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Tumor expression of calcium sensing receptor and colorectal cancer survival: Results from the nurses’ health study and health professionals follow‐up study
Author(s) -
MomenHeravi Fatemeh,
Masugi Yohei,
Qian Zhi Rong,
Nishihara Reiko,
Liu Li,
SmithWarner Stephanie A.,
Keum NaNa,
Zhang Lanjing,
Tchrakian Nairi,
Nowak Jonathan A.,
Yang Wanshui,
Ma Yanan,
Bowden Michaela,
da Silva Annacarolina,
Wang Molin,
Fuchs Charles S.,
Meyerhardt Jeffrey A.,
Ng Kimmie,
Wu Kana,
Giovannucci Edward,
Ogino Shuji,
Zhang Xuehong
Publication year - 2017
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.31021
Subject(s) - colorectal cancer , medicine , microsatellite instability , hazard ratio , interquartile range , proportional hazards model , kras , oncology , cancer , confidence interval , biology , allele , biochemistry , microsatellite , gene
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.