Calcium intake and risk of colorectal cancer according to tumor-infiltrating T cells

Wanshui Yang, Li Liu, Na Na Keum, Zhi Rong Qian, Jonathan A. Nowak, Tsuyoshi Hamada, Mingyang Song, Yin Cao, Katsuhiko Nosho, Stephanie A. Smith-Warner, Sui Zhang, Yohei Masugi, Kimmie Ng, Keisuke Kosumi, Yanan Ma, Wendy S. Garrett, Molin Wang, Hongmei Nan, Marios Giannakis, Jeffrey A. MeyerhardtAndrew T. Chan, Charles S. Fuchs, Reiko Nishihara, Kana Wu, Edward L. Giovannucci, Shuji Ogino, Xuehong Zhang

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3 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)283-293
Number of pages11
JournalCancer Prevention Research
Volume12
Issue number5
DOIs
StatePublished - May 2019

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Yang, W., Liu, L., Keum, N. N., Qian, Z. R., Nowak, J. A., Hamada, T., Song, M., Cao, Y., Nosho, K., Smith-Warner, S. A., Zhang, S., Masugi, Y., Ng, K., Kosumi, K., Ma, Y., Garrett, W. S., Wang, M., Nan, H., Giannakis, M., ... Zhang, X. (2019). Calcium intake and risk of colorectal cancer according to tumor-infiltrating T cells. Cancer Prevention Research, 12(5), 283-293. https://doi.org/10.1158/1940-6207.CAPR-18-0279