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Keywords:

  • prostatic neoplasms;
  • urology;
  • Agent Orange;
  • risk factors;
  • veterans

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. FUNDING SOURCES
  8. CONFLICT OF INTEREST DISCLOSURES
  9. REFERENCES

BACKGROUND

Agent Orange (AO) exposure (AOe) is a potential risk factor for the development of prostate cancer (PCa). However, it is unknown whether AOe specifically increases the risk of lethal PCa. The objective of this study was to determine the association between AOe and the risk of detecting high-grade PCa (HGPCa) (Gleason score ≥7) on biopsy in a US Veteran cohort.

METHODS

Risk factors included clinicodemographic and laboratory data from veterans who were referred for an initial prostate biopsy. Outcomes were defined as the presence versus the absence of PCa, HGPCa, or low-grade PCa (LGPCa) (Gleason score ≤6) in biopsy specimens. Risk among AOe veterans relative to unexposed veterans was estimated using multivariate logistic regression. Separate models were used to determine whether AOe was associated with an increased risk of PCa, HGPCa, or LGPCa.

RESULTS

Of 2720 veterans who underwent biopsy, PCa was diagnosed in 896 veterans (32.9%), and 459 veterans (16.9%) had HGPCa. AOe was associated with a 52% increase in the overall risk of detecting PCa (adjusted odds ratio, 1.52; 95% confidence interval, 1.07-2.13). AOe did not confer an increase in the risk of LGPCa (adjusted odds ratio, 1.24; 95% confidence interval, 0.81-1.91), although a 75% increase in the risk of HGPCa was observed (adjusted odds ratio, 1.75; 95% confidence interval, 1.12-2.74). AOe was associated with a 2.1-fold increase (95% confidence interval, 1.22-3.62; P < .01) in the risk of detecting PCa with a Gleason score ≥8.

CONCLUSIONS

The current results indicated that an increased risk of PCa associated with AOe is driven by an increased risk of HGPCa in men who undergo an initial prostate biopsy. These findings may aid in improved PCa screening for Vietnam-era veterans. Cancer 2013;119:2399-2404. © 2013 American Cancer Society.


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. FUNDING SOURCES
  8. CONFLICT OF INTEREST DISCLOSURES
  9. REFERENCES

Prostate cancer (PCa) is the most commonly diagnosed visceral malignancy among men in the US and the second leading cause of male cancer-related deaths.[1] Although the treatment of clinically apparent cancer results in improved overall survival,[2] the effectiveness of routine PCa screening for the detection of subclinical disease remains an area of intense controversy. Two large population-based studies of routine PCa screening demonstrated a vast propensity for the detection of clinically insignificant cancer.[3, 4] It is noteworthy that no difference in overall survival between screened and nonscreened men was observed in 1 study, and only a modest improvement in survival was observed in the other. These findings recently led to a categorical recommendation against prostate-specific antigen (PSA)-based screening by the US Preventive Services Task Force.[5] The panel cited the need for improved biomarkers for the detection of clinically significant prostate cancer. However, because of limitations in the data, they were unable to assess the effectiveness of prostate screening in special populations, such as Vietnam War veterans exposed to Agent Orange (AO).

AO exposure (AOe) has been studied as a potential risk factor for the development of PCa. AO was a commercially manufactured defoliate that was sprayed extensively during the Vietnam War. Because of a side-product of chemical manufacturing, AO was contaminated with the toxin 2,3,7,8-tetrachlorodibenzo-p-dioxin, a putative carcinogen. Sufficient evidence has linked AOe to several other malignancies, including soft tissue sarcoma, Hodgkin disease, and non-Hodgkin lymphoma.[6] Limited but suggestive evidence exists for an association with respiratory cancers, PCa, and multiple myeloma.[6] Dioxins remain an area of important interest, because these environmental toxins continue to be produced through chemical processing and municipal waste incineration. These chemicals can then enter the food chain through soil contamination.[7]

Vietnam veterans are now reaching their mid-60s, the age at which new cases of PCa are most commonly diagnosed in the United States.[8] To more accurately assess the latent effects of AOe on PCa risk, a reassessment of contemporary biopsy data is needed. Roughly 8 million men in the United States are veterans of the Vietnam War.[9] On the basis of national PCa rates between 2005 and 2007, it is predicted that nearly 1.4 million of these men will develop PCa during their lifetime.[8] Although no real estimates exist for the percentage of Vietnam veterans who experienced AOe, roughly 3 million veterans served in Southeast Asia alone, where AO was used extensively in the combat theater. The primary objectives of this study were 1) to estimate the risk of PCa and high-grade PCa (HGPCa) in veterans with AOe relative to the risk for those without exposure, 2) to determine whether AOe is associated with a unique increase in HGPCa or whether there is an equal effect on the risk of low-grade PCa (LGPCa), and 3) to examine AOe by service branch to rule out potential confounding.

MATERIALS AND METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. FUNDING SOURCES
  8. CONFLICT OF INTEREST DISCLOSURES
  9. REFERENCES

Overview

Our study is an historic cohort analysis of 2720 veterans who were referred to the Portland Veterans Affairs Medical Center (PVAMC) and underwent an initial prostate biopsy. Any patient who had a prior diagnosis of prostate cancer was excluded from the database. Historic information regarding PCa risk factors and AOe were collected for each veteran. To assess possible risk factors for a positive prostate biopsy, clinical information for each patient, including AOe, was recorded using a standard data form before each prostate biopsy procedure and then collated with the prostate biopsy pathology results.

Data Management and Collection

Clinical, laboratory, biopsy parameters, and transrectal ultrasound (TRUS) data were recorded for all patients using a uniform template. Pathology reports were accessed to determine the presence of cancer and the biopsy grade (Gleason score). Patient information in this database was linked to historic information from the Veterans Integrated Service Network 20 Consumer Health Information Performance Sets Data Warehouse. Linking our prostate biopsy database to the data warehouse allowed us to capture additional clinical information, validate existing TRUS biopsy data, and obtain information on AOe.

The study principal investigator performed quality-assurance checks by comparing data against veterans' electronic medical records. Operating under a waiver of informed consent, all study procedures were conducted after receiving approval by the PVAMC Institutional Review Board and Research and Development Committee. For statistical analysis, the data, without personal identifiers, was exported into STATA statistical software (version 11.0: Stata Corporation, College Station, Tex).

Risk Factor Information

Data used in this analysis included AOe, family history of PCa, age, race, PSA, digital rectal examination (DRE), PSA density (PSAD) (PSA/prostate volume = PSAD), body mass index (BMI), and service branch history. For purposes of quality assurance, missing data and outlier data were reviewed before anonymizing the data to assure that appropriate variable definitions were applied. Service branch and PSAD information was recorded in an attempt to reduce the potential for residual and unmeasured confounding.

AOe status, as classified within the Veterans Affairs (VA) electronic medical record, was determined during patient enrollment into the VA hospital system. Each individual was defined as either “exposed” or “unexposed” in accordance with the PVAMC standards for documenting AOe. Individuals who did not have available AOe status were classified as unexposed. This assumption was deemed appropriate: It is probable that individuals who have reported exposure would have this information available in their medical records, because AOe is a known risk factor for many different conditions/diseases.[6] Of the 2720 veterans in the study, only 9 (0.3%) did not have explicitly declared information regarding AOe status and, thus, were characterized as not exposed. The exposure status for the remaining 2711 veterans was obtained directly from the Veterans Integrated Service Network 20 data warehouse. Information in the data warehouse classified veterans as exposed either if their location of military service corresponded with a location where AO was known to have been used or if, at the time of enrollment into the VA hospital system (before prostate biopsy), the veteran reported AOe.

Outcome Definitions

The primary outcomes of this study were the needle-biopsy detection of histologic PCa and clinically significant PCa, defined as PCa with a Gleason score ≥7. A secondary objective was the detection of Gleason score ≥8 disease. The outcome for the first multivariate model (Model 1) was defined as positive versus negative cancer in the biopsy specimen. The outcome for Model 2 was defined as the detection of HGPCa (Gleason score ≥7) versus no HGPCa (low-grade cancer [Gleason score ≤6] or no PCa). To determine whether AOe was associated with an increased risk of either LGPCa or HGPCa, 2 additional models (Models 3 and 4) were built. For Model 3, the outcomes were HGPCa versus no PCa. For Model 4, the outcomes were LGPCa versus no PCa. A final model (Model 5) examined the association between AOe and Gleason score ≥8 PCa.

Statistical Analysis

Separate multiple logistic regression models were built using STATA 11.0 to accomplish the primary objectives of this study. The models were assessed for goodness of fit, and the area under the receiver operating characteristic curve was used as a measure of the model's overall accuracy as well as to determine the cutoff point for the predictive probability of a positive biopsy.

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. FUNDING SOURCES
  8. CONFLICT OF INTEREST DISCLOSURES
  9. REFERENCES

Population Demographics

The study population included 93.6% white men, 3.8% black men, 1% Hispanic men, and <1% Asian and Native American men. No significant association was observed between race and the PCa outcome variables or AOe. The average age (±standard deviation) for all veterans who were referred for prostate biopsy was 64.7 ± 7.4 years. The average age of individuals who had PCa identified on biopsy was 65.7 years compared with 64.2 years for those without PCa (P < .0001), as indicated in Table 1.

Table 1. Study Population Demographics Overall and by Prostate Biopsy/Cancer Grade
 Mean (95% CI)Mean (95% CI)Mean (95% CI)
VariableTotal Study PopulationPositive Prostate Biopsy, n = 896Negative Prostate Biopsy, n = 1824PaHGPCa, n = 459LGPCa/No PCa, n = 2261Pa
  1. Abbreviations: AO, Agent Orange; BMI, body mass index; CI, confidence interval; HGPCa, high-grade prostate cancer (Gleason score ≥7); LGPCa, low-grade prostate cancer (Gleason score ≤6); PCa, prostate cancer; PSA, prostate-specific antigen; PSAD, prostate-specific antigen density.

  2. a

    P values for means were calculated using 2-sample t tests with equal variances; P values for proportions were calculated using Pearson chi-square tests.

  3. b

    Excluding extreme values (>1000 ng/mL).

  4. c

    Excluding extreme values (>20 ng/mL/mL).

AO exposure, %7.46 (6.48-8.45)8.3 (6.5-10.1)7.1 (5.9-8.2).2688.7 (6.1-11.3)7.2 (6.1-8.3).263
Age at biopsy, y64.7 (64.4-65)65.7 (65.2-66.2)64.2 (63.9-64.6)< .000166.5 (65.8-67.2)64.4 (64.1-64.7)< .0001
BMI, kg/m229.3 (29.1-29.6)29.2 (29.3-30.2)29.1 (28.8-29.5)< .0529.7 (29.1-30.3)29.2 (29.2-29.5).186
PSA, ng/mLb9.15 (8.06-10.2)12.1 (9.3-15)7.7 (6.8-8.5)< .00136.4 (15.4-57.4)7.5 (6.8-8.2)< .001
PSAD, ng/mL/mLc0.19 (0.18-0.21)0.32 (0.12-0.14)0.13 (0.12-0.14)< .00010.43 (0.34-0.51)0.15 (0.14-0.16)< .0001
Family history, %18.6 (17.1-20)21.4 (18.8-24.1)17.2 (15.4-18.9).00722 (18.2-25.8)17.9 (16.3-19.4).038

Information on BMI was available for 61.8% (n = 1681) of the study population. Of these, <1% of men were categorized as underweight (BMI <18.5 kg/m2), 17.4% were normal weight (BMI 18.5-24.9 kg/m2), 39.4% were overweight (BMI 25.0-29.9 kg/m2), and 42.3% were obese (BMI >30 kg/m2). Table 1 indicates that no difference was observed between the BMI of veterans with and without PCa. There was also no difference in BMI category between AOe and non-AOe veterans (see Table 2).

Table 2. Study Population Demographics by Agent Orange Exposure Status
 Entire Study PopulationIndividuals With Positive Prostate BiopsyIndividuals With HGPCa
 Mean (95% CI) Mean (95% CI) Mean (95% CI) 
VariableAO Exposure, n = 203No Exposure, n = 2517PaAO Exposure, n = 74No Exposure, n = 822PaAO Exposure, n = 40No Exposure, n = 419Pa
  1. Abbreviations: AO, Agent Orange; BMI, body mass index; CI, confidence interval; HGPCa, high-grade prostate cancer (Gleason score ≥7); NA, not applicable; PSA, prostate-specific antigen; PSAD, prostate-specific antigen density.

  2. a

    P values for means were calculated using 2-sample t tests with equal variances; P values for proportions were calculated using Pearson chi-square tests.

  3. b

    Excluding extreme values (>5000 ng/mL).

  4. c

    Excluding extreme values (>20 ng/mL/mL).

Age at biopsy, y60.6 (60.0-61.2)65.0 (64.8-65.3)< .000161.4 (60.5-62.3)66.1 (65.6-66.6)< .000162.1 (60.9-63.3)66.9 (66.1-67.6)< .001
BMI, kg/m230.0 (29.2-30.8)29.3 (29.0-29.6).11730.1 (28.8-31.4)29.7 (29.2-30.2).55029.3 (27.6-31.1)29.7 (29.1-30.4).686
PSA, ng/mLb11.2 (4.3-18.2)12.4 (8.6-16.2).8648.8 (6.1-11.5)23.0 (11.3-34.7).4787.9 (7.6-8.1)7.7 (7.6-7.8).357
PSAD, ng/mL/mLc0.20 (0.13-0.28)0.19 (0.18-0.21).7100.34 (0.14-0.53)0.32 (0.27-0.37).8450.30 (0.17-0.42)0.44 (0.35-0.53).344
Family history, %20.2 (14.7-25.7)18.4 (16.9-19.9).53425.7 (15.7-35.6)21 (18.3-23.8).35332.5 (18-47)21 (17.1-24.9).094
Positive biopsy, %36.5 (29.8-43.1)32.7 (30.8-34.5).268100100NA100100NA

Of the veterans without PCa, 17.2% reported a family history of PCa compared with 21.4% of veterans with PCa (P = .007) (Table 1). No association was observed between PCa family history and history of AOe (Table 2). Finally, PCa was detected in 896 of the 2720 veterans (32.9%) who were referred for prostate biopsy. Of those 896 men with PCa, 459 (16.9%) had HGPCa (Gleason score ≥7).

Agent Orange Exposure

Of the 2720 veterans who underwent a prostate biopsy procedure, 203 (7.5%) met the definition for AOe as reflected in their medical records. In multivariate logistic regression analysis (for the all models of analyses, see Table 3), the primary predictor of interest, AOe, was associated significantly with an increased risk of a positive prostate biopsy (Model 1). The risk of PCa in those with AOe was 52% greater (adjusted odds ratio, 1.52; 95% confidence interval, 1.07-2.13; P = .017) than the risk of PCa in those without AOe. Additional independent predictors of PCa included a positive family history, increased age, Marine Corps service, increased PSAD, and abnormal DRE results.

Table 3. Comparison of Effects Observed in Separate Multivariate Regression Analyses
 Model 1: All PCA (LGPCa & HGPCa) vs No PCaModel 2: HGPCa vs Other (LGPCa and No PCa)Model 3: HGPCa vs No PCaModel 4: LGPCa vs No PCaModel 5: Gleason ≥8 vs Other
VariableOR95% CIPaOR95% CIPaOR95% CIPaOR95% CIPaOR95% CIPa
  1. Abbreviations: CI, confidence interval; DRE, digital rectal examination; HGPCa, high-grade prostate cancer (Gleason score ≥7); LGPCa, low-grade prostate cancer (Gleason score ≤6); OR, odds ratio; PCa, prostate cancer; PSAD, prostate-specific antigen density.

  2. a

    P values were calculated using the Wald test.

  3. bThis was the primary predictor.

AO exposure1.521.07-2.13.0171.741.14-2.63.0101.751.12-2.74.0141.240.81-1.91.3242.101.22-3.61< .01
Age, y               
<601.001.001.001.001.00
60-691.391.10-1.75.0051.511.11-2.05.0091.571.13-2.18.0071.270.96-1.68.0921.781.15-2.77.01
≥701.541.19-2.00.0011.811.29-2.53.0011.921.34-2.75< .0011.250.91-1.72.1681.570.97-2.55.07
PSAD, ng/mL/mL               
<0.101.001.001.001.001.00
0.10-0.142.091.61-2.72< .0012.031.34-3.06.0012.301.51-3.48< .0012.041.49-2.79< .0012.131.07-4.27.03
0.15-0.194.073.06-5.42< .0014.963.31-7.45< .0016.204.08-9.41< .0013.162.22-4.50< .0014.642.37-9.05< .001
≥0.208.856.88-11.4< .00110.07.05-12.3< .00114.710.1-21.1< .0016.204.57-8.42< .00112.87.19-22.7< .001
DRE               
Normal1.001.001.001.001.00
Suspicious1.801.48-2.18< .0011.881.46-2.41< .0012.141.64-2.79< .0011.631.29-2.07< .0011.601.60-3.38< .001
Cancer likely10.36.63-17.0< .00112.88.72-18.9< .00119.111.8-30.9< .0014.552.55-8.14< .00111.411.4-26.6< .001

In Model 2, which compared the presence versus the absence of HGPCa, veterans who had AOe had a 74% greater risk of HGPCa compared with those who did not have AOe (adjusted odds ratio, 1.74; 95% confidence interval, 1.14-2.63; P = .01). AOe was associated predominantly with HGPCa (adjusted odds ratio, 1.75; 95% confidence interval, 1.12-2.74) versus no PCa in Model 3. In Model 4, no significant association was observed in the analysis of LGPCa versus no PCa (adjusted odds ratio, 1.24; 95% confidence interval, 0.81-1.91). Model 5 demonstrated an even stronger association between AOe and the detection of PCa with a Gleason score ≥8 (adjusted odds ratio, 2.1; 95% confidence interval, 1.22-3.62; P < .01). Additional predictors of HGPCa included increased age, service branch, increased PSAD, and abnormal DRE results. However, our multivariate models only included significant confounders (age, DRE results, and PSAD), because adjustment for the remaining variables had a less than 10% effect on the association between AOe and HGPCa.

Veterans with AOe also presented with abnormal prostate screening parameters and underwent a prostate biopsy roughly 5 years earlier than veterans without AOe (Table 2). Among those with PCa, veterans who had AOe were diagnosed, on average, roughly 5 years earlier than veterans who did not have AOe (mean age at PCa diagnosis: AOe group, 61.4 years; nonexposed group, 66.1 years; P < .0001 for the difference). Similar age-range results were observed when we compared age at diagnosis according to AOe status among individuals with HGPCa (mean age at HGPCa diagnosis of HGPCa: AOe group, 62.1 years; nonexposed group, 66.9 years; P < .001 for the difference). Although this result suggests that age potentially modifies the effect of AOe on the risk of PCa and HGPCa, the interaction was not identified as significant (P = .119) in the multivariate models.

Reported percentages of AOe in each branch of the military and referral for prostate biopsy were as follows: Army, 8.9%; Navy, 4.2%; Air Force, 6.3%; Marine Corps, 14.3%; Coast Guard, 0%; Merchant Marines, 0%; and 3.9% in the unknown group. The frequency of positive biopsy in AOe veterans was compared over different service branches. Air Force veterans were used as the reference category, because this service branch did the majority of AO spraying during the Vietnam War and has received the most attention from research about AOe veterans. This allowed us to compare the frequency of positive biopsy and HGPCa between the AOe Airmen who were responsible for spraying AO versus Marine and Army ground troops. Upon crude comparison, no significant associations between service branch and the frequency of PCa in AOe veterans were observed.

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. FUNDING SOURCES
  8. CONFLICT OF INTEREST DISCLOSURES
  9. REFERENCES

Clinically accessible biomarkers are needed to refine current PCa screening practices. Optimizing the detection of potentially lethal PCa is likely to result in an improvement in PCa survival and treatment-induced morbidity. The US Preventive Services Task Force guideline panel has recently recommended against population-based PSA screening[5]; however, it is important to note that the effect of AOe was not addressed by the task force. Our results demonstrate that AOe is positively associated with a 52% increase in the risk of PCa detection at initial prostate biopsy. Other recent studies also suggest that AOe increases the risk of PCa.[10, 11] Of chief concern is our finding that AOe was associated with a 75% increase in the risk of PCa with a Gleason score ≥7 and a 110% increase in the risk of PCa with a Gleason score ≥8 among veterans who are referred for an initial prostate biopsy. AOe appears to have a unique effect on the risk of HGPCa and a weak but nonsignificant increase in the risk of LGPCa. This strongly suggests that aggressive PCa primarily is driving the observed increase in overall PCa risk. Thus, AOe may be a readily identifiable clinical biomarker for the prediction of lethal PCa and would likely increase the sensitivity for detecting cancers in the veteran population that are more likely to be aggressive and potentially lethal without adding to the problem of the overdiagnosis of low-risk cancers.

In the current study, we observed that the veterans with AOe who were at risk for having HGPCa detected presented with abnormal prostate screen findings and, on average, had cancers detected 4 to 5 years earlier than nonexposed veterans. This observation is consistent with the study by Chamie et al, who reported an association between AOe and HGPCa among 363 men with prostate cancer in a population-based study of US Veterans. These findings may have significant implications in the development of effective PCa screening strategies for AOe veterans, because they may develop more life-threatening cancers earlier in their lives than non-AOe veterans or men in the general US population.

The effect of AOe on the risk of PCa detection has been an area of some scientific debate. Early studies failed to demonstrate a significant association between AOe and PCa detection[12, 13]; however, the majority of studies, including larger, more recent studies, have demonstrated a positive association between AOe and PCa.[10] The small sample sizes in the studies that reported positive but statistically nonsignificant associations warrant caution, because a type II error may account for these nonsignificant findings, in that those studies were not powered to identify an association with the strength we observed in our current study.

Limitations in our methodology should be considered. First, selection bias may have occurred if physicians were more likely to refer a patient for prostate biopsy if the physician knew a veteran had AOe. Not only would this create an inflation of the effect measure, but it also may account for AOe veterans' diagnoses at a younger average age than those without exposure. However, if differential selection bias occurred, then AOe veterans with similar PSA levels, DRE results, age, race, and family histories would be referred for prostate biopsy at a higher rate than similar nonexposed veterans. Thus, we would expect to observe a higher proportion of AOe veterans with no PCa or with LGPCa, because men with HGPCa generally display clinical symptoms, significantly elevated PSA, or abnormal DRE results, which would have caused them to be referred regardless of their AOe status. In our current study, the finding that AOe was associated significantly with a 75% increase in the risk of HGPCa is not consistent with this selection bias by physician referral. In addition, study physicians declined to take AOe into account at the time of prostate biopsy referral.

In the study by Chamie et al, the authors suggested the possibility that AOe may have been associated with an increase in PSA, which may have lead to veterans with AOe being referred for a prostate biopsy. In our study, AOe veterans had a mean maximum PSA of 11.2 ng/mL compared with 12.4 ng/mL in unexposed veterans. Of the veterans who had PCa diagnosed on biopsy, the average PSA of veterans in the AOe group was 8.8 ng/mL compared with 23.0 ng/mL in the nonexposed group. Neither difference was statistically significant; however, these findings suggest that AOe is not associated with a higher PSA level and is an independent predictor of both PCa and HGPCa on biopsy.

An additional consideration in our study was whether individuals changed their AOe status with the VA hospital after being diagnosed with PCa. If a large number of individuals switched exposure status after a positive prostate biopsy, then this would create a differential bias away from the null. In the study by Chamie et al, only 7 of 6214 men (0.11%) with AOe switched their exposure status after a diagnosis of cancer. Given the similar populations in our studies, we can assume that a similar proportion of veterans changed their exposure status. Thus, among our 203 AOe veterans, we expect that, at most, 1 veteran switched exposure status after his PCa diagnosis. If the proportion of veterans switching their exposure status in our study was 25 times the proportion in the study by Chamie et al, then only 5 or 6 veterans in our study made this switch. Thus, a change in AOe status cannot account for the observed association with HGPCa.

In conclusion, biomarkers for the prediction of life-threatening disease are needed to improve current PCa screening strategies. In our study, a history of AOe was associated with a 75% increase in the risk of life-threatening PCa, but it was not associated significantly with an increase in LGPCa. Incorporating AOe history into decision-making for PCa screening among veterans may help to better predict clinically significant PCa while not adding to the number of clinically insignificant PCa diagnoses.

FUNDING SOURCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. FUNDING SOURCES
  8. CONFLICT OF INTEREST DISCLOSURES
  9. REFERENCES

This material is a result of work supported with resources and the use of facilities at the Portland Veterans Affairs Medical Center.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. FUNDING SOURCES
  8. CONFLICT OF INTEREST DISCLOSURES
  9. REFERENCES
  • 1
    US Cancer Statistics Working Group. United States Cancer Statistics: 1999-2005 Incidence and Mortality Web-Based Report. Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention, National Cancer Institute; 2009.
  • 2
    Bill-Axelsson A, Holberg L, Ruutu M, et al. Scandinavian Prostate Cancer Group Study No 4. Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med. 2005;352:1977-1984.
  • 3
    Andriole GL, Crawford ED, Grubb RL 3rd, et al. PLCO Project Team. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med. 2009;360:1310-1319.
  • 4
    Schroder FH, Hugosson J, Roobol MJ, et al. ERSPC Investigators. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med. 2009;360:1320-1328.
  • 5
    Moyer VA. Screening for prostate cancer: US Preventive Services Task Force recommendation statement. Ann Intern Med. 2012;157:1-16.
  • 6
    Institute of Medicine. Veterans and Agent Orange: Update 2008. Washington, DC: The National Academies Press; 2009.
  • 7
    National Institute of Environmental Health Sciences. Dioxins: Fact Sheets. Research Triangle Park, NC: National Institutes of Environmental Health Sciences; 2012.
  • 8
    Altekruse SF, Kosary CL, Krapcho M, et al. eds. SEER Cancer Statistics Review, 1975-2007. Bethesda, MD: National Cancer Institute; 2009.
  • 9
    US Department of Veterans Affairs. Table 1I: veterans by state, age group, period, gender, 2000-2036. In: Vetpop 2007 State Tables. Washington, DC: US Department of Veterans Affairs; 2009. Available at: http//:www1.va.gov.vetdata/docs/VP2007_state.htm. [Accessed July 10, 2012.]
  • 10
    Akhtar FZ, Garabrant DH, Ketchum NS, Michaelk JE. Cancer in US Air Force veterans of the Vietnam War. J Occup Environ Med. 2004;46:123-136.
  • 11
    Chamie K, DeVere White RW, Lee D, Ok JH, Ellison LM. Agent Orange exposure, Vietnam War veterans, and the risk of prostate cancer. Cancer. 2008;113:2464-2470.
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    Giri VN, Cassidy AE, Beebe-Dimmer J, et al. Association between Agent Orange and prostate cancer: a pilot case-control study. Urology. 2004;63:757-760.
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    Zafar MB, Terris MK. Prostate cancer detection in veterans with a history of Agent Orange exposure. J Urol. 2001;166:100-103.