TY - JOUR
T1 - Tumor expression of calcium sensing receptor and colorectal cancer survival
T2 - Results from the nurses’ health study and health professionals follow-up study
AU - Momen-Heravi, Fatemeh
AU - Masugi, Yohei
AU - Qian, Zhi Rong
AU - Nishihara, Reiko
AU - Liu, Li
AU - Smith-Warner, Stephanie A.
AU - Keum, Na Na
AU - Zhang, Lanjing
AU - Tchrakian, Nairi
AU - Nowak, Jonathan A.
AU - Yang, Wanshui
AU - Ma, Yanan
AU - Bowden, Michaela
AU - da Silva, Annacarolina
AU - Wang, Molin
AU - Fuchs, Charles S.
AU - Meyerhardt, Jeffrey A.
AU - Ng, Kimmie
AU - Wu, Kana
AU - Giovannucci, Edward
AU - Ogino, Shuji
AU - Zhang, Xuehong
N1 - Publisher Copyright:
© 2017 UICC
PY - 2017/12/15
Y1 - 2017/12/15
N2 - 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.
AB - 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.
KW - calcium
KW - calcium sensing receptor
KW - colorectal cancer
KW - molecular pathological epidemiology
KW - progression
KW - prospective cohorts
KW - survival
UR - http://www.scopus.com/inward/record.url?scp=85030174396&partnerID=8YFLogxK
U2 - 10.1002/ijc.31021
DO - 10.1002/ijc.31021
M3 - Article
C2 - 28856682
AN - SCOPUS:85030174396
SN - 0020-7136
VL - 141
SP - 2471
EP - 2479
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 12
ER -