Britton Trabert1, Tim Waterboer2, Annika Idahl3, Nicole Brenner2, Louise A Brinton1, Julia Butt2, Sally B Coburn1, Patricia Hartge1, Katrin Hufnagel2, Federica Inturrisi2, Jolanta Lissowska4, Alexander Mentzer5, Beata Peplonska6, Mark E Sherman7, Gillian S Wills8, Sarah C Woodhall9,10,11, Michael Pawlita12, Nicolas Wentzensen1. 1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD. 2. Infections and Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. 3. Department of Clinical Science, Obstetrics and Gynecology, Umeå University, Umeå, Sweden. 4. Department of Epidemiology and Cancer Prevention, Cancer Center and M. Sklodowska-Curie Institute of Oncology, Warsaw, Poland. 5. Wellcome Centre for Human Genetics, Oxford, UK. 6. Department of Environmental Epidemiology, Nofer Institute of Occupational Medicine, Lodz, Poland. 7. Department of Pulmonary Medicine, Mayo Clinic, Jacksonville, FL. 8. Jefferiss Research Trust Laboratories, Imperial College London, St Mary's Campus, London, UK. 9. National Infection Service, Public Health England, London, UK. 10. Research Department of Infection and Population Health, UCL, London, UK. 11. Gloucestershire Hospitals NHS Foundation Trust, Cheltenham, UK. 12. Molecular Diagnostics of Oncogenic Infections Division, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Abstract
BACKGROUND: Pelvic inflammatory disease (PID) has been associated with ovarian cancer risk. To clarify the role of Chlamydia trachomatis and other infectious agents in the development of ovarian cancer, we evaluated the association of serologic markers with incident ovarian cancer using a staged approach in two independent populations. METHODS: Studies included: 1) a case-control study in Poland (244 ovarian cancers/556 control subjects) and 2) a prospective nested case-control study in the PLCO Cancer Screening Trial (160 ovarian cancers/159 control subjects). Associations of serologic marker levels with ovarian cancer risk at diagnostic as well as higher thresholds, identified in Poland and independently evaluated in PLCO, were estimated using multivariable adjusted logistic regression. RESULTS: In the Polish study, antibodies (based on laboratory cut-point) against the chlamydia plasmid-encoded Pgp3 protein (serological gold standard) were associated with increased ovarian cancer risk (adjusted odds ratio [OR] = 1.63, 95% confidence interval [CI] = 1.20 to 2.22); when a positive result was redefined at higher levels, ovarian cancer risk was increased (cut-point 2: OR = 2.00, 95% CI = 1.38 to 2.89; cut-point 3 [max OR]: OR = 2.19, 95% CI = 1.29 to 3.73). In the prospective PLCO study, Pgp3 antibodies were associated with elevated risk at the laboratory cut-point (OR = 1.43, 95% CI = 0.78 to 2.63) and more stringent cut-points (cut-point 2: OR = 2.25, 95% CI = 1.07 to 4.71); cut-point 3: OR = 2.53, 95% CI = 0.63 to 10.08). In both studies, antibodies against other infectious agents measured were not associated with risk. CONCLUSIONS: In two independent populations, antibodies against prior/current C. trachomatis (Pgp3) were associated with a doubling in ovarian cancer risk, whereas markers of other infectious agents were unrelated. These findings lend support for an association between PID and ovarian cancer. Published by Oxford University Press 2018.
BACKGROUND:Pelvic inflammatory disease (PID) has been associated with ovarian cancer risk. To clarify the role of Chlamydia trachomatis and other infectious agents in the development of ovarian cancer, we evaluated the association of serologic markers with incident ovarian cancer using a staged approach in two independent populations. METHODS: Studies included: 1) a case-control study in Poland (244 ovarian cancers/556 control subjects) and 2) a prospective nested case-control study in the PLCO Cancer Screening Trial (160 ovarian cancers/159 control subjects). Associations of serologic marker levels with ovarian cancer risk at diagnostic as well as higher thresholds, identified in Poland and independently evaluated in PLCO, were estimated using multivariable adjusted logistic regression. RESULTS: In the Polish study, antibodies (based on laboratory cut-point) against the chlamydia plasmid-encoded Pgp3 protein (serological gold standard) were associated with increased ovarian cancer risk (adjusted odds ratio [OR] = 1.63, 95% confidence interval [CI] = 1.20 to 2.22); when a positive result was redefined at higher levels, ovarian cancer risk was increased (cut-point 2: OR = 2.00, 95% CI = 1.38 to 2.89; cut-point 3 [max OR]: OR = 2.19, 95% CI = 1.29 to 3.73). In the prospective PLCO study, Pgp3 antibodies were associated with elevated risk at the laboratory cut-point (OR = 1.43, 95% CI = 0.78 to 2.63) and more stringent cut-points (cut-point 2: OR = 2.25, 95% CI = 1.07 to 4.71); cut-point 3: OR = 2.53, 95% CI = 0.63 to 10.08). In both studies, antibodies against other infectious agents measured were not associated with risk. CONCLUSIONS: In two independent populations, antibodies against prior/current C. trachomatis (Pgp3) were associated with a doubling in ovarian cancer risk, whereas markers of other infectious agents were unrelated. These findings lend support for an association between PID and ovarian cancer. Published by Oxford University Press 2018.
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