Cyclin D1 in non-small cell lung cancer: a key driver of malignant transformation

PURPOSE: To review the evidence implicating the deregulation of cyclin D1 in the pathogenesis of non-small cell lung cancer (NSCLC), and to discuss the opportunities for targeted clinical intervention. METHODS: Data published until June 2006 are summarized, and previously unpublished results from our own research are included. RESULTS: In normal cells, cyclin D1 complexes with and activates cyclin-dependent kinases (CDK) and acts as a transcriptional regulator. The protein is frequently overexpressed in a wide range of cancers, sometimes coincident with CCND1 (cyclin D1) gene amplification (5-20% of tumours). A low level of somatic mutations have been seen in certain tumours. CCND1 is amplified in NSCLC and cyclin D1 is frequently overexpressed in tumours and pre-invasive bronchial lesions, generally from one parental allele. Mutation analyses revealed a frequent CCND1 gene polymorphism (A870G) that modulates alternative splicing and allows expression of an alternative cyclin D1 transcript (transcript cyclin D1b). The encoded cyclin D1b protein lacks a specific phosphorylation site required for nuclear export. Genotype has been correlated with the risk and/or severity of disease or drug response across a range of malignancies, including lung cancer. Together, these findings suggest a strong pathological role for cyclin D1 deregulation in bronchial neoplasia. CONCLUSION: Current data indicate that cyclin D1 overexpression is not a consequence of, but rather a pivotal element in the process of malignant transformation in the lung and other tissues. This understanding may open new avenues for lung cancer diagnosis, treatment and prevention.

Serum levels of mannose-binding lectin and the risk of fever in neutropenia pediatric cancer patients

BACKGROUND: Fever in neutropenia (FN) is a frequent complication in pediatric oncology. Deficiency of mannose-binding lectin (MBL), an important component of innate immunity, is common due to genetic polymorphisms, but its impact on infections in oncologic patients is controversial. This study investigated whether MBL serum levels at cancer diagnosis are associated with the development of FN in pediatric cancer patients. PROCEDURE: Serum MBL was measured using ELISA. Frequency, duration, and cause of FN were assessed retrospectively. Association with MBL level was analyzed using uni- and multivariate Poisson regression taking into account both intensity and duration of chemotherapy. RESULTS: In 94 children, with a cumulative follow-up time of 81.7 years, 177 FN episodes were recorded. Patients with both very low MBL levels (<100 microg/L; risk ratio (RR), 1.93; 95% CI, 1.14-3.28; P = 0.014) and normal MBL levels (>/=1,000 microg/L; RR, P = 0.011) had significantly more frequent FN episodes than patients with low MBL levels (100-999 microg/L). Patients with very low MBL levels had significantly more episodes of FN with severe bacterial infection (bacteremia or pneumonia; RR, 4.49; 1.69 = 11.8; P = 0.003), while those with normal MBL levels had more FN episodes with no microbial etiology identified (RR, 1.85; 1.14 = 3.03; P = 0.014). CONCLUSIONS: Very low MBL levels are associated with more frequent FN episodes, mainly due to severe bacterial infections. The surprising finding that children with normal MBL levels had more frequent FN episodes than those with low MBL levels needs testing in prospective studies. Pediatr Blood Cancer (c) 2006 Wiley-Liss, Inc.

H-ficolin serum concentration and susceptibility to fever and neutropenia in paediatric cancer patients

H-ficolin (Hakata antigen, ficolin-3) activates the lectin pathway of complement similar to mannose-binding lectin. However, its impact on susceptibility to infection is currently unknown. This study investigated whether the serum concentration of H-ficolin at diagnosis is associated with fever and neutropenia (FN) in paediatric cancer patients. H-ficolin was measured by time-resolved immunofluorometric assay in serum taken at cancer diagnosis from 94 children treated with chemotherapy. The association of FN episodes with H-ficolin serum concentration was analysed by multivariate Poisson regression. Median concentration of H-ficolin in serum was 26 mg/l (range 6-83). Seven (7%) children had low H-ficolin (< 14 mg/l). During a cumulative chemotherapy exposure time of 82 years, 177 FN episodes were recorded, 35 (20%) of them with bacteraemia. Children with low H-ficolin had a significantly increased risk to develop FN [relative risk (RR) 2.24; 95% confidence interval (CI) 1.38-3.65; P = 0.004], resulting in prolonged duration of hospitalization and of intravenous anti-microbial therapy. Bacteraemia occurred more frequently in children with low H-ficolin (RR 2.82; CI 1.02-7.76; P = 0.045). In conclusion, low concentration of H-ficolin was associated with an increased risk of FN, particularly FN with bacteraemia, in children treated with chemotherapy for cancer. Low H-ficolin thus represents a novel risk factor for chemotherapy-related infections.

Incident malignancies among older long-term breast cancer survivors and an age-matched and site-matched nonbreast cancer comparison group over 10 years of follow-up

BACKGROUND Of the approximately 2.4 million American women with a history of breast cancer, 43% are aged ≥ 65 years and are at risk for developing subsequent malignancies. METHODS Women from 6 geographically diverse sites included 5-year breast cancer survivors (N = 1361) who were diagnosed between 1990 and 1994 at age ≥ 65 years with stage I or II disease and a comparison group of women without breast cancer (N = 1361). Women in the comparison group were age-matched and site-matched to breast cancer survivors on the date of breast cancer diagnosis. Follow-up began 5 years after the index date (survivor diagnosis date or comparison enrollment date) until death, disenrollment, or through 15 years after the index date. Data were collected from medical records and electronic sources (cancer registry, administrative, clinical, National Death Index). Analyses included descriptive statistics, crude incidence rates, and Cox proportional hazards regression models for estimating the risk of incident malignancy and were adjusted for death as a competing risk. RESULTS Survivors and women in the comparison group were similar: >82% were white, 55% had a Charlson Comorbidity Index of 0, and ≥ 73% had a body mass index ≤ 30 kg/m(2) . Of all 306 women (N = 160 in the survivor group, N = 146 in the comparison group) who developed a first incident malignancy during follow-up, the mean time to malignancy was similar (4.37 ± 2.81 years vs 4.03 ± 2.76 years, respectively; P = .28), whereas unadjusted incidence rates were slightly higher in survivors (1882 vs 1620 per 100,000 person years). The adjusted hazard of developing a first incident malignancy was slightly elevated in survivors in relation to women in the comparison group, but it was not statistically significant (hazard ratio, 1.17; 95% confidence interval, 0.94-1.47). CONCLUSIONS Older women who survived 5 years after an early stage breast cancer diagnosis were not at an elevated risk for developing subsequent incident malignancies up to 15 years after their breast cancer diagnosis.

Serum Concentrations of Mannan-Binding Lectin (MBL) and MBL-Associated Serine Protease-2 and the Risk of Adverse Events in Pediatric Patients With Cancer and Fever in Neutropenia

Background. It is unknown whether serum concentrations of mannan-binding lectin (MBL) and MBL-associated serine protease-2 (MASP-2) influence the risk of adverse events (AEs) in children with cancer presenting with fever in neutropenia (FN). Methods. Pediatric patients with cancer presenting with FN after non-myeloablative chemotherapy were observed in a prospective multicenter study. Mannan-binding lectin and MASP-2 were measured using commercially available enzyme-linked immunosorbent assay in serum taken at cancer diagnosis. Multiple FN episodes per patient were allowed. Associations of MBL and MASP-2 with AE in general, with bacteremia, and with serious medical complications (SMC) during FN were analyzed using mixed logistic regression. Results. Of 278 FN episodes, AE was reported in 84 (30%), bacteremia was reported in 42 (15%), and SMC was reported in 16 (5.8%). Median MBL was 2152 ng/mL (range, 7–10 060). It was very low (<100) in 11 (9%) patients, low (100–999) in 36 (29%) patients, and normal (�1000) in 79 (63%) patients. Median MASP-2 was 410 ng/mL (range, 68–2771). It was low (<200) in 18 (14%) patients and normal in the remaining 108 (86%) patients. Mannan-binding lectin and MASP-2 were not significantly associated with AE or bacteremia. Normal versus low MBL was independently associated with a significantly higher risk of SMC (multivariate odds ratio, 12.8; 95% confidence interval, 1.01–163; P = .050). Conclusions. Mannan-binding lectin and MASP-2 serum concentrations were not found to predict the risk to develop AEs or bacteremia during FN. Normal MBL was associated with an increased risk of SMC during FN. This finding, in line with earlier studies, does not support the concept of MBL supplementation in MBL-deficient children with cancer presenting with FN.

Risk factors for anal cancer in persons infected with HIV: a nested case-control study in the Swiss HIV Cohort Study

Although persons infected with human immunodeficiency virus (HIV), particularly men who have sex with men, are at excess risk for anal cancer, it has been difficult to disentangle the influences of anal exposure to human papillomavirus (HPV) infection, immunodeficiency, and combined antiretroviral therapy. A case-control study that included 59 anal cancer cases and 295 individually matched controls was nested in the Swiss HIV Cohort Study (1988-2011). In a subset of 41 cases and 114 controls, HPV antibodies were tested. A majority of anal cancer cases (73%) were men who have sex with men. Current smoking was significantly associated with anal cancer (odds ratio (OR) = 2.59, 95% confidence interval (CI): 1.25, 5.34), as were antibodies against L1 (OR = 4.52, 95% CI: 2.00, 10.20) and E6 (OR = ∞, 95% CI: 4.64, ∞) of HPV16, as well as low CD4+ cell counts, whether measured at nadir (OR per 100-cell/μL decrease = 1.53, 95% CI: 1.18, 2.00) or at cancer diagnosis (OR per 100-cell/μL decrease = 1.24, 95% CI: 1.08, 1.42). However, the influence of CD4+ cell counts appeared to be strongest 6-7 years prior to anal cancer diagnosis (OR for <200 vs. ≥500 cells/μL = 14.0, 95% CI: 3.85, 50.9). Smoking cessation and avoidance of even moderate levels of immunosuppression appear to be important in reducing long-term anal cancer risks.

NOVEL AMINO ACID TRANSPORTER-TARGETED RADIOTRACERS FOR BREAST CANCER IMAGING

Breast cancer is the most common malignancy among women in the world. Its 5-year survival rate ranges from 23.4% in patients with stage IV to 98% in stage I disease, highlighting the importance of early detection and diagnosis. 18F-2-Fluoro-2-deoxy-glucose (18F-FDG), using positron emission tomography (PET), is the most common functional imaging tool for breast cancer diagnosis currently. Unfortunately, 18F-FDG-PET has several limitations such as poorly differentiating tumor tissues from inflammatory and normal brain tissues. Therefore, 18F-labeled amino acid-based radiotracers have been reported as an alternative, which is based on the fact that tumor cells uptake and consume more amino acids to sustain their uncontrolled growth. Among those radiotracers, 18F-labeled tyrosine and its derivatives have shown high tumor uptake and great ability to differentiate tumor tissue from inflammatory sites in brain tumors and squamous cell carcinoma. They enter the tumor cells via L-type amino acid transporters (LAT), which were reported to be highly expressed in many cancer cell lines and correlate positively with tumor growth. Nevertheless, the low radiosynthesis yield and demand of an on-site cyclotron limit the use of 18F-labeled tyrosine analogues. In this study, four Technetium-99m (99mTc) labeled tyrosine/ AMT (α-methyl tyrosine)-based radiotracers were successfully synthesized and evaluated for their potentials in breast cancer imaging. In order to radiolabel tyrosine and AMT, the chelators N,N’-ethylene-di-L-cysteine (EC) and 1,4,8,11-tetra-azacyclotetradecane (N4 cyclam) were selected to coordinate 99mTc. These chelators have been reported to provide stable chelation ability with 99mTc. By using the chelator technology, the same target ligand could be labeled with different radioisotopes for various imaging modalities for tumor diagnosis, or for internal radionuclide therapy in future. Based on the in vitro and in vivo evaluation using the rat mammary tumor models, 99mTc-EC-AMT is considered as the most suitable radiotracer for breast cancer imaging overall, however, 99mTc-EC-Tyrosine will be more preferred for differential diagnosis of tumor from inflammation.

Cancer risk and use of protease inhibitor or nonnucleoside reverse transcriptase inhibitor-based combination antiretroviral therapy: the d: a: d study.

BACKGROUND The association between combination antiretroviral therapy (cART) and cancer risk, especially regimens containing protease inhibitors (PIs) or nonnucleoside reverse transcriptase inhibitors (NNRTIs), is unclear. METHODS Participants were followed from the latest of D:A:D study entry or January 1, 2004, until the earliest of a first cancer diagnosis, February 1, 2012, death, or 6 months after the last visit. Multivariable Poisson regression models assessed associations between cumulative (per year) use of either any cART or PI/NNRTI, and the incidence of any cancer, non-AIDS-defining cancers (NADC), AIDS-defining cancers (ADC), and the most frequently occurring ADC (Kaposi sarcoma, non-Hodgkin lymphoma) and NADC (lung, invasive anal, head/neck cancers, and Hodgkin lymphoma). RESULTS A total of 41,762 persons contributed 241,556 person-years (PY). A total of 1832 cancers were diagnosed [incidence rate: 0.76/100 PY (95% confidence interval: 0.72 to 0.79)], 718 ADC [0.30/100 PY (0.28-0.32)], and 1114 NADC [0.46/100 PY (0.43-0.49)]. Longer exposure to cART was associated with a lower ADC risk [adjusted rate ratio: 0.88/year (0.85-0.92)] but a higher NADC risk [1.02/year (1.00-1.03)]. Both PI and NNRTI use were associated with a lower ADC risk [PI: 0.96/year (0.92-1.00); NNRTI: 0.86/year (0.81-0.91)]. PI use was associated with a higher NADC risk [1.03/year (1.01-1.05)]. Although this was largely driven by an association with anal cancer [1.08/year (1.04-1.13)], the association remained after excluding anal cancers from the end point [1.02/year (1.01-1.04)]. No association was seen between NNRTI use and NADC [1.00/year (0.98-1.02)]. CONCLUSIONS Cumulative use of PIs may be associated with a higher risk of anal cancer and possibly other NADC. Further investigation of biological mechanisms is warranted.

Noninvasive Urinary Metabolomic Profiling Identifies Diagnostic and Prognostic Markers in Lung Cancer

Lung cancer remains the most common cause of cancer deaths worldwide, yet there is currently a lack of diagnostic noninvasive biomarkers that could guide treatment decisions. Small molecules (<1,500 Da) were measured in urine collected from 469 patients with lung cancer and 536 population controls using unbiased liquid chromatography/mass spectrometry. Clinical putative diagnostic and prognostic biomarkers were validated by quantitation and normalized to creatinine levels at two different time points and further confirmed in an independent sample set, which comprises 80 cases and 78 population controls, with similar demographic and clinical characteristics when compared with the training set. Creatine riboside (IUPAC name: 2-{2-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)-oxolan-2-yl]-1-methylcarbamimidamido}acetic acid), a novel molecule identified in this study, and N-acetylneuraminic acid (NANA) were each significantly (P < 0.00001) elevated in non-small cell lung cancer and associated with worse prognosis [HR = 1.81 (P = 0.0002), and 1.54 (P = 0.025), respectively]. Creatine riboside was the strongest classifier of lung cancer status in all and stage I-II cases, important for early detection, and also associated with worse prognosis in stage I-II lung cancer (HR = 1.71, P = 0.048). All measurements were highly reproducible with intraclass correlation coefficients ranging from 0.82 to 0.99. Both metabolites were significantly (P < 0.03) enriched in tumor tissue compared with adjacent nontumor tissue (N = 48), thus revealing their direct association with tumor metabolism. Creatine riboside and NANA may be robust urinary clinical metabolomic markers that are elevated in tumor tissue and associated with early lung cancer diagnosis and worse prognosis.

Predicting 5- and 10-year survival in older women with early-stage breast cancer: self-rated health and walking ability.

OBJECTIVES To determine life expectancy for older women with breast cancer. DESIGN Prospective longitudinal study with 10 years of follow-up data. SETTING Hospitals or collaborating tumor registries in four geographic regions (Los Angeles, California; Minnesota; North Carolina; Rhode Island). PARTICIPANTS Women aged 65 and older at time of breast cancer diagnosis with Stage I to IIIA disease with measures of self-rated health (SRH) and walking ability at baseline (N = 615; 17% aged ≥80, 52% Stage I, 58% with ≥2 comorbidities). MEASUREMENTS Baseline SRH, baseline self-reported walking ability, all-cause and breast cancer-specific estimated probability of 5- and 10-year survival. RESULTS At the time of breast cancer diagnosis, 39% of women reported poor SRH, and 28% reported limited ability to walk several blocks. The all-cause survival curves appear to separate after approximately 3 years, and the difference in survival probability between those with low SRH and limited walking ability and those with high SRH and no walking ability limitation was significant (0.708 vs 0.855 at 5 years, P ≤ .001; 0.300 vs 0.648 at 10 years, P < .001). There were no differences between the groups in breast cancer-specific survival at 5 and 10 years (P = .66 at 5 years, P = .16 at 10 years). CONCLUSION The combination of low SRH and limited ability to walk several blocks at diagnosis is an important predictor of worse all-cause survival at 5 and 10 years. These self-report measures easily assessed in clinical practice may be an effective strategy to improve treatment decision-making in older adults with cancer.

Cause-Specific Long-Term Mortality in Survivors of Childhood Cancer in Switzerland: A Population Based Study.

Survivors of childhood cancer have a higher mortality than the general population. We describe cause-specific long-term mortality in a population-based cohort of childhood cancer survivors. We included all children diagnosed with cancer in Switzerland (1976-2007) at age 0-14 years, who survived ≥5 years after diagnosis and followed survivors until December 31, 2012. We obtained causes of death (COD) from the Swiss mortality statistics and used data from the Swiss general population to calculate age-, calendar year- and sex-standardized mortality ratios (SMR), and absolute excess risks (AER) for different COD, by Poisson regression. We included 3'965 survivors and 49'704 person years at risk. Of these, 246 (6.2%) died, which was 11 times higher than expected (SMR 11.0). Mortality was particularly high for diseases of the respiratory (SMR 14.8) and circulatory system (SMR 12.7), and for second cancers (SMR 11.6). The pattern of cause-specific mortality differed by primary cancer diagnosis, and changed with time since diagnosis. In the first 10 years after 5-year survival, 78.9% of excess deaths were caused by recurrence of the original cancer (AER 46.1). Twenty-five years after diagnosis, only 36.5% (AER 9.1) were caused by recurrence, 21.3% by second cancers (AER 5.3) and 33.3% by circulatory diseases (AER 8.3). Our study confirms an elevated mortality in survivors of childhood cancer for at least 30 years after diagnosis with an increased proportion of deaths caused by late toxicities of the treatment. The results underline the importance of clinical follow-up continuing years after the end of treatment for childhood cancer. This article is protected by copyright. All rights reserved.

Primary lung cancer after breast cancer: The role of radiation therapy and cigarette smoking

The magnitude of the interaction between cigarette smoking, radiation therapy, and primary lung cancer after breast cancer remains unresolved. This case control study further examines the main and joint effects of cigarette smoking and radiation therapy (XRT) among breast cancer patients who subsequently developed primary lung cancer, at The University of Texas M. D. Anderson Cancer Center (MDACC) in Houston, Texas. Cases (n = 280) were women diagnosed with primary lung cancer between 1955 and 1970, between 30–89 years of age, who had a prior history of breast cancer, and were U.S. residents. Controls (n = 300) were randomly selected from 37,000 breast cancer patients at MDACC and frequency matched to cases on age at diagnosis (in 5-year strata), ethnicity, year of breast cancer diagnosis (in 5-year strata), and had survived at least as long as the time interval for lung cancer diagnosis in the cases. Stratified analysis and unconditional logistic regression modeling were used to calculate the main and joint effects of cigarette smoking and radiation treatment on lung cancer risk. Medical record review yielded smoking information on 93% of cases and 84% of controls, and among cases 45% received XRT versus 44% of controls. Smoking increased the odds of lung cancer in women who did not receive XRT (OR = 6.0, 95%CI, 3.5–10.1) whereas XRT was not associated with increased odds (OR = 0.5, 95%CI, 0.2–1.1) in women who did not smoke. Overall the odds ratio for both XRT and smoking together compared with neither exposure was 9.00 (9 5% CI, 5.1–15.9). Similarly, when stratifying on laterality of the lung cancer in relation to the breast cancer, and when the time interval between breast and lung cancers was >10 years, there was an increased odds for both smoking and XRT together for lung cancers on the same side as the breast cancer (ipsilateral) (OR = 11.5, 95% CI, 4.9–27.8) and lung cancers on the opposite side of the breast cancer (contralateral) (OR= 9.6, 95% CI, 2.9–0.9). After 20 years the odds for the ipsilateral lung were even more pronounced (OR = 19.2, 95% CI, 4.2–88.4) compared to the contralateral lung (OR = 2.6, 95% CI, 0.2–2.1). In conclusion, smoking was a significant independent risk factor for lung cancer after breast cancer. Moreover, a greater than multiplicative effect was observed with smoking and XRT combined being especially evident after 10 years for both the ipsilateral and contralateral lung and after 20 years for the ipsilateral lung. ^

The role of smoking status on postoperative complications and survival in lung cancer patients presenting to M.D. Anderson Cancer Center

It is estimated that 50% of all lung cancer patients continue to smoke after diagnosis. Many of these lung cancer patients who are current smokers often experience tremendous guilt and responsibility for their disease, and feel it might be too late for them to quit smoking. In addition, many oncologists may be heard to say that it is 'too late', 'it doesn't matter', 'it is too difficult', 'it is too stressful' for their patients to stop smoking, or they never identify the smoking status of the patient. Many oncologists feel unprepared to address smoking cessation as part of their clinical practice. In reality, physicians can have tremendous effects on motivating patients, particularly when patients are initially being diagnosed with cancer. More information is needed to convince patients to quit smoking and to encourage clinicians to assist patients with their smoking cessation. ^ In this current study, smoking status at time of lung cancer diagnosis was assessed to examine its impact on complications and survival, after exploring the reliability of smoking data that is self-reported. Logistic Regression was used to determine the risks of smoking prior to lung resection. In addition, survival analysis was performed to examine the impact of smoking on survival. ^ The reliability of how patients report their smoking status was high, but there was some discordance between current smokers and recent quitters. In addition, we found that cigarette pack-year history and duration of smoking cessation were directly related to the rate of a pulmonary complication. In regards to survival, we found that current smoking at time of lung cancer diagnosis was an independent predictor of early stage lung cancer. This evidence supports the idea that it is "never too late" for patients to quit smoking and health care providers should incorporate smoking status regularly into their clinical practice.^

Hormonal exposure and risk of pancreatic cancer in the United States

Background. In the United States, the incidence of pancreatic cancer has increased; more than 37,000 new cases of pancreatic cancer were diagnosed in the year 2007. Overall, the five-year survival rate is about 5% and pancreatic cancer ranks the fourth leading cause of cancer-related mortality among men and women. Despite the observed progress in cancer diagnosis and treatment, pancreatic cancer remains an unresolved significant public health problem in the United States. Familial pancreatic cancer has been confirmed to be responsible for approximately 10% of pancreatic cancer cases. However, 90% are still without known inherited predisposition. Until now, the role of oral contraceptive pills (OCPs) and hormonal replacement therapy (HRT) among women with pancreatic cancer remain unclear. We examined the association of exogenous hormonal uses in US women with risk of pancreatic cancer. ^ Methods. This was an active hospital-based case-control study which is conducted at the department of gastrointestinal medical oncology in The University of Texas M.D. Anderson Cancer Center. Between January 2005 and December 2007, a total of 287 women with pathologically confirmed pancreatic cancer (cases) and 287 healthy women (controls) were included in this investigation. Both cases and controls were frequency matched by age and race. Information about the use of hormonal contraceptives and hormonal replacement therapy (HRT) preparations as well as information about several risk factors of pancreatic cancer were collected by personal interview. Univariate and multivariate analyses were performed in this study to analyze the data. ^ Results. We found a statistical significant protective effect for use of exogenous hormone preparations on pancreatic cancer development (adjusted odds ratio [AOR], 0.4; 95% confidence interval [CI], 0.2–0.8). In addition, a 40% reduction in pancreatic cancer risk was observed among women who ever used any of the contraceptive methods including oral contraceptive pills (AOR, 6; 95% CI, 0.4–0.9). ^ Conclusions. Consistent with previous studies, the use of exogenous hormone preparations including oral contraceptive pills may confers a protective effect for pancreatic cancer development. More studies are warranted to explore for the underlying mechanism of such protection.^

Racial/ethnic differences in factors influencing screening and treatment among prostate cancer patients

Background. Racial/ethnic differences have been found in various aspects of cancer care. But a limited number of studies have examined the racial/ethnic differences in predictors of prostate-specific antigen (PSA) screening in a group of prostate cancer patients and have attempted to identify the racial/ethnic differences in treatment discussions, treatment choice and treatment received for organ-confined localized prostate cancer (PCa) among three major racial/ethnic groups of the USA. This study was conducted to redress this lack of information. ^ Methods. This study was conducted on a group of 935 prostate cancer patients representing all three major race/ethnic groups (Whites, African Americans and Hispanics) who were treated at various medical institutes of the Texas Medical Center, Houston between 1996 and 2004 to identify the racial/ethnic differences in predictors of PSA screening. A subset of 640 patients who had organ-confined localized prostate cancer was selected to examine the racial/ethnic differences in treatment discussions, treatment choice and treatment received for their localized prostate cancer. They were interviewed by trained research interviewers of MD Anderson Cancer Center using a validated structured questionnaire. ^ Results. The results showed that African American (54.4%) and Hispanic patients (42.3%) were significantly less likely (p=0.004 and p<.001, respectively) than White patients (63.2%) to report having had PSA screening before their prostate-cancer diagnosis. Among Whites, only education and annual check-ups predicted the use of PSA screening, whereas in African Americans two more additional factors, marital status and bode-mass index (BMI), significantly predicted PSA screening. Among Hispanics, like two other groups, education and annual check-ups also appeared as a significant predictor of PSA screening. ^ Results from multivariable logistic regression showed that African American patients were 15% less likely (OR=0.85, 95% CI=0.61-1.17, p=0.32) and Hispanics patients were 40% less likely (OR=0.60, 95% CI=0.41-0.87, p=0.008) to undergo PSA screening than Whites after adjusting for education and age at diagnosis for African Americans, and for education, annual check-ups and age at diagnosis for Hispanics. ^ This study revealed that health professionals were less likely to discuss surgery (79.9% vs. 93.2%) and watchful waiting (27.9% vs. 43.9%) with Hispanics compared to Whites. African Americans were more likely to choose (35.1% vs. 27.7%) and receive radiation therapy (38.3% vs.31.4%) than Whites. A comparison of concordance between treatment choice and treatment received showed that the highest concordance was found for watchful waiting and radiation therapy among African Americans (100% and 85.9%, respectively) whereas the highest concordance (96.9%) was found for surgery among Hispanics. ^ Conclusions. In this multiethnic study, the rates of PSA screening and its potential predictors varied by racial/ethnic groups. Substantial racial/ethnic variations were also found in treatment discussion, but the differences were not evident for treatment choice and treatment received. Health-education programs and culturally appropriate educational outreach efforts, especially targeted for high-risk groups, are needed to reduce these disparities. In the current climate of uncertainty about the benefits of PSA screening, or the benefit of one treatment over others, men should have access to information and services regardless of race/ethnicity so that they can make informed decisions. Further in-depth studies are needed in other settings to confirm these findings with the goal of developing an intervention to address these concerns. ^