UCSF, VA investigations find “clear evidence” of misconduct in cancer papers

Earlier this year, the University of California, San Francisco and the San Francisco Veterans Administration Medical Center teamed up to write a letter.

Addressed to the editorial office at the American Association of Cancer Research (AACR), the letter, parts of which have been published in a retraction notice, contained information concerning two papers on genetic risk factors for a type of kidney cancer and a type of uterine cancer, respectively, published in different AACR journals over a decade ago by researchers affiliated with the institutions.

The papers had been at the center of research misconduct investigations at both UCSF and the VA and the investigations came to the conclusion that both papers contained:

fabrication or falsification of data that constitutes Research Misconduct.

Though one of the papers has been retracted, it’s unclear what will happen to the other. [Note: See update at the bottom of the post.]Polymorphisms of the CYP1B1 Gene as Risk Factors for Human Renal Cell Cancer,” published in 2004 in Clinical Cancer Research, was retracted on Sept. 1. It has been cited 31 times, according to Clarivate Analytics’ Web of Science. There’s a conference abstract with the same title indexed in PubMed, but it has not been cited.

The other paper in question is “CYP1B1 Gene Polymorphisms Have Higher risk for Endometrial Cancer, and Positive Correlations with Estrogen Receptor α and Estrogen Receptor β Expressions,” originally published in 2003 in Cancer Research, which has been cited 62 times.

The retraction notice — a more thorough one than we usually see — often quotes the joint letter verbatim, adding that:

The two articles had some figures with the same panels used for both papers despite being experiments from two different cancers. The figures also have some panels repeated from and identical to an earlier paper studying a third type of cancer.

We haven’t been able to determine exactly when the UCSF and VA investigations started. We requested a copy of the letter sent to AACR, but Terri O’Lonergan, UCSF assistant vice chancellor and chief ethics and compliance officer, told us she would first have to determine whether it was a public document and, even if it were, that she would only release it with the agreement of the VA.

There is, however, a four-year-old thread on PubPeer, suggesting that multiple figures in each of the two papers contain suspiciously similar gel bands. Primarily, the initial PubPeer commenter noted that bands from figure 1B in each paper appeared to be the same.

The UCSF and VA investigations confirmed that those figures 1B were similar and that they indicated research misconduct. The letter, as quoted in the retraction notice, said:

The Investigation Committee reviewed in detail the analytic methods and findings of the Inquiry Committee. It unanimously agreed that there were numerous similarities between the figures in question, including the location and shape of streak and spot artifacts, as well as band morphologies were noted. This was concluded by the Committee to support the allegation of data falsification or fabrication and research misconduct.

The letter represents just one way that universities and local VA medical centers can team up on research misconduct investigations. Readers may recall the story of Azza El-Remessy, a former eye researcher in Georgia who was investigated jointly by two universities and the Charlie Norwood Veterans Affairs Medical Center, in Augusta, Georgia.

But even a joint investigation can lead to contradictory outcomes. In El-Remessy’s case, the VA eventually disagreed with the University of Georgia, and reopened its investigation. Readers may also recall the saga of Christian Kreipke, a former Wayne State University professor and John D. Dingell VA Medical Center researcher, who was the subject of misconduct probes at each institution (Kreipke has disputed the notion that they are separate probes). In Kreipke’s case, both Wayne State and the VA found misconduct and terminated him; however, a federal judge overturned the VA’s decision to fire him for misconduct, saying it had motive to retaliate against him for whistleblowing. Meanwhile, the Wayne State investigation has become the basis for a federal funding ban sought by the Office of Research Integrity in the Department of Health and Human Services.

The UCSF/VA letter also said that several images appeared to originate in third paper, “Polymorphisms of the CYP1B1 gene have higher risk for prostate cancer,” published in August 2002 in Biochemical and Biophysical Research Communications. That paper has been cited 56 times.

The retraction for the Clinical Cancer Research paper is the second for last author Rajvir Dahiya, director of the Urology Research Center at UCSF with a joint appointment at the VA, and co-author Yuichiro Tanaka, also a professor at UCSF. Their first, “Genistein mediated histone acetylation and demethylation activates tumor suppressor genes in prostate cancer cells,” was retracted from the International Journal of Cancer in June and has been cited 139 times.

While the UCSF/VA letter unequivocally said that research misconduct had taken place, it did not specifically ask for the two papers to be retracted. Instead, UCSF and the VA left the final decision up to ACCR, saying that they:

recommend that both Clinical Cancer Research and Cancer Research assess these articles for correction or retraction.

As far as we can tell, Cancer Research has not made any moves to correct or retract the 2003 paper. The journal hasn’t yet responded to our request for comment on the future of that paper.

Update, 18:41 UTC time, September 15, 2017: The other paper has been retracted. You can read the notice here.

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18 thoughts on “UCSF, VA investigations find “clear evidence” of misconduct in cancer papers”

  1. How can they “recommend” the “correction or retraction”?!
    This is in other words saying that they do accept data manipulation and
    do not care about the scientific record.
    They should be clear and DEMAND RETRACTION ASAP.

    1. The University can demand what it wants, it’s just not their decision to make, but that of the journal. Therefore the gentler language is appropriate.

  2. Have any of the investigators looked into whether the papers now known to contain fabrication or falsification were used to obtain grants? If so, how much and from whom?

  3. Oncogene. 2007 Dec 6;26(55):7647-55. Epub 2007 Jun 11.
    Knockdown of astrocyte-elevated gene-1 inhibits prostate cancer progression through upregulation of FOXO3a activity.

    Kikuno N1, Shiina H, Urakami S, Kawamoto K, Hirata H, Tanaka Y, Place RF, Pookot D, Majid S, Igawa M, Dahiya R.
    Author information
    1
    Department of Urology, Veterans Affairs Medical Center and University of California, San Francisco, CA 94121, USA.

    See images here: https://pubpeer.com/publications/B690D4F3DBFD14CC77EEB2BADEB615

  4. Cancer Res. 2003 Jul 15;63(14):3913-8.
    CYP1B1 gene polymorphisms have higher risk for endometrial cancer, and positive correlations with estrogen receptor alpha and estrogen receptor beta expressions.

    Sasaki M1, Tanaka Y, Kaneuchi M, Sakuragi N, Dahiya R.
    Author information
    1
    Department of Urology, University of California San Francisco and Veterans Affairs Medical Center, San Francisco, California 94121, USA.

    https://imgur.com/XjaIJDx

    For reference.
    Biochem Biophys Res Commun. 2002 Aug 30;296(4):820-6.
    Polymorphisms of the CYP1B1 gene have higher risk for prostate cancer.

    Tanaka Y1, Sasaki M, Kaneuchi M, Shiina H, Igawa M, Dahiya R.
    Author information
    1
    Department of Urology, University of California at San Francisco, 4150 Clement Street, San Francisco, CA 94121, USA.

  5. Mol Carcinog. 2001 Sep;32(1):19-27.
    CpG methylation of promoter region inactivates E-cadherin gene in renal cell carcinoma.

    Nojima D1, Nakajima K, Li LC, Franks J, Ribeiro-Filho L, Ishii N, Dahiya R.
    Author information
    1
    Department of Urology, Veterans Affairs Medical Center and University of California San Francisco, 94121, USA.

    Figure 6. https://imgur.com/VPMNXxl

    1. You do so much hard work to find out all the misconduct and scientific corruption but I doubt that it makes much dent into the careers of the so called scientists who are responsible for such acts. They will still publish more papers, retain their positions as Professors, Directors and get more money from the NIH

      1. “I doubt that it makes much dent into the careers of the so called scientists who are responsible for such acts. They will still publish more papers, retain their positions as Professors, Directors and get more money from the NIH”

        My bet is that your prediction will not be true in this case.

  6. J Urol. 2000 Apr;163(4):1339-42.
    Deletion of Y-chromosome specific genes in human prostate cancer.

    Perinchery G1, Sasaki M, Angan A, Kumar V, Carroll P, Dahiya R.
    Author information
    1
    Department of Urology, Veterans Affairs Medical Center, and University of California San Francisco, 94121, USA.

    Figure 1. https://imgur.com/tvoxowD

  7. 2017 retraction.

    Cancer Res. 2003 Jul 15;63(14):3913-8.
    CYP1B1 gene polymorphisms have higher risk for endometrial cancer, and positive correlations with estrogen receptor alpha and estrogen receptor beta expressions.

    Sasaki M1, Tanaka Y, Kaneuchi M, Sakuragi N, Dahiya R.
    Author information
    1
    Department of Urology, University of California San Francisco and Veterans Affairs Medical Center, San Francisco, California 94121, USA.

    2017 retraction notice.
    http://cancerres.aacrjournals.org/content/77/18/5211

  8. 2018 correction for:
    Br J Cancer. 2014 Mar 18;110(6):1645-54. doi: 10.1038/bjc.2014.48. Epub 2014 Feb 6.
    Genistein downregulates onco-miR-1260b and upregulates sFRP1 and Smad4 via demethylation and histone modification in prostate cancer cells.
    Hirata H1, Hinoda Y2, Shahryari V1, Deng G1, Tanaka Y1, Tabatabai ZL3, Dahiya R1.
    Author information
    1 Department of Urology, San Francisco Veterans Affairs Medical Center and University of California at San Francisco, San Francisco, California, USA.
    2 Department of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan.
    3 Department of Pathology, San Francisco Veterans Affairs Medical Center and University of California at San Francisco, San Francisco, California, USA.

    https://pubpeer.com/publications/59C1441BC2B628488D97A67FC456C7

    2018 correction.
    https://www.nature.com/articles/s41416-018-0146-2
    Correction to: British Journal of Cancer 110, 1645–1654 (2014); https://doi.org/10.1038/bjc.2014.48; published online 6 February 2014

    “The authors report that there is a mistake in the representative picture of Fig. 4D (top row: PC3-miR1260b inh-0h) in the original version. The correct version of Fig. 4 with the original pictures for both PC3 miR-NC inh-0h and PC3-miR1260b inh-0h are provided below.”

  9. Data in Int J Cancer. 2011 Feb 1;128(3):541-50. doi: 10.1002/ijc.2535 much more similar to data in Cancer Res. 2009 Nov 15;69(22):8603-10. doi: 10.1158/0008-5472.CAN-09-2534
    than expected.

    Figure 1a Int J Cancer. 2011 Feb 1;128(3):541-50

    See: https://imgur.com/X2emwHQ

    Int J Cancer. 2011 Feb 1;128(3):541-50. doi: 10.1002/ijc.25357.
    Secreted frizzled-related protein-5 is epigenetically downregulated and functions as a tumor suppressor in kidney cancer
    Kazumori Kawakami 1, Soichiro Yamamura, Hiroshi Hirata, Koji Ueno, Sharanjot Saini, Shahana Majid, Yuichiro Tanaka, Ken Kawamoto, Hideki Enokida, Masayuki Nakagawa, Rajvir Dahiya

    Affiliation
    1Department of Urology, Veterans Affairs Medical Center and University of California, San Francisco, CA 94121, USA.

    Cancer Res
    . 2009 Nov 15;69(22):8603-10. doi: 10.1158/0008-5472.CAN-09-2534. Epub 2009 Nov 3.
    Functional significance of Wnt inhibitory factor-1 gene in kidney cancer
    Kazumori Kawakami 1, Hiroshi Hirata, Soichiro Yamamura, Nobuyuki Kikuno, Sharanjot Saini, Shahana Majid, Yuichiro Tanaka, Ken Kawamoto, Hideki Enokida, Masayuki Nakagawa, Rajvir Dahiya

    Affiliation
    1Department of Urology, Veterans Affairs Medical Center and University of California at San Francisco, San Francisco, California 94121, USA.

  10. Cell Physiol Biochem. 2020 Jan 22;54(1):53-70. doi: 10.33594/000000205.
    Genistein Represses HOTAIR/Chromatin Remodeling Pathways to Suppress Kidney Cancer
    Mitsuho Imai-Sumida 1, Pritha Dasgupta 1, Priyanka Kulkarni 1, Marisa Shiina 1, Yutaka Hashimoto 1, Varahram Shahryari 1, Shahana Majid 1, Yuichiro Tanaka 1, Rajvir Dahiya 1, Soichiro Yamamura 2

    Affiliations
    1Department of Urology, San Francisco Veterans Affairs Medical Center and University of California San Francisco, San Francisco, USA.
    2Department of Urology, San Francisco Veterans Affairs Medical Center and University of California San Francisco, San Francisco, USA, [email protected]

    Figure 1. Much more similar than expected.

    https://pubpeer.com/publications/D9AE023FA3F6C283565B2E06763A8D#1

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