TY - JOUR
T1 - Calcium intake and risk of colorectal cancer according to tumor-infiltrating T cells
AU - Yang, Wanshui
AU - Liu, Li
AU - Keum, Na Na
AU - Qian, Zhi Rong
AU - Nowak, Jonathan A.
AU - Hamada, Tsuyoshi
AU - Song, Mingyang
AU - Cao, Yin
AU - Nosho, Katsuhiko
AU - Smith-Warner, Stephanie A.
AU - Zhang, Sui
AU - Masugi, Yohei
AU - Ng, Kimmie
AU - Kosumi, Keisuke
AU - Ma, Yanan
AU - Garrett, Wendy S.
AU - Wang, Molin
AU - Nan, Hongmei
AU - Giannakis, Marios
AU - Meyerhardt, Jeffrey A.
AU - Chan, Andrew T.
AU - Fuchs, Charles S.
AU - Nishihara, Reiko
AU - Wu, Kana
AU - Giovannucci, Edward L.
AU - Ogino, Shuji
AU - Zhang, Xuehong
N1 - Funding Information:
K. Ng reports receiving commercial research grant from Pharmavite, Genentech, Tarrex Biopharma, and Gilead and is a consultant/advisory board member for Bayer, Seattle Genetics, and Tarrex. W.S. Garrett reports receiving speakers bureau honoraria from Merck, Janssen, and Pfizer and is a consultant/advisory board member for BiomX, Kintai Therapeutics, and Evelo Biosciences. M. Giannakis is a consultant/advisory board member for AstraZeneca. C.S. Fuchs is a consultant/advisory board member for Merck, Entrinsic Health, CytomX, Taiho Pharmaceutical, Sanofi, Eli Lilly, and Unum Therapeutics. No potential conflicts of interest were disclosed by the other authors.
Funding Information:
We would like to thank the participants and staff of the Nurses' Health Study and Health Professionals Follow-up Study for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. This work was supported by the NIH (P01 CA87969 and UM1 CA186107, to M.J. Stampfer; P01 CA55075 and UM1 CA167552 to W.C. Willett; U01 CA167552 to W.C. Willett and L.A. Mucci; P50 CA127003, R01 CA118553, R01 CA169141, R01 CA137178, and K24 DK098311 to A.T. Chan; R01 CA205406 to K. Ng.; R01 CA151993 and R35 CA197735 to S. Ogino; K07 CA190673 to R. Nishihara; and R03 CA176717 and K07 CA188126 to X. Zhang); Nodal Award (to S. Ogino) from the Dana-Farber Harvard Cancer Center; Research supported by a Stand Up To Cancer Colorectal Cancer Dream Team Translational Research Grant (grant no.: SU2C-AACR-DT22-17) to C.S. Fuchs Stand Up To Cancer is a division of the Entertainment Industry Foundation. Research grants are administered by the American Association for Cancer Research, the Scientific Partner of SU2C; and by grants from The Project P Fund for Colorectal Cancer Research, The Friends of the Dana-Farber Cancer Institute, Bennett Family Fund, and the Entertainment Industry Foundation through National Colorectal Cancer Research Alliance. W. Yang and L. Liu were supported by scholarship grants from Chinese Scholarship Council. L. Liu was also supported by a fellowship grant from Huazhong University of Science and Technology. K. Kosumi was supported by the JSPS Overseas Research Fellowships grant from the Japan Society for the Promotion of Science (JP2017-775).
Publisher Copyright:
© 2019 American Association for Cancer Research.
PY - 2019/5
Y1 - 2019/5
N2 - Calcium intake has been associated with a lower risk 0.36–0.84; Ptrend ¼ 0.002) for CD8þ T-cell–low but not of colorectal cancer. Calcium signaling may enhance for CD8þ T-cell–high tumors (HR ¼ 1.02; 95% CI, T-cell proliferation and differentiation, and contribute 0.67–1.55; Ptrend ¼ 0.47). Similarly, the corresponding to T-cell–mediated antitumor immunity. In this pro-HRs (95% CIs) for calcium for low versus high T-cell–spective cohort study, we investigated the association infiltrated tumors were 0.63 (0.42–0.94; Ptrend ¼ 0.01) between calcium intake and colorectal cancer risk and 0.89 (0.58–1.35; Ptrend ¼ 0.20) for CD3þ; according to tumor immunity status to provide addi-0.58 (0.39–0.87; Ptrend ¼ 0.006) and 1.04 (0.69–tional insights into the role of calcium in colorectal 1.58; Ptrend ¼ 0.54) for CD45ROþ; and 0.56 (0.36–carcinogenesis. The densities of tumor-infiltrating 0.85; Ptrend ¼ 0.006) and 1.10 (0.72–1.67; Ptrend ¼ T-cell subsets [CD3þ, CD8þ, CD45RO (PTPRC)þ, or 0.47) for FOXP3þ, although the differences by sub-FOXP3þ cell] were assessed using IHC and computer-types defined by T-cell density were not statistically assisted image analysis in 736 cancer cases that devel-significant. These potential differential associations oped among 136,249 individuals in two cohorts. HRs generally appeared consistent regardless of sex, source and 95% confidence intervals (CI) were calculated of calcium intake, tumor location, and tumor micro-using Cox proportional hazards regression. Total cal-satellite instability status. Our findings suggest a pos-cium intake was associated with a multivariable HR of sible role of calcium in cancer immunoprevention via 0.55 (comparing 1,200 vs. <600 mg/day; 95% CI, modulation of T-cell function.
AB - Calcium intake has been associated with a lower risk 0.36–0.84; Ptrend ¼ 0.002) for CD8þ T-cell–low but not of colorectal cancer. Calcium signaling may enhance for CD8þ T-cell–high tumors (HR ¼ 1.02; 95% CI, T-cell proliferation and differentiation, and contribute 0.67–1.55; Ptrend ¼ 0.47). Similarly, the corresponding to T-cell–mediated antitumor immunity. In this pro-HRs (95% CIs) for calcium for low versus high T-cell–spective cohort study, we investigated the association infiltrated tumors were 0.63 (0.42–0.94; Ptrend ¼ 0.01) between calcium intake and colorectal cancer risk and 0.89 (0.58–1.35; Ptrend ¼ 0.20) for CD3þ; according to tumor immunity status to provide addi-0.58 (0.39–0.87; Ptrend ¼ 0.006) and 1.04 (0.69–tional insights into the role of calcium in colorectal 1.58; Ptrend ¼ 0.54) for CD45ROþ; and 0.56 (0.36–carcinogenesis. The densities of tumor-infiltrating 0.85; Ptrend ¼ 0.006) and 1.10 (0.72–1.67; Ptrend ¼ T-cell subsets [CD3þ, CD8þ, CD45RO (PTPRC)þ, or 0.47) for FOXP3þ, although the differences by sub-FOXP3þ cell] were assessed using IHC and computer-types defined by T-cell density were not statistically assisted image analysis in 736 cancer cases that devel-significant. These potential differential associations oped among 136,249 individuals in two cohorts. HRs generally appeared consistent regardless of sex, source and 95% confidence intervals (CI) were calculated of calcium intake, tumor location, and tumor micro-using Cox proportional hazards regression. Total cal-satellite instability status. Our findings suggest a pos-cium intake was associated with a multivariable HR of sible role of calcium in cancer immunoprevention via 0.55 (comparing 1,200 vs. <600 mg/day; 95% CI, modulation of T-cell function.
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U2 - 10.1158/1940-6207.CAPR-18-0279
DO - 10.1158/1940-6207.CAPR-18-0279
M3 - Article
C2 - 30760501
AN - SCOPUS:85065511115
VL - 12
SP - 283
EP - 293
JO - Cancer Prevention Research
JF - Cancer Prevention Research
SN - 1940-6207
IS - 5
ER -