AMC Cancer Prevention & Control Program Scientific Achievements, 2008-2009
Scientific Progress and Achievement: This program’s past year’s scientific achievements can be seen in the publication and grant record. In the past 12 months, members of the AMC Cancer Prevention and Control Program have published 142 cancer-related manuscripts and have maintained an active portfolio of grants and contracts with a focus on cancer prevention and control.
Peer-reviewed Publications: Of the 142 cancer-related publications from members of this program in the past year, 37% (n = 52) were either inter- or intra-programmatic or both. This highlights the success of the UCCC in promoting collaborations among members of the Prevention & Control program and between Prevention and Control members and members of other programs.
Twelve of these publications are summarized below, with program members identified in bold. These 12 papers illustrate the breadth of cancer prevention and control research being conducted at UCCC, reflecting epidemiologic research on risk factors for breast cancer (papers 1-3 described below), chemoprevention Prevention & Control Principal Investigator / Program Director (Last, First, Middle): Byers, T.E. (P30 CA046934)
research involving colorectal and prostate cancer (papers 4,5), cancer screening research targeting prostate, colorectal and breast cancer (papers 6-11), and finally, tobacco control research (paper 12).
Wang C, Baumgartner RN, Yang D, Slattery ML, Murtaugh MA, Byers T (PC), Hines LM (PC), Giuliano AR, Baumgartner KB. No evidence of association between breast cancer risk and dietary carotenoids, retinols, vitamin C and tocopherols in Southwestern Hispanic and non-Hispanic White women. Breast Cancer Res Treat 114(1):137-145, 2009.
The effects of dietary intake of antioxidant vitamins on breast cancer risk are inconclusive. Moreover, little is known as to whether associations differ between non-Hispanic White (NHW) and Hispanic women. In this study, the investigators assessed the associations of the dietary intake of antioxidant vitamins commonly found in fruits and vegetables with breast cancer risk and estrogen receptor (ER) status among NHW and Hispanic women living in the Southwestern U.S. Primary breast cancer cases in the 4-Corners region (Arizona, Colorado, New Mexico, Utah), diagnosed between October 1999 and May 2004, were identified through state cancer registries. Controls were frequency matched by ethnicity and age (+/-5 years). Information on demographic characteristics and other breast cancer risk factors prior to the referent year were collected by interviewer-administered computerized questionnaire. A modified extensive diet history questionnaire was used to assess dietary intake. The investigators did not find a protective effect of dietary antioxidants, such as alpha or beta-carotene, beta-cryptoxanthin, lutein/zeaxanthin, lycopene, retinol, vitamin C, alpha, delta, beta or gamma-tocopherol, on breast cancer risk. In addition, they did not find any consistent associations with multivariate risk of breast cancer or estrogen receptor status.
Risendal B (PC), Hines LM (PC), Sweeney C, Slattery ML, Giuliano AR, Baumgartner KB, Curtin K, Byers TE (PC). Family history and age at onset of breast cancer in Hispanic and non-Hispanic white women. Cancer Causes Control 19(10):1349-1355, 2008.
The main objective of this study was to evaluate the association between family history of breast cancer and breast cancer risk among Hispanic and non-Hispanic white (NHW) women. Logistic regression models were used to compute unadjusted and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) using data collected from the 4-Corners Breast Cancer Study, a population-based case-control study of breast cancer conducted in the Southwest United States (3,074 NHW and 1,647 Hispanic women). The association between family history of breast cancer and early-onset breast cancer risk differed among NHW and Hispanic women. Among women <50 years old, having a family history of breast cancer was associated with a greater increase in risk among NHWs, with an OR of 2.34 (95% CI: 1.64-3.35) when compared to an OR of 1.32 (95% CI: 0.82-2.19) for Hispanics. This difference in risk was not observed among women 50 years and older, with an OR of 1.69 (95% CI: 1.34-2.13) for NHW and 1.47 (95% CI: 1.03-2.10) for Hispanics. Given these results, it would appear that family history of breast cancer poses a greater risk for early-onset breast cancers among NHW when compared to Hispanic women and may reflect ethnic differences in certain predisposing genetic factors that promote breast cancer development.
Hines LM (PC), Risendal B (PC), Slattery ML, Baumgartner KB, Giuliano AR, Byers T (PC). Differences in estrogen receptor subtype according to family history of breast cancer among Hispanic, but not non-Hispannic White women. Cancer Epidemiol Biomarkers Prev 17(10):2700-2706, 2008.
Pathologic differences have been reported among breast tumors when comparing ethnic populations. Limited research has been done to evaluate the ethnic-specific relationships between breast cancer risk factors and the pathologic features of breast tumors. Given that genetic variation may contribute to ethnic-related etiologic differences in breast cancer, the investigators hypothesized that tumor characteristics differ according to family history of breast cancer among Hispanic and non-Hispanic White (NHW) women. Logistic regression models were used to compute odds ratios (OR) and 95% confidence intervals (95% CI) to assess this relationship in the population-based, case-control 4-Corners Breast Cancer Study (1,537 cases and 2,452 controls). Among Hispanic women, having a family history was associated with a 2.7-fold increased risk of estrogen receptor (ER) negative (95% CI, 1.59-4.44), but not ER positive tumors (OR, 1.04; 95% CI, 0.71-1.54) when compared with women without breast cancer. In contrast, there was an increased risk for ER positive (OR, 1.89; 95% CI, 1.50-2.38) and a marginally significant increased risk for ER negative tumors (OR, 1.41; 95% CI, 0.92-2.17) among NHW women. When comparing tumor characteristics among invasive cases, those with a family history also had a significantly higher proportion of ER negative tumors among Hispanics (39.2% versus 25.8%; P=0.02), but not among NHWs (16.3% versus 21.1%; P=0.13). According to the authors, these results may reflect ethnic-specific predisposing genetic factors that promote the development of specific breast tumor subtypes, as well as highlighting the importance of evaluating the relationship between breast cancer risk factors and breast tumor subtypes among different ethnic populations.
Grau MV, Sandler RS, Keown-Eyssen G, Bresalier RS, Haile RW, Barry EL, Ahnen DJ (PC), Gui J, Summers RW, Baron JA. Nonsteroidal anti-inflammatory drug use after 3 years of aspirin use and colorectal adenoma risk: observational follow-up of a randomized study. J Natl Cancer Inst 101(4):267-276, 2009.
Frequent use of nonsteroidal anti-inflammatory drugs (NSAIDs) has been shown to reduce the risk of colorectal adenomas in randomized trials. In this study, the investigators examined the persistence of the protective effect after the cessation of randomized aspirin treatment and whether it was affected by the duration and frequency of subsequent NSAID use. Data from the Aspirin/Folate Polyp Prevention Study (AFPPS) were analyzed, in which 1121 subjects were randomly assigned to receive placebo or aspirin (81 or 325 mg/d) for 3 years. After the end of treatment and a follow-up colonoscopy, AFPPS participants were invited to remain under follow-up until their next surveillance colonoscopies, scheduled 3-5 years later. Information regarding use of NSAIDs during posttreatment follow-up was gathered periodically via questionnaires. Average weekly NSAID use was classified as sporadic (<2 days per week), moderate (2 to <4 days per week), or frequent (>or=4 days per week). The analysis was stratified according to randomized aspirin groups and posttreatment NSAID use; placebo subjects who later were sporadic NSAID users formed the reference group. The primary outcomes were all adenomas and advanced lesions. Adjusted relative risks and 95% confidence intervals were computed with generalized linear models. A total of 850 subjects underwent a posttreatment colonoscopy, on average 4 years after the end of study treatment. The protective effect of 81 mg of aspirin for colorectal adenomas persisted with continued posttreatment NSAID use. The risk of any adenoma among frequent NSAID users was 26.8% vs 39.9% among placebo subjects who later used NSAIDs sporadically (adjusted relative risk = 0.62, 95% confidence interval [CI] = 0.39 to 0.98; P(trend) with NSAID use frequency = .03). The unadjusted absolute risk reduction was 13.1 percentage points (95% CI = -0.3 to 26.5 percentage points) (P = .07). Results for 325 mg of aspirin were similar, although not statistically significant. For advanced lesions, small numbers of endpoints limited the analysis, but findings among subjects randomly assigned to 81 mg of aspirin suggested a protective association regardless of posttreatment NSAID use. Given these findings, it would appear that long-term and frequent use of NSAIDs may enhance the chemopreventive effect of aspirin against colorectal neoplasia.
Lippman SM, Klein EA, Goodman PJ, Lucia MS (HRM), Thompson IM, Ford LG, Parnes HL, Minasian LM, Gaziano JM, Hartline JA, Parsons JK, Bearden JD III, Crawford ED (HRM, PC), Goodman GE, Claudio J, Winquist E, Cook ED, Karp DD, Walther P, Lieber MM, Kristal AR, Darke AK, Arnold KB, Ganz PA, Santella RM, Albanes D, Taylor PR, Probstfield JL, Jagpal TJ, Crowley JJ, Meyskens FL Jr, Baker LH Coltman CA Jr. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 301(1):39-51, 2009.
Secondary analyses of 2 randomized controlled trials and supportive epidemiologic and preclinical data have indicated the potential of selenium and vitamin E for preventing prostate cancer. The main objective of this study was to determine whether selenium, vitamin E, or both could prevent prostate cancer and other diseases with little or no toxicity in relatively healthy men. A randomized, placebo-controlled trial was conducted involving 35,533 men from 427 participating sites in the United States, Canada, and Puerto Rico. In this trial, participants were randomly assigned to 4 groups (selenium, vitamin E, selenium + vitamin E, and placebo) in a double-blind fashion between August 22, 2001, and June 24, 2004. Baseline eligibility included age 50 years or older (African American men) or 55 years or older (all other men), a serum prostate-specific antigen level of 4 ng/mL or less, and a digital rectal examination not suspicious for prostate cancer. The interventions included oral selenium (200 microg/d from L-selenomethionine) and matched vitamin E placebo, vitamin E (400 IU/d of all rac-alpha-tocopheryl acetate) and matched selenium placebo, selenium + vitamin E, or placebo + placebo for a planned follow-up of 7 to 12 years. The main outcome measures included prostate cancer and prespecified secondary outcomes, including lung, colorectal, and overall primary cancer. As of October 23, 2008, median overall follow-up was 5.46 years (range, 4.17-7.33 years). Hazard ratios (99% confidence intervals [CIs]) for prostate cancer were 1.13 (99% CI, 0.95-1.35; n = 473) for vitamin E, 1.04 (99% CI, 0.87-1.24; n = 432) for selenium, and 1.05 (99% CI, 0.88-1.25; n = 437) for selenium + vitamin E vs 1.00 (n = 416) for placebo. There were no significant differences (all P>.15) in any other prespecified cancer end points. There were statistically nonsignificant increased risks of prostate cancer in the vitamin E group (P = .06) and type 2 diabetes mellitus in the selenium group (relative risk, 1.07; 99% CI, 0.94-1.22; P = .16) but not in the selenium + vitamin E group. Thus, selenium or vitamin E, alone or in combination at the doses and formulations used, did not prevent prostate cancer in this population of relatively healthy men.
Andriole GL, Crawford ED (HRM, PC), Grubb RL III, Buys SS, Chia D, Church TR, Fouad MN, Gelmann EP, Kvale PA, Reding DJ, Weissfeld JL, Yokochi LA, O'Brien B, Clapp JD, Rathmell JM, Riley TL, Hayes RB, Kramer BS, Izmirlian G, Miller AB, Pinsky PF, Prorok PC, Gohagan JK, Berg CD, PLCO Project Team. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med 360(13):1310-1319, 2009.
The effect of screening with prostate-specific-antigen (PSA) testing and digital rectal examination on the rate of death from prostate cancer is unknown. This is the first report from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial on prostate-cancer mortality. From 1993 through 2001, 76,693 men at 10 U.S. study centers were randomly assigned to receive either annual screening (38,343 subjects) or usual care as the control (38,350 subjects). Men in the screening group were offered annual PSA testing for 6 years and digital rectal examination for 4 years. The subjects and health care providers received the results and decided on the type of follow-up evaluation. Usual care sometimes included screening, as some organizations have recommended. The numbers of all cancers and deaths and causes of death were ascertained. In the screening group, rates of compliance were 85% for PSA testing and 86% for digital rectal examination. Rates of screening in the control group increased from 40% in the first year to 52% in the sixth year for PSA testing and ranged from 41 to 46% for digital rectal examination. After 7 years of follow-up, the incidence of prostate cancer per 10,000 person-years was 116 (2820 cancers) in the screening group and 95 (2322 cancers) in the control group (rate ratio, 1.22; 95% confidence interval [CI], 1.16 to 1.29). The incidence of death per 10,000 person-years was 2.0 (50 deaths) in the screening group and 1.7 (44 deaths) in the control group (rate ratio, 1.13; 95% CI, 0.75 to 1.70). The data at 10 years were 67% complete and consistent with these overall findings. Based on these findings, the authors concluded that after 7 to 10 years of follow-up, the rate of death from prostate cancer was very low and did not differ significantly between the two study groups.
Grubb RL III, Black A, Izmirlian G, Hickey TP, Pinsky PF, Mabie JE, Riley TL, Ragard LR, Prorok PC, Berg CD, Crawford ED (HRM, PC), Church TR, Andriole GL Jr, PLCO Project Team. Serum prostate-specific antigen hemodilution among obese men undergoing screening in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Cancer Epidemiol Biomarkers Prev 18(3):748-751, 2009.
Previous studies have shown an inverse relationship between prostate-specific antigen (PSA) concentration and body mass index (BMI). It has been recently proposed that this relationship may be explained by the larger plasma volume of obese men diluting a fixed amount of PSA (hemodilution effect). This hypothesis was examined in a cohort of men enrolled in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Of 38,349 men ages 55 to 74 years randomized in PLCO to receive annual PSA and digital rectal examination screening, 28,380 had a baseline PSA, complete demographic information, and no prostate cancer diagnosis within 6 years from baseline. Self-reported height and weight were used to calculate BMI and to estimate plasma volume. PSA mass was estimated as PSA concentration times plasma volume. Multivariable linear regression models were used to investigate the relationship between PSA concentration, plasma volume, PSA mass, and BMI. PSA concentration significantly decreased with increasing BMI (P<0.001); mean PSA values were 1.27, 1.25, 1.18, and 1.07 ng/mL among normal (BMI, 18.5-25), overweight (BMI, 25-30), obese (BMI, 30-35), and morbidly obese (BMI, >35) men, respectively. However, plasma volume also increased with increasing BMI and PSA mass showed no association with BMI, with mean values of 3.78, 3.95, 3.97, and 3.82 microg across the four BMI categories (P=0.10). Thus, this study confirmed earlier findings that the inverse relationship between PSA concentration and BMI may be explained by a hemodilution effect. These findings could have implications for prostate cancer screening in large men.
Zou H, Taylor WR, Harrington JJ, Hussain FT, Cao X, Loprinzi CL, Levine TR, Rex DK, Ahnen D (PC), Knigge KL, Lance P, Jiang X, Smith DI, Ahlquist DA. High detection rates of colorectal neoplasia by stool DNA testing with a novel digital melt curve assay. Gastroenterology 136(2):459-470, 2009.
Current stool DNA tests identify about half of individuals with colorectal cancers and miss most individuals with advanced adenomas. The investigators developed a digital melt curve (DMC) assay to quantify low-abundance mutations in stool samples for detection of colorectal neoplasms and compared this test with other approaches. A melt curve assay was combined with digital polymerase chain reaction and validated the quantitative range. The investigators then evaluated its ability to detect neoplasms in 2 clinical studies. In study I, stool samples from patients with colorectal tumors with known mutations (KRAS, APC, BRAF, TP53) were assayed. In study II, archived stool samples from patients with advanced adenomas containing known KRAS mutations were assayed, along with controls. Results were compared with those from the stool DNA test PreGenPlus (Exact Sciences, Marlborough, MA), Hemoccult, and HemoccultSensa (both Beckman-Coulter, Fullerton, CA). The DMC assay detected samples in which only 0.1% of target genes were mutated. In study I, the DMC assay detected known mutations in 28 (90%) of 31 tumor samples and 6 (75%) of 8 advanced adenoma samples. In study II, the DMC assay detected 16 (59%) of 27 advanced adenoma samples that contained KRAS mutations, compared with 7% with the Hemoccult, 15% with the HemoccultSensa, and 26% with the PreGenPlus assays (P < .05 for each, compared with the DMC assay); specificities did not differ significantly. While acknowledging the need for more research, the investigators concluded that the DMC assay has a high level of sensitivity in detecting individuals with colon neoplasms and is better than current stool screening methods in detecting those with advanced adenomas.
Ahlquist DA, Sargent DJ, Loprinzi CL, Levin TR, Rex DK, Ahnen DJ (PC), Knigge K, Lance MP, Burgart LJ, Hamilton SR, Allison JE, Lawson MJ, Devens ME, Harrington JJ, Hillman SL. Stool DNA and occult blood testing for screen-detection of colorectal neoplasia: A prospective multi-center comparison. Ann Intern Med 149(7):441-450, 2008.
Stool DNA testing is a new approach to colorectal cancer detection; however, few data are available from the screening setting. The main objective of this study was to compare stool DNA and fecal blood testing for detection of screen-relevant neoplasia (curable-stage cancer, high-grade dysplasia, or adenomas >1 cm). A blinded, multicenter, cross-sectional study was conducted. Participants included 4482 average-risk adults. Participants collected 3 stools, smeared fecal blood test cards and used same-day shipment to a central facility. Fecal blood cards (Hemoccult and HemoccultSensa, Beckman Coulter, Fullerton, California) were tested on 3 stools and DNA assays on 1 stool per patient. Stool DNA test 1 (SDT-1) was a precommercial 23-marker assay, and a novel test (SDT-2) targeted 3 broadly informative markers. The criterion standard was colonoscopy. Sensitivity for screen-relevant neoplasms was 20% by SDT-1, 11% by Hemoccult (P = 0.020), 21% by HemoccultSensa (P = 0.80); sensitivity for cancer plus high-grade dysplasia did not differ among tests. Specificity was 96% by SDT-1, compared with 98% by Hemoccult (P < 0.001) and 97% by HemoccultSensa (P = 0.20). Stool DNA test 2 detected 46% of screen-relevant neoplasms, compared with 16% by Hemoccult (P < 0.001) and 24% by HemoccultSensa (P < 0.001). Stool DNA test 2 detected 46% of adenomas 1 cm or larger, compared with 10% by Hemoccult (P < 0.001) and 17% by HemoccultSensa (P < 0.001). Among colonoscopically normal patients, the positivity rate was 16% with SDT-2, compared with 4% with Hemoccult (P = 0.010) and 5% with HemoccultSensa (P = 0.030). The investigators concluded from this analysis that stool DNA test 1 provides no improvement over HemoccultSensa for detection of screen-relevant neoplasms, while stool DNA test 2 detects significantly more neoplasms than does Hemoccult or HemoccultSensa, but with more positive results in colonoscopically normal patients. Higher sensitivity of SDT-2 was particularly apparent for adenomas.
Feldstein AC, Perrin N, Rosales AG, Schneider J, Rix MM, Keels K, Schoap S, Glasgow RE (PC). Effect of a multimodal reminder program on repeat mammogram screening. Am J Prev Med 37(2):94-101, 2009.
Patient mammogram reminders are effective but have not been fully implemented in practice to improve routine screening. The effectiveness of implementation and maintenance phases of a multimodal reminder program that incorporated automated calls capable of efficiently reaching large numbers of women was evaluated to improve repeat mammography screening. A quasi-experimental study was conducted using electronic medical record data during three time periods: pre-reminder phase (2004), post-reminder implementation phase (2006), and post-reminder maintenance phase (January 1-July 1, 2007). Participants were female Kaiser Permanente Northwest HMO members aged 42 years or more who were 20 months past their last mammogram (index date) (N=35,104). The intervention program targeted women aged 50-69 years. Women aged 42-49 years (for whom clinical guidelines also recommend mammography) not targeted by the program constituted the primary comparison group. A "mammogram due soon" postcard was mailed to participants 20 months after their last mammogram, followed by up to two automated phone calls and one live call for nonresponders. The outcome measure was the time until participants received a mammogram in the 10 months following the index date. During the pre-reminder phase, 63.4% of targeted women completed a mammogram; this number increased to 75.4% in the post-reminder phase; 80.6% completed a mammogram in the maintenance phase. After controlling for demographics and clinic visits, intervention women were 1.51 times more likely to complete a mammogram (CI=1.40, 1.62) post-reminder compared to the control group. The effect was maintained in 2007 (hazard ratio 1.81, CI=1.65, 1.99). Given these findings, this study demonstrated that this multimodal reminder system could be effectively implemented and maintained in a large health system. If widely implemented, this intervention could substantially improve community mammography screening.
Robertson DJ, Burke CA, Welch HG, Haile RW, Sandler RS, Greenberg ER, Ahnen DJ (PC), Bresalier RS, Rothstein RI, Cole B, Mott LA, Baron JA. Using the results of a baseline and a surveillance colonoscopy to predict recurrent adenomas with high-risk characteristics. Ann Intern Med 151(2):103-109, 2009.
Suggested intervals for postpolypectomy surveillance colonoscopy are currently based on the adenoma findings from the most recent examination. The main objective of this study was to determine the risk for clinically significant adenoma recurrence on the basis of the results of 2 previous colonoscopies. A prospective cohort study was conducted involving participants in an adenoma chemoprevention trial. All participants had 1 or more adenoma found on complete colonoscopy at entry. For this analysis, only participants whose qualifying adenoma was their first were included. All participants then underwent second and third study colonoscopies at roughly 3-year intervals. The main endpoint in this study was the proportion of patients with high-risk findings at the third study colonoscopy--either at least 1 advanced (> or = 1 cm or advanced histology) adenoma or multiple (> or = 3) adenomas. Fifty-eight of 564 participants (10.3%) had high-risk findings at the third study examination. If the second examination showed high-risk findings, then results from the first examination added no significant information about the probability of high-risk findings on the third examination (18.2% for high-risk findings on the first examination vs. 20.0% for low-risk findings on the first examination; P = 0.78). If the second examination showed no adenomas, then the results from the first examination added significant information about the probability of high-risk findings on the third examination (12.3% if the first examination had high-risk findings vs. 4.9% if the first examination had low-risk findings; P = 0.015). The authors concluded from this analysis that information from 2 previous examinations may help identify low-risk populations that benefit little from intense surveillance. Surveillance guidelines might then be tailored in selected patients to use information from 2 previous examinations, not just the most recent one.
Glasgow RE (PC), Gaglio B, Estabrooks PA, Marcus AC (PC), Ritzwoller DP, Smith TL, Levinson AH (PC), Sukhanova A, O'Donnell C, Ferro EF, France EK. Long-term results of a smoking reduction program. Med Care 47(1):115-120, 2009.
There have been few comprehensive evaluations of smoking reduction, especially in health care delivery systems, and little is known about its cost, maintenance of reduced smoking, or robustness across patient subgroups. A representative sample of 320 adult smokers from an HMO scheduled for outpatient surgery or a diagnostic procedure was randomized to enhanced usual care or a theory-based smoking reduction intervention that combined telephone counseling and tailored newsletters. Outcomes included cigarettes smoked, carbon monoxide levels, and costs. Both intervention and control conditions continued to improve from 3- to 12-month assessments. Between-condition differences using intent-to-treat analyses on both self-report and carbon monoxide measures were nonsignificant by the 12-month follow-up (25% vs. 19% achieved 50% or greater reductions in cigarettes smoked). The intervention was implemented consistently despite logistical constraints and was generally robust across patient characteristics (eg, education, ethnicity, health literacy, dependence). The authors concluded from this study that in the absence of nicotine replacement therapy, the long-term effects of this smoking reduction intervention were modest and nonsignificant, and that future research is indicated to enhance intervention effects.
Promoting Collaborations The Prevention & Control Program continues to promote inter- and intra-programmatic collaborations at UCCC through program participation in the on-going UCCC Symposium Series and sponsoring other cancer-related seminars. For example, during 2008-2009 relevant presentations included seminars conducted by Dr. Tom Denberg ("Health Promotion Outreach for Colorectal and Prostate Cancer"), Dr. Ann Zauber from Memorial Sloan-Kettering Cancer Center ("Population-Based Modeling to Inform Health Policy for Colorectal Cancer Screening"), Dr. Tim Byers ("Social Class and Cancer in Colorado and the Nation"), Dr. Wendy Demark-Wahnefried from MD Anderson Cancer Center ("Diet and Exercise: Interventions for Cancer Prevention and Control"), Dr. Anna Giuliano from the Moffitt Cancer Center ("HPV Infection in Males: The Potential for Vaccine Approach to Cancer Prevention"), as well as a symposium on cancer survivorship ("Developing Clinical Programs for Cancer Survivors as a Distinct Phase of Cancer Care") that included Ms. Mary McCabe (Memorial Sloan-Kettering Cancer Center), Dr. Linda Jacobs (Abramson Cancer Center, University of Pennsylvania), and Dr. Jean Kutner.
Another key avenue for promoting research collaborations involves participation in the Colorado Cancer Coalition (CCC), including the various CCC subcommittees, and providing expert consultation in the development of the Colorado Cancer Control Plan by the Colorado Department of Public Health and Environment. Both of these strategic planning efforts focus on developing guidelines and priorities for both service and research. Program members who have been active in these activities include Drs. Byers, Marcus, Buller, Crane, Levinson, Calonge and Espinoza, among others. Of special note is that Dr. Marcus is serving as the chair of a new Cancer Survivorship Task Force within the CCC. Among the main objectives of this task force is to expand cancer survivorship resources and educational opportunities, encourage and facilitate the development of new clinical programs for cancer survivors, promote the dissemination of treatment summaries and care plans to cancer survivors, and secure additional funding for cancer survivorship service programs and research statewide.
Finally, the Program Leadership and other program members routinely monitor program announcements, RFAs, RFPs and other funding opportunities from the NCI, ACS, CDC, and elsewhere to facilitate ad hoc planning meetings, and to coordinate and facilitate a competitive response to these opportunities. Similarly, Program Leadership routinely organizes other ad hoc meetings and provides administrative, technical and scientific support to facilitate investigator-initiated proposals that would either renew an existing program of research, or initiate a new or emerging program of research that would leverage the strengths and previous research of investigators aligned with Prevention & Control. Several recent examples of this process include the patient navigation research program of Dr. Raich, the LIVESTRONG Center of Excellence grant, the program project grant involving the Cancer Information Service Research Consortium, and Dr. Byers’ longitudinal cohort study of Latina and Anglo breast cancer cases and controls.
Grants and Contracts This program’s members’ active portfolio of grants and contracts highlight several essential themes that characterize the future research interests and priorities of the Program, including: a) reducing cancer-related disparities in the Rocky Mountain Region and beyond, with a particular focus on Hispanics and African Americans; b) cancer survivorship and patient navigation programs as a high priority area of research, including the implementation of two new clinical programs for cancer survivors, c) a particular focus on promoting cancer screening among high risk populations, d) tobacco control research, e) continuing our highly productive collaboration with the NCI’s CIS in health communications research, and f) conducting intervention research that has significant potential for dissemination as usual service programs, both regionally and nationally. What follows are brief descriptions of thirteen of these grant and contract awards.Prevention & Control Principal Investigator / Program Director (Last, First, Middle): Byers, T.E. (P30 CA046934)
1) The LIVESTRONG Survivorship Center of Excellence (Dr. Alison Jones, Principal Investigator): Funded by the Lance Armstrong Foundation in 2006, this five year grant established a LIVESTRONG Survivorship Center of Excellence at UCCC. This Center is serving as the focal point for coordinating and expanding all cancer patient and survivor support services at UCCC, as well as expanding cancer patient and survivor support services at three community-based centers in Colorado (i.e., Denver Health Medical Center, St Mary-Corwin Medical Center in Pueblo, Colorado, and St. Mary’s Medical Center in Grand Junction, Colorado). Included among the support services that are being enhanced or expanded as part of this Center are on-site patient and survivor educational programs and workshops, dedicated Cancer Resource Centers at each collaborating institution (library of print materials with Intranet access to online resources), proactive telephone outreach and counseling to cancer patients and survivors, and continuing medical education seminars and programs in cancer survivorship offered to medical and other professional staff (especially at the three community-based centers). In addition, a new transition clinic for adult survivors of childhood cancer was launched at UCCC in 2008 in collaboration with The Children’s Hospital (Denver), and a similar clinic for survivors of adult cancer was launched in 2009 for survivors of adult cancer. Both clinics are using a one-visit consultative model.
2) Cancer Information Service Research Consortium (Dr. Al Marcus, Principal Investigator): Funded as a NCI program project grant in collaboration with NCI’s Cancer Information Service (CIS), three interrelated component projects are testing a state-of-the-science web-based multimedia program for newly diagnosed prostate cancer patients (Project 1), newly diagnosed breast cancer patients (Project 2) and breast cancer patients completing their primary treatment for breast cancer (Project 3). All program participants are being recruited from the CIS telephone service at the end of their usual service call to the CIS. A second intervention that is being tested for efficacy involves Information Specialists from the CIS making a scheduled outcall to program participants (Project 3 only). Major outcomes for program evaluation include treatment decision-making, cancer-specific distress and depression, and cancer-related quality of life. This program project, which was funded in 2006, represents the third such program project conducted in collaboration with the CIS. Collaborating institutions (with the UCCC) include the Fox Chase Cancer Center, the Jonsson Comprehensive Cancer Center at UCLA and Mount Sinai Medical Center.
3) Understanding and Improving Breast Cancer Survivorship in Latinas (Dr. Tim Byers, Principal Investigator): In this longitudinal cohort study, approximately 1,000 participants in the Southwest Hormone, Insulin, Nutrition and Exercise (SHINE) Women’s Health Study have been re-interviewed. The sample includes about 275 Hispanic and non-Hispanic White breast cancer survivors (cases), and a similar number of Hispanic and non-Hispanic White controls. Assessments that have been added to the original SHINE cohort study include diet, physical activity, quality of life, and health care system interactions. When completed, this will be one of the largest studies of breast cancer survivorship among Hispanics in this country.
4) Patient Navigator Research Program (Dr. Peter Raich, Principal Investigator): Funded in response to RFA CA-05-019, this randomized trial is testing an innovative patient navigation program at Denver Health Medical Center, targeting patients from the point of an abnormal screening test to treatment for breast, colorectal and prostate cancers. Innovative features of this patient navigation program include: a) building upon an existing on-site and community-based patient navigation program involving lay health workers (i.e., Community Voices), b) combining this program with a proactive telephone counseling service, and c) integrating both of these program components within a large public-supported medical center, where a large percentage of eligible patients will be Hispanic and underserved. Major outcomes for program evaluation will include accelerating the time between an abnormal screening test and diagnostic follow-up, on-set of therapy (for cancer patients), adherence to treatment and completion of treatment, as well as improving patient-reported outcomes (e.g., self-efficacy, satisfaction, psychosocial outcomes).
5) Metro Denver Black Church Initiative (Dr. Al Marcus, Principal Investigator): Funded by the National Center for Minority Health and Health Disparities, this project involves implementing a program of community-based participatory research to promote diet, nutrition, physical activity and cancer screening among African Americans living in Northeast Denver. The major community partner in this effort is the Center for African American Health, which has formed a consortium consisting of 35-40 primarily African American churches in Northeast Denver. A two-arm randomized pilot study is being implemented involving church members Prevention & Control Principal Investigator / Program Director (Last, First, Middle): Byers, T.E. (P30 CA046934) PHS 398/2590 (Rev. 06/09) Page Continuation Format Page 189
from six churches (three churches per arm), where the church is providing the venue for the intervention. Outcome measures include changes in BMI, blood pressure, physical fitness (step test) and self-reported cancer screening. It is anticipated that this pilot study will evolve into a larger efficacy trial.
6) The Colorado Colorectal Screening Program (Dr. Tim Byers, Principal Investigator): In September, 2006, the Colorado Colorectal Screening Program received a $3 million grant to provide colon cancer screening for uninsured residents of Colorado. The funding for this initiative comes from the tax increase on tobacco products in Colorado. This grant was subsequently renewed in July, 2008 for another $4.5 million. This landmark initiative, which could provide a model program for the nation, is supporting colorectal cancer screening across all community clinics in Colorado, targeting patients who are uninsured and 250% below the Federal poverty level. Eligible patients are being screened by sigmoidoscopy or colonoscopy, with the long-range goal of screening 12,500 Coloradans by 2010. Accompanying this screening outreach program is an awareness and promotion campaign to encourage all age-appropriate residents to seek colorectal cancer screening.
7) Psychoeducational Intervention for BMT Caregivers (Dr. Mark Laudenslager, Principle Investigator): Funded by the NCI in 2008 in response to PA-07-046 ("Research on Mind-Body Interactions and Health"), a two-arm randomized trial will be conducted comparing usual care vs. a stress management and psychoeducational intervention that will target the caregivers of patients receiving allogeneic blood and marrow transplants. Outcome measures will include caregiver health, immune and endocrine markers, physical activity and sleep characteristics, as well as stress and mood disturbance.
8) Smoking Cessation Navigation Pilot Study (Dr. Arnold Levinson, Principal Investigator): Funded by the NCI this year as a R21, this pilot study will test for feasibility the use of a smoking cessation navigator to increase initiation and completion of proven smoking cessation strategies (e.g., nicotine replacement therapy, quit line coaching), and biochemically validated abstinence rates. The main target group will be low income smokers. Navigation cost data will also be collected and analyzed pursuant to a future randomized trial.
9) Promoting Breast Cancer Screening in Women Who Survived Childhood Cancer (Dr. Kevin Oeffinger, Principal Investigator): Also funded this year as a R01, this five year randomized trial will test for efficacy a telephone counseling intervention to promote screening mammography. The target group will be young women (ages 25-39) who are survivors of childhood cancer and were treated with chest radiation. The sample will be recruited from the Childhood Cancer Survivor Study cohort. Dr. Oeffinger is affiliated with Memorial Sloan-Kettering Cancer Center (MSKCC). Dr. Al Marcus and colleagues from UCCC will develop and implement the telephone counseling intervention via a subcontract from MSKCC.
10) Colorado Front Range Community Network Project (CO-CNP) (Dr. Paula Espinoza, Principal Investigator): Funded by the NCI in 2005, the goal of the CO-CNP is to reduce cancer health disparities among Colorado Front Range Latinos. CO-CNP includes a pilot project program, a junior investigator training program, a cancer education program and an undergraduate education research opportunity program. CO-CNP recently funded three pilot projects as follows: "Developing a Navigation System for Latinos with Lung Cancer and Head and Neck Cancers" (Dr. Evelinn Borrayo, PI); "Formative Research on Latinos and Leaders on HPV Vaccine Acceptance and Promotion" (Ms. Patricia Valverde, PI), and "Targeting Tobacco Cessation Intervention for Latino/as with Depression" (Dr. Jeanette Waxmonsky, PI). The CO-CNP comes up for competitive renewal in 2010.
11) Promoting Colonoscopic Screening Among High Risk Families (Dr. Dennis Ahnen, Principal Investigator): Funded by the NCI in 2005, this large-scale randomized trial is testing a telephone counseling intervention to promote colonoscopies among families at high risk for colorectal cancer. This multisite randomized trial recruited high risk family members from the NCI-funded Cancer Genetics Network and the Collaborative Family Registry for Colorectal Cancer Studies. Follow-up occurred at 6, 12 and 24 months post-enrollment. This study is now in the analytic phase.
12) The Colorado Prevention and Control Research Network (CPRCN) (Dr. Betsy Risendal, Principal Investigator): Recently funded (2009) by the CDC, the goal of the CPRCN is to effectively translate Prevention & Control Principal Investigator / Program Director (Last, First, Middle): Byers, T.E. (P30 CA046934) PHS 398/2590 (Rev. 06/09) Page Continuation Format Page 190
evidence-based health promotion interventions to providers and the community to improve cancer survivorship and reduce health disparities in cancer outcomes. Among the high priority areas for dissemination, evaluation and education are evidence-based programs in diet, nutrition, weight management and physical activity for cancer survivors.
13) Quality of Life and Health Behavior in Long-Term Colon Cancer Survivors (D. Betsy Risendal, Principal Investigator): Funded by the ACS in 2009, this longitudinal cohort study will re-interview by telephone 500 probands and 500 non-cancer controls from the NCI-funded Colon Cancer Family Registry who were initially enrolled in 1998-2003. Among the endpoints that will be compared in this study (cases vs. controls) will be quality of life, mood disturbance, cancer-specific distress, fatigue, as well as diet, nutrition and physical activity practices.