Tumor expression of calcium sensing receptor and colorectal cancer survival: Results from the nurses’ health study and health professionals follow-up study

Fatemeh Momen-Heravi, Yohei Masugi, Zhi Rong Qian, Reiko Nishihara, Li Liu, Stephanie A. Smith-Warner, Na Na Keum, Lanjing Zhang, Nairi Tchrakian, Jonathan A. Nowak, Wanshui Yang, Yanan Ma, Michaela Bowden, Annacarolina da Silva, Molin Wang, Charles S. Fuchs, Jeffrey A. Meyerhardt, Kimmie Ng, Kana Wu, Edward GiovannucciShuji Ogino, Xuehong Zhang

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Although experimental evidence suggests calcium-sensing receptor (CASR) as a tumor-suppressor, the prognostic role of tumor CASR expression in colorectal carcinoma remains unclear. We hypothesized that higher tumor CASR expression might be associated with improved survival among colorectal cancer patients. We evaluated tumor expression levels of CASR by immunohistochemistry in 809 incident colorectal cancer patients within the Nurses' Health Study and the Health Professionals Follow-up Study. We used Cox proportional hazards regression models to estimate multivariable hazard ratio (HR) for the association of tumor CASR expression with colorectal cancer-specific and all-cause mortality. We adjusted for potential confounders including tumor biomarkers such as microsatellite instability, CpG island methylator phenotype, LINE-1 methylation level, expressions of PTGS2, VDR and CTNNB1 and mutations of KRAS, BRAF and PIK3CA. There were 240 colorectal cancer-specific deaths and 427 all-cause deaths. The median follow-up of censored patients was 10.8 years (interquartile range: 7.2, 15.1). Compared with patients with no or weak expression of CASR, the multivariable HRs for colorectal cancer-specific mortality were 0.80 [95% confidence interval (CI): 0.55–1.16] in patients with moderate CASR expression and 0.50 (95% CI: 0.32–0.79) in patients with intense CASR expression (p-trend = 0.003). The corresponding HRs for overall mortality were 0.85 (0.64–1.13) and 0.81 (0.58–1.12), respectively. Higher tumor CASR expression was associated with a lower risk of colorectal cancer-specific mortality. This finding needs further confirmation and if confirmed, may lead to better understanding of the role of CASR in colorectal cancer progression.

Original languageEnglish
Pages (from-to)2471-2479
Number of pages9
JournalInternational Journal of Cancer
Volume141
Issue number12
DOIs
Publication statusPublished - 2017 Dec 15
Externally publishedYes

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Keywords

  • calcium
  • calcium sensing receptor
  • colorectal cancer
  • molecular pathological epidemiology
  • progression
  • prospective cohorts
  • survival

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Momen-Heravi, F., Masugi, Y., Qian, Z. R., Nishihara, R., Liu, L., Smith-Warner, S. A., Keum, N. N., Zhang, L., Tchrakian, N., Nowak, J. A., Yang, W., Ma, Y., Bowden, M., da Silva, A., Wang, M., Fuchs, C. S., Meyerhardt, J. A., Ng, K., Wu, K., ... Zhang, X. (2017). Tumor expression of calcium sensing receptor and colorectal cancer survival: Results from the nurses’ health study and health professionals follow-up study. International Journal of Cancer, 141(12), 2471-2479. https://doi.org/10.1002/ijc.31021