TY - JOUR
T1 - Low T-cell subsets prior to development of virus-associated cancer in HIV-seronegative men who have sex with men
AU - Dutta, Anupriya
AU - Uno, Hajime
AU - Lorenz, David R.
AU - Wolinsky, Steven M.
AU - Gabuzda, Dana
N1 - Funding Information:
Acknowledgments Data for this manuscript were obtained by the Multicenter AIDS Cohort Study (MACS) with centers at Baltimore (U01-AI35042): The Johns Hopkins University Bloomberg School of Public Health: Joseph B. Margolick (PI), Jay Bream, Todd Brown, Barbara Crain, Adrian Dobs, Richard Elion, Richard Elion, Michelle Estrella, Lisette Johnson-Hill, Sean Leng, Anne Monroe, Cynthia Munro, Michael W. Plankey, Wendy Post, Ned Sacktor, Jennifer Schrack, Chloe Thio; Chicago (U01-AI35039): Feinberg School of Medicine, Northwestern University, and Cook County Bureau of Health Services: Steven M. Wolinsky (PI), John P. Phair, Sheila Badri, Dana Gabuzda, David Ostrow, Frank J. Palella, Jr., Sudhir Penugonda, Susheel Reddy, Matthew Stephens, Linda Teplin; Los Angeles (U01-AI35040): University of California, UCLA Schools of Public Health and Medicine: Roger Detels (PI), Otoniel Martínez-Maza (Co-PI), Aaron Aronow, Peter Anton, Robert Bolan, Elizabeth Breen, Anthony Butch, Shehnaz Hussain, Beth Jamieson, Eric N. Miller, John Oishi, Harry Vinters, Dorothy Wiley, Mallory Witt, Otto Yang, Stephen Young, Zuo Feng Zhang; Pittsburgh (U01-AI35041): University of Pittsburgh, Graduate School of Public Health: Charles R. Rinaldo (PI), Lawrence A. Kingsley (Co-PI), James T. Becker, Phalguni Gupta, Kenneth Ho, Susan Koletar, Jeremy J. Martinson, John W. Mellors, Anthony J. Silvestre, Ronald D. Stall; Data Coordinating Center (UM1-AI35043): The Johns Hopkins University Bloomberg School of Public Health: Lisa P. Jacobson (PI), Gypsyamber D’Souza (Co-PI), Alison, Abraham, Keri Althoff, Jennifer Deal, Priya Duggal, Sabina Haberlen, Alvaro Muoz, Derek Ng, Janet Schollenberger, Eric C. Seaberg, Sol Su, Pamela Surkan. Website located at http://www.statepi.jhsph.edu/macs/ macs.html. Cancer incidence data were provided by the following state agencies: (1) Maryland Cancer Registry, Center for Cancer Prevention and Control, Department of Health and Mental Hygiene, Baltimore, MD 21201; (2) Illinois Department of Public Health, Illinois State Cancer Registry; (3) Bureau of Health Statistics & Research, Pennsylvania Department of Health, Harrisburg, Pennsylvania; (4) Ohio Cancer Incidence Surveillance System (OCISS), Ohio Department of Health (ODH), a cancer registry partially supported in the National Program of Cancer Registries at the Centers for Disease Control and Prevention (CDC) through Cooperative Agreement # 5U58DP000795-05; and (5) California Department of Public Health pursuant to California Health and Safety Code Section 103885; CDC’s National Program of Cancer Registries, under cooperative agreement 5NU58DP003862-04/ DP003862; the National Cancer Institute’s Surveillance, Epidemiology and End Results Program under contract HHSN261201000140C awarded to the Cancer Prevention Institute of California, contract HHSN261201000035C awarded to the University of Southern California, and contract HHSN261201000034C awarded to the Public Health Institute. We acknowledge the State of Maryland, the Maryland Cigarette Restitution Fund, and the National Program of Cancer Registries of the CDC for the funds that support the collection and availability of the cancer registry data. The analyses, findings, interpretations, and conclusions of this report are those of the authors. No endorsement by any of the states providing data, the National Cancer Institute, the CDC, or their Contractors and Subcontractors is intended nor should be inferred. The authors also acknowledge Dr. Isaac Solomon for helpful discussions of primary data and Elizabeth Carpelan for assistance with manuscript preparation.
Funding Information:
Funding This work was supported by NIH Grants to D.G. (DP1 DA028994, R01 DA30985, and R01 DA40391). The work was also supported in part by NIH funding to the Northwestern University Clinical Research Unit of the MACS (U01-AI35039), with additional co-funding from the National Cancer Institute (NCI), National Institute on Drug Abuse (NIDA), and National Institute of Mental Health (NIMH). A.D. was supported in part by NIH T32-AG000222 and T32-AI007386. Biostatistical consultation was provided by the NIH-funded Harvard Catalyst (UL1 TR001102). The MACS is funded by the National Institute of Allergy and Infectious Diseases (NIAID) [U01-AI35039, U01-AI35040; U01-AI35041; U01-AI35042; and UM1-AI35043], with additional co-funding from the National Cancer Institute (NCI), National Institute on Drug Abuse (NIDA), and National Institute of Mental Health (NIMH) at the National Institutes of Health (NIH). MACS data collection is also supported by UL1-TR000424 (JHU CTSA).
Publisher Copyright:
© 2018, The Author(s).
PY - 2018/11/1
Y1 - 2018/11/1
N2 - Immunological parameters that influence susceptibility to virus-associated cancers in HIV-seronegative individuals are unclear. We conducted a case–control cohort study of immunological parameters associated with development of incident virus-associated cancers among 532 HIV-seronegative men who have sex with men (MSM) enrolled in the Multicenter AIDS Cohort Study (MACS) with median (IQR) 21 (8–26) years of follow-up. Thirty-two incident virus-associated cancers (anal cancer, non-Hodgkin lymphoma, liver cancer, other cancers with etiologies linked to human papillomavirus, Epstein–Barr virus, hepatitis B virus, or human herpesvirus-8) were identified among 3,408 HIV-seronegative men in the MACS during 1984–2010. Cases were matched for demographics, smoking, and follow-up to 500 controls without cancer. Mixed-effects and Cox regression models were used to examine associations between nadir or recent CD4, CD8, and white blood cell (WBC) counts or CD4:CD8 ratios and subsequent diagnosis of virus-associated cancers. Men with incident virus-associated cancers had lower CD4 and WBC counts over a 6-year window prior to diagnosis compared to men without cancer (p = 0.001 and 0.03, respectively). Low CD4 cell count and nadir, CD4 count-nadir differential, and CD4:CD8 ratio nadir were associated with increased 2-year risk of incident virus-associated cancers in models adjusted for demographics and smoking (hazard ratios 1.2–1.3 per 100 or 0.1 unit decrease, respectively; p < 0.01). Other associated factors included heavy smoking and past or current hepatitis B virus infection. These findings show that low CD4 cell counts, CD4 nadir, and CD4:CD8 cell ratios are independent predictors for subsequent risk of virus-associated cancers in HIV-seronegative MSM.
AB - Immunological parameters that influence susceptibility to virus-associated cancers in HIV-seronegative individuals are unclear. We conducted a case–control cohort study of immunological parameters associated with development of incident virus-associated cancers among 532 HIV-seronegative men who have sex with men (MSM) enrolled in the Multicenter AIDS Cohort Study (MACS) with median (IQR) 21 (8–26) years of follow-up. Thirty-two incident virus-associated cancers (anal cancer, non-Hodgkin lymphoma, liver cancer, other cancers with etiologies linked to human papillomavirus, Epstein–Barr virus, hepatitis B virus, or human herpesvirus-8) were identified among 3,408 HIV-seronegative men in the MACS during 1984–2010. Cases were matched for demographics, smoking, and follow-up to 500 controls without cancer. Mixed-effects and Cox regression models were used to examine associations between nadir or recent CD4, CD8, and white blood cell (WBC) counts or CD4:CD8 ratios and subsequent diagnosis of virus-associated cancers. Men with incident virus-associated cancers had lower CD4 and WBC counts over a 6-year window prior to diagnosis compared to men without cancer (p = 0.001 and 0.03, respectively). Low CD4 cell count and nadir, CD4 count-nadir differential, and CD4:CD8 ratio nadir were associated with increased 2-year risk of incident virus-associated cancers in models adjusted for demographics and smoking (hazard ratios 1.2–1.3 per 100 or 0.1 unit decrease, respectively; p < 0.01). Other associated factors included heavy smoking and past or current hepatitis B virus infection. These findings show that low CD4 cell counts, CD4 nadir, and CD4:CD8 cell ratios are independent predictors for subsequent risk of virus-associated cancers in HIV-seronegative MSM.
KW - CD4 T cells
KW - CD8 T cells
KW - Cancer risk
KW - HBV
KW - Lymphopenia
KW - Oncogenic viruses
UR - http://www.scopus.com/inward/record.url?scp=85055290758&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85055290758&partnerID=8YFLogxK
U2 - 10.1007/s10552-018-1090-4
DO - 10.1007/s10552-018-1090-4
M3 - Article
C2 - 30315476
AN - SCOPUS:85055290758
VL - 29
SP - 1131
EP - 1142
JO - Cancer Causes and Control
JF - Cancer Causes and Control
SN - 0957-5243
IS - 11
ER -