Tumor expression of calcium sensing receptor and colorectal cancer survival: Results from the nurses' health study and health professionals follow-up study.
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.
['Momen-Heravi|Fatemeh|F|', 'Masugi|Yohei|Y|', 'Qian|Zhi Rong|ZR|', 'Nishihara|Reiko|R|', 'Liu|Li|L|', 'Smith-Warner|Stephanie A|SA|', 'Keum|NaNa|N|0000-0003-4671-0211', 'Zhang|Lanjing|L|', 'Tchrakian|Nairi|N|', 'Nowak|Jonathan A|JA|', 'Yang|Wanshui|W|', 'Ma|Yanan|Y|', 'Bowden|Michaela|M|', 'da Silva|Annacarolina|A|', 'Wang|Molin|M|', 'Fuchs|Charles S|CS|', 'Meyerhardt|Jeffrey A|JA|', 'Ng|Kimmie|K|', 'Wu|Kana|K|', 'Giovannucci|Edward|E|', 'Ogino|Shuji|S|', 'Zhang|Xuehong|X|0000-0002-8260-8508']
D000368:Aged D002423:Cause of Death D015179:Colorectal Neoplasms D019175:DNA Methylation D005260:Female D005500:Follow-Up Studies D015972:Gene Expression Regulation, Neoplastic D006801:Humans D020084:Long Interspersed Nucleotide Elements D008297:Male D053842:Microsatellite Instability D008875:Middle Aged D011379:Prognosis D016016:Proportional Hazards Models D011446:Prospective Studies D044169:Receptors, Calcium-Sensing D016019:Survival Analysis D015854:Up-Regulation
calcium calcium sensing receptor colorectal cancer survival progression molecular pathological epidemiology prospective cohorts