 gene are associated with increased risk of prostate cancer.  Br J Cancer 89(8):1524-1529

Chang B, Zheng SL, Isaacs SD, Wiley KE, Carpten JD, Hawkins GA, Bleecker ER, Walsh PC, Meyers DA, Xu J.  2001.  Linkage and association of CYP17 gene in hereditary and sporadic prostate cancer.  Int J Cancer 95(6):354-359

Chang B, Zheng SL, Isaacs SD, Wiley KE, Turner A, Li G, Walsh PC, Meyers DA, Isaacs WB, Xu J.  2004.  A polymorphism in the CDKN1B gene is associated with increased risk of hereditary prostate cancer.  Cancer Res 64(6):1997-1999

Chen TC, Holick MF, Lokeshwar BL, Burnstein KL, Schwartz GG.  2003.  Evaluation of vitamin D analogs as therapeutic agents for prostate cancer, Recent Results Cancer Res,164, 273-288

Cramer SD(CGS), Chang B-L, Rao A, Hawkins GA, Zheng SL, Wade WN, Bleecker ER, Meyers DA, Ohar J, Xu J.  2003.  Association between genetic polymorphisms in the prostate-specific antigen gene promoter and serum prostate-specific antigen levels.  J Natl Cancer Inst 95(14):1044-1053

Foley KL, Crandall SJ, George G, Roman M, Spangler JG.  2003.  Reliability of a smoking cessation risk factor interview scale (SCRFIS) for use with standardized patient instructors, J Cancer Educ,18 (3),134-141

Foley KL, Farmer DF, Petronis VM, Smith RG, McGraw S, Smith K, Carver CS, Avis NE.  2005.  A qualitative exploration of the cancer experience among long-term survivors:  Comparison by cancer type, gender and age, Psychooncology. 2006 Mar;15(3):248-58

Foley KL, George G, Crandall SJ, Walker KH, Marion GS, Spangler JG. Training and evaluating tobacco-specific standardized patient instructors. Fam Med. 2006 Jan;38(1):28-37

Friedrichsen DM, Stanford JL, Isaacs SD, Janer M, Chang B, Deutsch K, Gillanders E, Kolb S, Zheng SL, Xu J.  2004.  Identification of a prostate cancer susceptibility locus on chromosome 7q11-21 in Jewish families.  Proc Natl Acad Sci U S A 101(7):1939-1944

Geiger AM, West CN, Nekhlyudov, L, Herrinton LJ, Liu IA, Altschuler A. Rolnick SJ, Harris EL, Greene SM, Elmore JG, Emmons KM, Fletcher SW. Contentment with quality of life among breast cancer survivors with and without contralateral prophylactic mastectomy. J Clin Oncol, 2006 Mar 20;24(9):1350-6

Gillanders EM, Xu J, Chang B, Lange EM, Wiklund F, Bailey-Wilson JE, Baffoe-Bonnie A, Zheng SL, Brown WM, Meyers DA.  2004.  Combined genome-wide scan for prostate cancer susceptibility genes.  J Natl Cancer Inst 96(16):1240-1247

Gold EB, Colvin A, Avis NE et al.    Longitudinal analysis of vasomotor symptoms and race/ethnicity across the menopausal transition:  Study of Women’s Health across the Nation (SWAN).  American Journal of Public Health, in press

Hawkins GA, Mychaleckyj JC, Zheng SL, Faith DA, Kelly B, Isaacs SD, Chang B-L, Xu J, Meyers DA, et al.  2002.  Germline sequence variants of the LZTS1 gene are associated with prostate cancer risk.  Cancer Genet Cytogenet 137(1):1-7.

Hays J, Ockene JK, Brunner RL, Kotchen JM, Manson JE, Patterson RE, Aragaki AK, Shumaker SA, Brzyski RG, LaCroix AZ.  2003Effects of estrogen plus progestin on health-related quality of life, N Engl J Med,348(19),1839-1854

Ho GY, Knapp M, Freije D, Nelson WG, Smith JR, Carpten JD, Bailey-Wilson JE, Xu J, Petersen G, Isaacs WB.  2002.  Transmission/disequilibrium tests of androgen receptor and glutathione S-transferase pi variants in prostate cancer families.  Int J Cancer 98(6):938-942

John EM, Dreon DM, Koo J,Schwartz GG.  2004.  Residential sunlight exposure is associated with a decreased risk of prostate cancer, J Steroid Biochem Mol Biol, 89-90,549-552

John EM, Schwartz GG, Koo J, Van Den Berg D, Ingles SA.  2005.  Sun exposure, vitamin D receptor gene polymorphisms, and risk of advanced prostate cancer, Cancer Res,65 (12),5470-5479

Killien M, Bigby JA, Champion V,Fernandez-Repollet E, Jackson RD, Kagawa-Singer M, Kidd K, Naughton MJ, Prout M.  2000.  Involving minority and underrepresented women in clinical trials: The National Centers of Excellence in Women's Health, Journal of Womens Health & Gender-Based Med,9(10),1061-1070

Koval AE, Riganti AA, Foley KL. CAPRELA (Cancer Prevention for Latinas): findings of a pilot study in Winston-Salem, Forsyth County.N C Med J. 2006 Jan-Feb;67(1):9-15

Lindmark F, Zheng SL, Wiklund F, Bensen J, Balter KA, Chang B,Hedelin M, Clark J, Meyers DA, Xu J.  2004.  H6D polymorphism in macrophage-inhibitory cytokine-1 gene associated with prostate cancer, J Natl Cancer Inst,96(16),1248-1254

Lippman SM, Goodman PJ, Klein EA, Parnes HL, Thompson IM Jr, Kristal AR, Santella RM, Schwartz GG, Moinpour CM, Coltman CA.  2005.  Designing the Selenium and Vitamin E Cancer Prevention Trial (SELECT).  J Natl Cancer Inst 97(2):94-102

Miller DC, Zheng SL, Dunn RL, Sarma AV, Montie JE, Lange EM, Meyers DA, Xu J, Cooney KA.  2003.  Germ-line mutations of the macrophage scavenger receptor 1 gene: association with prostate cancer risk in African-American men.  Cancer Res 63(13):3486-3489

Molnar I, Kute T, Willingham MC, Schwartz GG.  2004.  19-nor-1 alpha,25-dihydroxyvitamin D2 (paricalcitol) exerts anticancer activity against HL-60 cells in vitro at clinically achievable concentrations, J Steroid Biochem Mol Biol,89-90,539-543

Narla G, DiFeo A, Reeves HL, Schaid DJ, Hirshfeld J, Hod E, Xu J, Zheng SL, Chang B-L, Martignetti JA.  2005.  A germline DNA polymorphism enhances alternative splicing of the KLF6 tumor suppressor gene and is associated with increased prostate cancer risk.  Cancer Res 65(4):1213-1222

Naughton MJ, Jones AS, Shumaker SA.  2005.  When practices, promises, profits, and policies outpace hard evidence: the post-menopausal hormone debate, J Soc Issues,61(1),159-179

Naughton MJ, Petrek JA, Ip E, Paskett ED, Naftalis E.  2005.  Health-related quality of life of pre-menopausal breast cancer survivors, Journal of Clinical Oncology,23(16),37S-37S

Naughton MJ, Shumaker SA.  2003.  The case for domains of function in quality of life assessment, Qual Life Res,12(Suppl 1),73-80

Peppercorn J, Herndon J, Kornblith AB, Peters W, Ahles T, Vredenburgh J, Schwartz G, Shpall E, Hurd DD, Holland J, Winer E.  2005.  Quality of life among patients with Stage II and III breast carcinoma randomized to receive high-dose chemotherapy with autologous bone marrow support or intermediate-dose chemotherapy: Results form Cancer and Leukemia Group B 9066.  Cancer 104(8):1580-1589

Petrek JA, Naughton MJ, Case LD, Paskett ED, Naftalis EZ, Singletary SE, Sukumvanich P.  2005.  Incidence, time course, and determinants of menstrual bleeding after breast cancer treatment:  a prospective study.  Journal of Clinical Oncology 2006 Mar 1;24(7):1045-51. Epub 2006 Feb 13

Rapp SR , Rosdhal R, D'Agostino RB, Lovato J, Naughton M, Robbins ME, Shaw EG.  2004.  Improving cognitive functioning in brain irradiated patients: A phase II trial of an acetylcholinesterase inhibitor (donepezil).  Neuro-Oncology 6(4):357-357

Rapp SR, Espeland MA, Shumaker SA, Henderson VW, Brunner RL, Manson JE, Gass MLS, Stefanick ML, Coker LH, Dailey M.  2003.  Effect of estrogen plus progestin on global cognitive function in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial.  JAMA 289(20):2663-2672

Schwartz GG.  2005.  Vitamin D and the epidemiology of prostate cancer, Seminars In Dialysis,18(4),276-289

Shaw EG, Rosdhal R, D'Agostino RB, Lovato J, Naughton M, Rapp S.  2004.  A phase II study of donepezil in irradiated brain tumor patients: Effect on health-related quality of life and mood.  Neuro-Oncology 6(4):358-358

Shumaker SA, Legault C, Kuller L, Rapp SR, Thal L, Lane DS, Fillit H, Stefanick ML, Hendrix SL, Coker LH.  2004.  Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women's Health Initiative Memory Study, JAMA,291(24),2947-2958

Shumaker SA, Legault C, Rapp SR, Thal L, Wallace RB, Ockene JK, Hendrix SL, Jones BN III, Assaf AR, Jackson RD.  2003.  Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial, JAMA,289(20),2651-2662

Spangler JG, Case LD, Bell RA, Quandt SA.  2003.  Tobacco use in a tri-ethnic population of older women in southeastern North Carolina.  Ethn Dis 13(2):226-232

Spangler JG, Enarson C, Eldridge C.  2001.  An integrated approach to a tobacco-dependence curriculum, Acad Med,76(5),521-522

Spangler JG, George G, Foley KL, Crandall SJ.  2002.  Tobacco intervention training: current efforts and gaps in US medical schools.  JAMA 288(9):1102-1109

Spangler JG, Michielutte R, Bell RA, Dignan MB.  2001.  Association between smokeless tobacco use and breast cancer among Native-American women in North Carolina, Ethn Dis,11(1),36-43

Spangler JG, Michielutte R, Bell RA, Knick S, Dignan MB, Summerson JH.  2001.  Dual tobacco use among Native American adults in southeastern North Carolina, Prev Med,32(6),521-528

 Sun J, Zheng SL, Chang B, Li L, Li G, Liu W, Tolin A, Turner AR, Meyers DA, Xu J.  2005.  Sequence variants in Toll-like receptor gene cluster (TLR6-TLR1-TLR10) and prostate cancer risk, J Natl Cancer Inst,97(7),525-532

Sun J, Hedelin M, Zheng SL, Adami H-O, Bensen J, Chang B, Adams T, Turner A, Meyers DA, Xu J.  2004.  Interleukin-6 sequence variants are not associated with prostate cancer risk, Cancer Epidemiol Biomarkers Prev,13(10),1677-1679

      Vitolins MZ, Anthony M, Burke GL.  2001.  Soy protein isoflavones, lipids and arterial disease, Curr Opin Lipidol,12(4),433-437

Vitolins MZ.  2003.  Effects of soy protein in menopausal women: a review, Agro Food Industry Hi Tech,14(5),12-15

Walsh SR, Manuel JC, Avis NE.  2005.  The impact of breast cancer on younger women's relationships with their partner and children.  Families Systems Health 23(1):80-93

Whitlatch LW, Young MV, Schwartz GG, Flanagan JN, Burnstein KL, Lokeshwar BL, Rich ES, Holick MF, Chen TC.  2002.  25-hydroxyvitamin D-1 alpha-hydroxylase activity is diminished in human prostate cancer cells and is enhanced by gene transfer, J Steroid Biochem Mol Biol,81(2),135-14

Xu J, Gillanders EM, Isaacs SD, Chang B, Wiley KE, Zheng SL, Jones M, Gildea D, Riedesel E, Meyers DA.  2003.  Genome-wide scan for prostate cancer susceptibility genes in the Johns Hopkins hereditary prostate cancer families.  Prostate 57(4):320-325

Xu J, Langefeld CD, Zheng SL, Gillanders EM, Chang B, Isaacs SD, Williams AH, Wiley KE, Dimitrov L, Meyers DA.  2004.  Interaction effect of PTEN and CDKN1B chromosomal regions on prostate cancer linkage.  Hum Genet 115(3):255-262

Xu JF, Lowey J, Wiklund F, Sun JL, Lindmark F, Hsu FC, Dimitrov L, Chang BL, Turner AR, et al.  2005.  The interaction of four genes in the inflammation pathway significantly predicts prostate cancer risk.  Cancer Epidemiology Biomarkers & Prevention 14(11):2563-2568

Xu J, Meyers DA, Sterling DA, Zheng SL, Catalona WJ, Cramer SD (CGS), Bleecker ER, Ohar J.  2002.  Association studies of serum prostate-specific antigen levels and the genetic polymorphisms at the androgen receptor and prostate-specific antigen genes, Cancer Epidemiol Biomarkers Prev,11(7),664-669

Xu J, Thornburg T, Turner AR, Vitolins M, Case D, Sun J,Chang B, Adams TS, Zheng SL, Torti FM.  2005.  Serum levels of phytanic acid are associated with prostate cancer risk, Prostate,63(3),209-214

Xu J, Zheng SL, Carpten JD, Nupponen NN, Robbins CM, Mestre J,Moses TY, Faith DA, Bleecker ER, Meyers DA.  2001.  Evaluation of linkage and association of HPC2/ELAC2 in patients with familial or sporadic prostate cancer, Am J Hum Genet,68(4),901-911

Xu J, Zheng SL, Chang B,Smith JR, Carpten JD, Stine OC,Isaacs SD, Wiley KE, Bleeker [sic] ER [Bleecker, Meyers DA.  2001.  Linkage of prostate cancer susceptibility loci to chromosome 1, Hum Genet,108(4),335-345

Xu J, Zheng SL, Hawkins GA,Faith DA, Kelly B, Isaacs SD, Wiley KE, Chang B, Bleecker ER, Meyers DA.  2001.  Linkage and association studies of prostate cancer susceptibility: evidence for linkage at 8p22-23, Am J Hum Genet,69(2),341-350

Xu J, Zheng SL, Komiya A, Mychaleckyj JC, Isaacs SD, Chang B, Turner AR, Hawkins GA, Bleecker ER, Meyers DA.  2003.  Common sequence variants of the macrophage scavenger receptor 1 gene are associated with prostate cancer risk.  Am J Hum Genet 72(1):208-212

Xu J, Zheng SL, Mychaleckyj JC, Hu JJ, Lange EM, Hawkins GA, Turner A, Chang B, Hall MC, McCullough DL.  2002.  Germline mutations and sequence variants of the macrophage scavenger receptor 1 gene are associated with prostate cancer risk.  Nat Genet 32(2):321-325

Young MV, Schwartz GG, Wang L, Jamieson DP, Whitlatch LW, Flanagan JN, Lokeshwar BL, Holick MF, Chen TC.  2004.  The prostate 25-hydroxyvitamin D-1 alpha-hydroxylase is not influenced by parathyroid hormone and calcium: implications for prostate cancer chemoprevention by vitamin D.  Carcinogenesis 25(6):967-971

Zheng SL, Augustsson-Balter K, Chang B, Li L(CGS), Bensen J, Li G, Turner AR, Xu J, Meyers DA, Gronberg H.  2004.  Sequence variants of Toll-like receptor 4 are associated with prostate cancer risk: results from the Cancer Prostate in Sweden study.  Cancer Res 64(8):2918-2922

Zheng SL, Chang B-L, Faith DA, Johnson JR, Isaacs SD, Hawkins GA,Turner A, Bleecker ER, Meyers DA, Xu J.  2002.  Sequence variants of alpha-methylacyl-CoA racemase are associated with prostate cancer risk, Cancer Res,62(22),6485-6488

Zheng SL, Ju JH, Chang BL, Ortner E, Sun J, Isaacs SD, Sun J, Wiley KE, Liu W, Zemedkun M, Walsh PC, Ferretti J, Gruschus J, Isaacs WB, Gelmann EP, Xu J. Germ-line mutation of NKX3.1 cosegregates with hereditary prostate cancer and alters the homeodomain structure and function. Cancer Res. 2006 Jan 1;66(1):69-77

Zheng SL, Mychaleckyj JC, Hawkins GA, Turner A, Chang B, von Kap-Herr C, Pettenati M, Xu J, Meyers DA, et al.  2003.  Evaluation of DLC1 as a prostate cancer susceptibility gene: mutation screen and association study.  Mutat Res 528(1, 2):45-53

Zheng SL, Zheng W, Chang B, Shu X-O, Cai Q, Yu H, Dai Q, Xu J, Gao Y-T.  2003.  Joint effect of estrogen receptor beta sequence variants and endogenous estrogen exposure on breast cancer risk in Chinese women.  Cancer Res 63(22):7624-7629.

 

 

 

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