Skip to main content
  • AACR Publications
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

  • Register
  • Log in
Advertisement

Main menu

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • CEBP Focus Archive
    • Meeting Abstracts
  • For Authors
    • Call for Papers
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • OnlineFirst
    • Editors' Picks
    • Citation
    • Author/Keyword
  • News
    • Cancer Discovery News
  • AACR Publications
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

User menu

  • Register
  • Log in

Search

  • Advanced search
Cancer Epidemiology, Biomarkers & Prevention
Cancer Epidemiology, Biomarkers & Prevention

Advanced Search

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • CEBP Focus Archive
    • Meeting Abstracts
  • For Authors
    • Call for Papers
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • OnlineFirst
    • Editors' Picks
    • Citation
    • Author/Keyword
  • News
    • Cancer Discovery News
Null Results in Brief

Inherited Variations in AR, ESR1, and ESR2 Genes Are Not Associated With Prostate Cancer Aggressiveness or With Efficacy of Androgen Deprivation Therapy

Tong Sun, Gwo-Shu Mary Lee, Lillian Werner, Mark Pomerantz, William K. Oh, Philip W. Kantoff and Matthew L. Freedman
Tong Sun
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gwo-Shu Mary Lee
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lillian Werner
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mark Pomerantz
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
William K. Oh
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Philip W. Kantoff
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Matthew L. Freedman
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI: 10.1158/1055-9965.EPI-10-0216 Published July 2010
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Abstract

Background: Sex steroid hormone receptors mediate essential processes in normal prostate growth and contribute to prostate cancer development.

Method: In this study, we investigated the association between common inherited variation of the AR, ESR1, and ESR2 genes and two clinically relevant traits: the risk of developing aggressive prostate cancer and the response to androgen deprivation therapy (ADT) in a hospital-based cohort. A total of 43 tagging single nucleotide polymorphisms covering the loci of AR (n = 4), ESR1 (n = 32), and ESR2 (n = 7) were successfully genotyped in 4,073 prostate cancer cases.

Results: None of these single nucleotide polymorphisms were significantly associated with disease aggressiveness as assessed by the D'Amico risk classification, pathologic stage, or the response to ADT.

Conclusions: Our results suggest that common genetic variations in AR, ESR1, or ESR2 are not strongly associated with prostate cancer aggressiveness or response to ADT.

Impact: Our study did not find convincing evidence of inherited variations in the major receptors for androgens and estrogens and their associations with prostate cancer traits. Cancer Epidemiol Biomarkers Prev; 19(7); 1871–8. ©2010 AACR.

Introduction

Prostate cancer accounts for one fourth of all cancer diagnosed in men in the United States every year (1). Although most men will have an indolent form of the disease, aggressive prostate cancer is one of the major causes of death among men in developed countries (2). Androgen deprivation therapy (ADT) is the most commonly used treatment for advanced prostate cancer (3). Despite frequent responses, the majority of metastatic tumors will progress to castration-resistant prostate cancer, which is typically lethal (4). Therefore, it is important to understand the mechanisms involved in the development of aggressive prostate cancer and the progression to castration-resistant disease.

Sex steroid hormones, such as androgens and estrogens, are essential in normal prostate growth and carcinogenesis (5, 6). Accumulating evidence indicates that androgens, estrogens, and their corresponding receptors play crucial roles in prostate cancer development and progression (7, 8). Aberrant expression or mutations of hormone receptors in tumors are also found to be associated with prostate cancer aggressiveness and the development of resistance to ADT (9, 10). Recently, molecular epidemiologic studies have been conducted to evaluate the association of genetic polymorphisms in androgen receptor (AR), estrogen receptor α (ESR1), and estrogen receptor β (ESR2) with prostate cancer risk (11-16), but the results are inconclusive.

To investigate whether inherited variation in AR, ESR1, and ESR2 loci contribute to prostate cancer aggressiveness or the response to ADT, we systematically evaluated the AR, ESR1, and ESR2 loci in a large hospital-based prostate cancer patient cohort.

Materials and Methods

Study population

Details of the Dana-Farber Harvard Cancer Center SPORE (Gelb Center) Prostate Cancer Clinical Research Information System (CRIS) at the Dana-Farber Cancer Institute (DFCI) have been previously described (17). Briefly, the CRIS system consists of data-entry software, a central data repository, collection of patient data including comprehensive follow-up of all patients, and tightly integrated security measures. All patients seen at DFCI and Brigham and Women's Hospital with a diagnosis of prostate cancer are approached to participate. The consent rate for patients is 86%. The Institute Review Board approved this study specifically.

A total of 4,073 prostate cancer patients diagnosed from 1976 to 2007, who had consented during the period from 1993 to 2007 to provide information and tissue and had blood collected for research purposes, were included in this study cohort (18). To control the quality of the ethnicity information from the self-reported data, we sampled 3% of self-reported Caucasians (n = 180) and performed genotyping using 26 single nucleotide polymorphisms (SNP) that distinguish the Caucasian population from non-Caucasian populations (19). The genotyping data showed that none of the tested samples were in discordance, confirming the reliability of self-reported Caucasian ethnicity. For all individuals who ambiguously reported their ethnicity, including those reported as “American,” or those who did not report ethnicity information, their ethnicity was determined by genotyping using the same set of 26 SNPs. Only reliably self-reported or genotyping-confirmed Caucasians were eligible for this study. Age at diagnosis was calculated from the date of the first positive biopsy. Using the D'Amico risk classification criteria, prostate cancer patients were classified as low, intermediate, or high risk of clinical recurrence after primary therapy (20). Briefly, three risk groups were established based on serum prostate-specific antigen (PSA) level, biopsy Gleason score, and American Joint Commission on Cancer (AJCC) clinical tumor category at diagnosis. Low-risk patients had a PSA of 10 ng/mL, a Gleason score of ≤6, and tumor category T1c or T2a. Intermediate-risk patients had a PSA of 10.1 to 20 ng/mL or Gleason score of 7 or tumor category T2b. High-risk patients had a PSA of >20 ng/mL or Gleason score of 8 or tumor category T2c. Because original D'Amico risk classification was set to predict biochemical outcome of localized patients, in this study, patients who diagnosed with N1 or M1 diseases were regarded as high D'Amico risk class. Within the entire cohort, 1,716 of 4,073 patients were known to have undergone radical prostatectomy as the primary treatment. Pathologic stage was acquired by reviewing pathology reports. A subset of 553 patients out of the entire cohort belonged to the previously described ADT cohort for evaluating ADT efficacy (21, 22). Briefly, the ADT cohort included patients who received orchiectomy or Luteinizing-hormone-releasing hormone (LHRH) with or without an antiandrogen for nonlocalized, hormone-sensitive prostate cancer.

SNP selection and genotyping

The approach for tagging SNP selection was as previously described (23). To select SNPs for AR, ESR1, and ESR2, phase II data of Utah residents with Northern and Western European ancestry (CEU) population from the International HapMap project were used. The tagging SNPs were selected by pairwise algorithm implemented in the Haploview 4.1 program (24) to capture the unmeasured variants r2 > 0.8. In total, we selected 6 SNPs in AR, 35 SNPs in ESR1, and 7 SNPs in ESR2, which could capture common variation among the CEU population of each locus. The genotyping was done using with Sequenom iPLEX matrix-assisted laser desorption/ionization–time of flight mass spectrometry technology. Genotyping of one selected tagging SNP in AR (rs5919393) and three SNPs in ESR1 (rs12154178, rs3020325, and rs9340931) failed. Another SNP in AR, rs5031002, was excluded from further analysis due to its low frequency in the studied population (minor allele frequency = 0.023). Average genotyping success for all other SNPs was 97.9% (range, 92.7-99.8%). The concordance rate between duplicated samples (n = 255) was 99.96%.

Statistical analysis

Observed genotype distributions were tested for departure from Hardy-Weinberg equilibrium using Pearson's goodness-of-fit test. No SNP violated Hardy-Weinberg equilibrium (all P values > 0.05). The homozygous genotypes of frequencies <5% were combined with their corresponding heterozygous genotype for analysis. To investigate the association of genotypes with early-onset prostate cancer (≤60 years), and with prostate cancer aggressiveness following D'Amico risk classes of patients as previously noted (intermediate/high versus low), we estimated odds ratios and their 95% confidence intervals using unconditional logistic regression. We also examined the association between SNPs and radical prostatectomy pathologic stage (advanced, defined as pathologic T3-T4 or N1 or M1 versus localized T1-T2) with unconditional logistic regression in a subcohort with patients who underwent radical prostatectomy. The above analyses, with the exception of those for early-onset prostate cancer, were adjusted for age at diagnosis. In the ADT subcohort, median time to progression on ADT by genotype was estimated using Kaplan-Meier methods. Global association of genotypes with time to progression on ADT were assessed using log rank tests, and hazard ratios and 95% confidence intervals were estimated using Cox proportional hazard regression. The models for ADT subcohort analysis were not adjusted for age. All statistical analyses were done using version SAS version 9.1 (SAS Institute Inc.). A P value that remains <0.05 after 1,000 times permutation testing would be considered as statistically significant in entire cohort or radical prostatectomy subcohort analyses.

Results

Table 1 shows the patient characteristics of the entire cohort. The cohort includes 4,073 Caucasian prostate cancer patients. The mean age at diagnosis was 61.3 years (range, 42-91 years). Among 3,750 patients with biopsy Gleason score information, 1,771 (47%) had biopsy Gleason scores <7, 1,272 (34%) had Gleason scores of 7, and 707 (19%) had Gleason scores >7. A total of 3,056 patients had AJCC clinical stage information; among them, 92% (n = 2807) presented at diagnosis with T1 or T2 disease, 2% (n = 65) had T3 or T4 disease, and 6% (n = 184) were diagnosed with metastatic disease (N1 or M1). A total of 3,518 patients had PSA levels at diagnosis, with a median PSA of 6 ng/mL (Q1, Q3; 5, 11 ng/mL). Sufficient information for modified criteria of D'Amico risk classification was available for 3,347 patients, of whom 1,004 (30%) were low risk, 1,357 (40%) intermediate risk, and 986 (30%) high risk. A total of 1,716 patients underwent radical prostatectomy, of whom 1,161 (68%) had organ-confined (T1 or T2) disease at the time of receiving surgery, whereas 475 (28%) had extraprostatic tumors (T3 or T4) and 80 (4%) had metastatic tumors (N1 or M1). The pathologic Gleason score was <7 in 652 (39%), 7 in 769 (45%), and ≥7 in 1,040 (16%) patients. The characteristics of the ADT subcohort were as previously described (21, 22).

View this table:
  • View inline
  • View popup
Table 1.

Clinical characteristics of study cohort

Forty-three SNPs across the AR, ESR1, and ESR2 genes were successfully genotyped in this cohort. Table 2 shows the results for the association between these variants and age at diagnosis, disease aggressiveness, and response to ADT. We did not observe convincing significant associations of these SNPs with any of the traits. Although some SNPs (rs1204038 of AR, and rs2077647, rs532010, rs17081749, rs6902771, and rs3936674 of ESR1) showed nominally significant associations with early-onset or advanced-stage prostate cancer, considering the number of tests done, it is likely that these nominally significant results were due to chance. For example, none of them remained P < 0.05 after the adjustment for multiple comparisons, such as permutation testing.

View this table:
  • View inline
  • View popup
Table 2.

Gene locations and association with prostate cancer aggressiveness and efficiency of androgen deprivation therapy

Discussion

This was a large hospital-based study involving 4,073 cases that examined the association of inherited variation in AR, ESR1, and ESR2 with clinically relevant traits: age at diagnosis, prostate cancer aggressiveness, and the efficacy of ADT. No strong associations were observed. The strengths of our study include large sample size, detailed clinical information, and comprehensive evaluation of common genetic variation.

A prior study reported that an AR promoter SNP, rs17302090, was modestly significantly associated with an increased risk of prostate cancer death (25). The study also reported that this finding was more pronounced in patients who received ADT as primary treatment at diagnosis. However, we did not identify any associations between rs1204038, which is in strong linkage disequilibrium with rs17302090 (D' = 1.00, r2 = 0.80), and prostate cancer aggressiveness or ADT efficacy.

Hormonal status is clearly an important factor in prostate cancer biology. To date, however, there has been little evidence supporting the influence of common genetic variation on various prostate cancer–related traits. In our study, we did not find convincing evidence of inherited variations in the major receptors for androgens and estrogens and their associations with prostate cancer traits. There are several possible reasons for the lack of associations. First, aberrant expression, mutation, or splice variants of hormone receptors are frequently found mechanisms in prostate cancer progress and castration-resistance development. These somatic alterations may play a larger role than the influence of low-penetrant genetic variants for these traits. Second, other genes besides hormonal receptors in the steroidogenic and metabolic pathways are also important for prostate development and antiandrogen therapy response. Inherited variants in sex hormonal receptor genes perhaps interact with other variants in these pathways and play roles cooperatively. Last but not least, the current research strategy allows us to explore the role of common genetic variation; rare variants in these (or other) genes may be important in disease progression and response to the treatment.

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

Grant Support: SPORE in Prostate Cancer 2 P50 CA090381-06 and a Prostate Cancer Foundation Challenge Grant.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Footnotes

    • Received February 26, 2010.
    • Revision received March 19, 2010.
    • Accepted April 16, 2010.

    References

    1. ↵
      1. Jemal A,
      2. Siegel R,
      3. Ward E,
      4. Hao Y,
      5. Xu J,
      6. Thun MJ
      . Cancer statistics, 2009. CA Cancer J Clin 2009;59:225–49.
      OpenUrlCrossRefPubMed
    2. ↵
      1. Andriole GL,
      2. Crawford ED,
      3. Grubb RL III,
      4. et al
      . Mortality results from a randomized prostate-cancer screening trial. N Engl J Med 2009;360:1310–9.
      OpenUrlCrossRefPubMed
    3. ↵
      1. Pronzato P,
      2. Rondini M
      . Hormonotherapy of advanced prostate cancer. Ann Oncol 2005;4:iv80–4.
      OpenUrl
    4. ↵
      1. Singer EA,
      2. Golijanin DJ,
      3. Miyamoto H,
      4. Messing EM
      . Androgen deprivation therapy for prostate cancer. Expert Opin Pharmacother 2008;9:211–28.
      OpenUrlCrossRefPubMed
    5. ↵
      1. Ekman P
      . The prostate as an endocrine organ: androgens and estrogens. Prostate Suppl 2000;10:14–8.
      OpenUrlPubMed
    6. ↵
      1. Ricke WA,
      2. Wang Y,
      3. Cunha GR
      . Steroid hormones and carcinogenesis of the prostate: the role of estrogens. Differentiation 2007;75:871–82.
      OpenUrlCrossRefPubMed
    7. ↵
      1. Huang H,
      2. Tindall DJ
      . The role of the androgen receptor in prostate cancer. Crit Rev Eukaryot Gene Expr 2002;12:193–207.
      OpenUrlCrossRefPubMed
    8. ↵
      1. Bonkhoff H,
      2. Berges R
      . The evolving role of oestrogens and their receptors in the development and progression of prostate cancer. Eur Urol 2009;55:533–42.
      OpenUrlCrossRefPubMed
    9. ↵
      1. Golias Ch,
      2. Iliadis I,
      3. Peschos D,
      4. Charalabopoulos K
      . Amplification and co-regulators of androgen receptor gene in prostate cancer. Exp Oncol 2009;31:3–8.
      OpenUrlPubMed
    10. ↵
      1. Dutt SS,
      2. Gao AC
      . Molecular mechanisms of castration-resistant prostate cancer progression. Future Oncol 2009;5:1403–13.
      OpenUrlCrossRefPubMed
    11. ↵
      1. Freedman ML,
      2. Pearce CL,
      3. Penney KL,
      4. et al
      . Systematic evaluation of genetic variation at the androgen receptor locus and risk of prostate cancer in a multiethnic cohort study. Am J Hum Genet 2005;76:82–90.
      OpenUrlCrossRefPubMed
      1. Thellenberg-Karlsson C,
      2. Lindström S,
      3. Malmer B,
      4. et al
      . Estrogen receptor β polymorphism is associated with prostate cancer risk. Clin Cancer Res 2006;12:1936–41.
      OpenUrlAbstract/FREE Full Text
      1. Nicolaiew N,
      2. Cancel-Tassin G,
      3. Azzouzi AR,
      4. et al
      . Association between estrogen and androgen receptor genes and prostate cancer risk. Eur J Endocrinol 2009;160:101–6.
      OpenUrlAbstract/FREE Full Text
      1. Chae YK,
      2. Huang HY,
      3. Strickland P,
      4. Hoffman SC,
      5. Helzlsouer K
      . Genetic polymorphisms of estrogen receptors α and β and the risk of developing prostate cancer. PLoS One 2009;4:e6523.
      OpenUrlPubMed
      1. Chen YC,
      2. Kraft P,
      3. Bretsky P,
      4. et al
      . Sequence variants of estrogen receptor β and risk of prostate cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium. Cancer Epidemiol Biomarkers Prev 2007;16:1973–81.
      OpenUrlAbstract/FREE Full Text
    12. ↵
      1. McIntyre MH,
      2. Kantoff PW,
      3. Stampfer MJ,
      4. et al
      . Prostate cancer risk and ESR1 TA, ESR2 CA repeat polymorphisms. Cancer Epidemiol Biomarkers Prev 2007;16:2233–6.
      OpenUrlAbstract/FREE Full Text
    13. ↵
      1. Oh WK,
      2. Hayes J,
      3. Evan C,
      4. et al
      . Development of an integrated prostate cancer research information system. Clin Genitourin Cancer 2006;5:61–6.
      OpenUrlPubMed
    14. ↵
      1. Penney KL,
      2. Salinas CA,
      3. Pomerantz M,
      4. et al
      . Evaluation of 8q24 and 17q risk loci and prostate cancer mortality. Clin Cancer Res 2009;15:3223–30.
      OpenUrlAbstract/FREE Full Text
    15. ↵
      1. Patterson N,
      2. Price AL,
      3. Reich D
      . Population structure and eigenanalysis. PLoS Genet 2006;2:e190.
      OpenUrlCrossRefPubMed
    16. ↵
      1. D'Amico AV,
      2. Whittington R,
      3. Malkowicz SB,
      4. et al
      . Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA 1998;280:969–74.
      OpenUrlCrossRefPubMed
    17. ↵
      1. Ross RW,
      2. Oh WK,
      3. Xie W,
      4. et al
      . Inherited variation in the androgen pathway is associated with the efficacy of androgen-deprivation therapy in men with prostate cancer. J Clin Oncol 2008;26:842–7.
      OpenUrlAbstract/FREE Full Text
    18. ↵
      1. Ross RW,
      2. Xie W,
      3. Regan MM,
      4. et al
      . Efficacy of androgen deprivation therapy (ADT) in patients with advanced prostate cancer: association between Gleason score, prostate-specific antigen level, and prior ADT exposure with duration of ADT effect. Cancer 2008;112:1247–53.
      OpenUrlCrossRefPubMed
    19. ↵
      1. de Bakker PI,
      2. Yelensky R,
      3. Pe'er I,
      4. Gabriel SB,
      5. Daly MJ,
      6. Altshuler D
      . Efficiency and power in genetic association studies. Nat Genet 2005;37:1217–23.
      OpenUrlCrossRefPubMed
    20. ↵
      Available from: http://www.broad.mit.edu/mpg/haploview.
    21. ↵
      1. Lindström S,
      2. Adami HO,
      3. Bälter KA,
      4. et al
      . Inherited variation in hormone-regulating genes and prostate cancer survival. Clin Cancer Res 2007;13:5156–61.
      OpenUrlAbstract/FREE Full Text
    View Abstract
    PreviousNext
    Back to top
    Cancer Epidemiology Biomarkers & Prevention: 19 (7)
    July 2010
    Volume 19, Issue 7
    • Table of Contents
    • Table of Contents (PDF)
    • Index by Author

    Sign up for alerts

    View this article with LENS

    Open full page PDF
    Article Alerts
    Sign In to Email Alerts with your Email Address
    Email Article

    Thank you for sharing this Cancer Epidemiology, Biomarkers & Prevention article.

    NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

    Enter multiple addresses on separate lines or separate them with commas.
    Inherited Variations in AR, ESR1, and ESR2 Genes Are Not Associated With Prostate Cancer Aggressiveness or With Efficacy of Androgen Deprivation Therapy
    (Your Name) has forwarded a page to you from Cancer Epidemiology, Biomarkers & Prevention
    (Your Name) thought you would be interested in this article in Cancer Epidemiology, Biomarkers & Prevention.
    Citation Tools
    Inherited Variations in AR, ESR1, and ESR2 Genes Are Not Associated With Prostate Cancer Aggressiveness or With Efficacy of Androgen Deprivation Therapy
    Tong Sun, Gwo-Shu Mary Lee, Lillian Werner, Mark Pomerantz, William K. Oh, Philip W. Kantoff and Matthew L. Freedman
    Cancer Epidemiol Biomarkers Prev July 1 2010 (19) (7) 1871-1878; DOI: 10.1158/1055-9965.EPI-10-0216

    Citation Manager Formats

    • BibTeX
    • Bookends
    • EasyBib
    • EndNote (tagged)
    • EndNote 8 (xml)
    • Medlars
    • Mendeley
    • Papers
    • RefWorks Tagged
    • Ref Manager
    • RIS
    • Zotero
    Share
    Inherited Variations in AR, ESR1, and ESR2 Genes Are Not Associated With Prostate Cancer Aggressiveness or With Efficacy of Androgen Deprivation Therapy
    Tong Sun, Gwo-Shu Mary Lee, Lillian Werner, Mark Pomerantz, William K. Oh, Philip W. Kantoff and Matthew L. Freedman
    Cancer Epidemiol Biomarkers Prev July 1 2010 (19) (7) 1871-1878; DOI: 10.1158/1055-9965.EPI-10-0216
    del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
    • Tweet Widget
    • Facebook Like
    • Google Plus One

    Jump to section

    • Article
      • Abstract
      • Introduction
      • Materials and Methods
      • Results
      • Discussion
      • Disclosure of Potential Conflicts of Interest
      • Acknowledgments
      • Footnotes
      • References
    • Figures & Data
    • Info & Metrics
    • PDF
    Advertisement

    Related Articles

    Cited By...

    More in this TOC Section

    • mtDNA hapogroups and cSCC risk
    • Metformin Not Associated with Risk of Non-Hodgkin Lymphomas
    • Family History of Cancer and Biliary Tract Cancer Risk
    Show more Null Results in Brief
    • Home
    • Alerts
    • Feedback
    Facebook   Twitter   LinkedIn   YouTube   RSS

    Articles

    • Online First
    • Current Issue
    • Past Issues

    Info for

    • Authors
    • Subscribers
    • Advertisers
    • Librarians
    • Reviewers

    About Cancer Epidemiology, Biomarkers & Prevention

    • About the Journal
    • Editorial Board
    • Permissions
    • Submit a Manuscript
    AACR logo

    Copyright © 2018 by the American Association for Cancer Research.

    Cancer Epidemiology, Biomarkers & Prevention
    eISSN: 1538-7755
    ISSN: 1055-9965

    Advertisement