BACKGROUND: Laboratory-based, mechanistic, and prognosis studies suggest that a shift from antitumor immunity towards tumor-immune tolerance plays a major role in carcinogenesis. However, prospective epidemiological studies on the consequences of differing immune tolerance levels prior to clinical manifestation are missing. METHODS: A case-cohort study embedded in EPIC-Heidelberg was conducted comprising incident cases of breast (n = 399), colorectal (n = 185), lung (n = 149), and prostate (n = 378) cancer, which occurred during 6.6 years of follow-up, and a subcohort (n = 807). Foxp3+ regulatory T-lymphocytes and CD3+ T-lymphocytes were measured by quantitative polymerase chain reaction-based DNA methylation analysis in prediagnostic leukocyte samples. Hazard ratios (HRs) for associations of cancer risk with the ratio of both parameters, the "cellular ratio of immune tolerance" (ImmunoCRIT), were estimated using Cox regression models. All statistical tests were two-sided. RESULTS: ImmunoCRIT values were positively associated with the risk of lung (highest vs lowest tertile, HR = 1.98, 95% confidence interval = 1.06 to 3.69, P trend = .0263) and colorectal cancer (HR = 1.59, 95% CI = 0.99 to 2.54, P trend = .0069) after multivariable adjustment, but not with prostate cancer risk. Regarding breast cancer significant heterogeneity by estrogen receptor (ER) status was observed (P heterogeneity = .02), and the ImmunoCRIT was associated with the risk of ER-negative breast cancer (HR = 3.34, 95% CI = 1.52 to 7.35, P trend ≤ .001), but not ER-positive breast cancer. CONCLUSION: The present study indicates that increased peripheral immune tolerance may be an independent risk factor for lung, colorectal, and ER-negative breast cancer, whereas its role on the development of prostate and ER-positive breast tumors remains uncertain.
BACKGROUND: Laboratory-based, mechanistic, and prognosis studies suggest that a shift from antitumor immunity towards tumor-immune tolerance plays a major role in carcinogenesis. However, prospective epidemiological studies on the consequences of differing immune tolerance levels prior to clinical manifestation are missing. METHODS: A case-cohort study embedded in EPIC-Heidelberg was conducted comprising incident cases of breast (n = 399), colorectal (n = 185), lung (n = 149), and prostate (n = 378) cancer, which occurred during 6.6 years of follow-up, and a subcohort (n = 807). Foxp3+ regulatory T-lymphocytes and CD3+ T-lymphocytes were measured by quantitative polymerase chain reaction-based DNA methylation analysis in prediagnostic leukocyte samples. Hazard ratios (HRs) for associations of cancer risk with the ratio of both parameters, the "cellular ratio of immune tolerance" (ImmunoCRIT), were estimated using Cox regression models. All statistical tests were two-sided. RESULTS: ImmunoCRIT values were positively associated with the risk of lung (highest vs lowest tertile, HR = 1.98, 95% confidence interval = 1.06 to 3.69, P trend = .0263) and colorectal cancer (HR = 1.59, 95% CI = 0.99 to 2.54, P trend = .0069) after multivariable adjustment, but not with prostate cancer risk. Regarding breast cancer significant heterogeneity by estrogen receptor (ER) status was observed (P heterogeneity = .02), and the ImmunoCRIT was associated with the risk of ER-negative breast cancer (HR = 3.34, 95% CI = 1.52 to 7.35, P trend ≤ .001), but not ER-positive breast cancer. CONCLUSION: The present study indicates that increased peripheral immune tolerance may be an independent risk factor for lung, colorectal, and ER-negative breast cancer, whereas its role on the development of prostate and ER-positive breast tumors remains uncertain.
Authors: Danja Sarink; Helena Schock; Theron Johnson; Kim Overvad; Marianne Holm; Anne Tjønneland; Marie-Christine Boutron-Ruault; Mathilde His; Marina Kvaskoff; Heiner Boeing; Pagona Lagiou; Eleni-Maria Papatesta; Antonia Trichopoulou; Domenico Palli; Valeria Pala; Amalia Mattiello; Rosario Tumino; Carlotta Sacerdote; H B As Bueno-de-Mesquita; Carla H van Gils; Petra H Peeters; Elisabete Weiderpass; Antonio Agudo; Maria-José Sánchez; Maria-Dolores Chirlaque; Eva Ardanaz; Pilar Amiano; Kay Tee Khaw; Ruth Travis; Laure Dossus; Mark Gunter; Sabina Rinaldi; Melissa Merritt; Elio Riboli; Rudolf Kaaks; Renée T Fortner Journal: Cancer Prev Res (Phila) Date: 2017-07-12
Authors: Mingyang Song; Reiko Nishihara; Yin Cao; Eunyoung Chun; Zhi Rong Qian; Kosuke Mima; Kentaro Inamura; Yohei Masugi; Jonathan A Nowak; Katsuhiko Nosho; Kana Wu; Molin Wang; Edward Giovannucci; Wendy S Garrett; Charles S Fuchs; Shuji Ogino; Andrew T Chan Journal: JAMA Oncol Date: 2016-09-01 Impact factor: 31.777
Authors: Chi-Chen Hong; Lara E Sucheston-Campbell; Song Liu; Qiang Hu; Song Yao; Kathryn L Lunetta; Stephen A Haddad; Edward A Ruiz-Narváez; Jeannette T Bensen; Ting-Yuan David Cheng; Elisa V Bandera; Lynn A Rosenberg; Christopher A Haiman; Kelvin Lee; Sharon S Evans; Scott I Abrams; Elizabeth A Repasky; Andrew F Olshan; Julie R Palmer; Christine B Ambrosone Journal: Cancer Epidemiol Biomarkers Prev Date: 2018-01-16 Impact factor: 4.254
Authors: Jianda Yuan; Priti S Hegde; Raphael Clynes; Periklis G Foukas; Alexandre Harari; Thomas O Kleen; Pia Kvistborg; Cristina Maccalli; Holden T Maecker; David B Page; Harlan Robins; Wenru Song; Edward C Stack; Ena Wang; Theresa L Whiteside; Yingdong Zhao; Heinz Zwierzina; Lisa H Butterfield; Bernard A Fox Journal: J Immunother Cancer Date: 2016-01-19 Impact factor: 13.751
Authors: David Capper; Andreas von Deimling; Alba A Brandes; Antoine F Carpentier; Santosh Kesari; Juan M Sepulveda-Sanchez; Helen R Wheeler; Olivier Chinot; Lawrence Cher; Joachim P Steinbach; Pol Specenier; Jordi Rodon; Ann Cleverly; Claire Smith; Ivelina Gueorguieva; Colin Miles; Susan C Guba; Durisala Desaiah; Shawn T Estrem; Michael M Lahn; Wolfgang Wick Journal: Int J Mol Sci Date: 2017-05-06 Impact factor: 5.923