Calcium intake and risk of colorectal cancer according to expression status of calcium-sensing receptor (CASR)
Year: 2017
Type: article
Abstract: Objective Although evidence suggests an inverse association between calcium intake and the risk of colorectal cancer, the mechanisms remain unclear. The calcium-sensing receptor (CASR) is expressed abundantly in normal colonic epithelium and may influence carcinogenesis. We hypothesized that calcium intake might be associated with lower risk of CASR-positive, but not CASR-negative, colorectal cancer. Design We assessed tumour CASR protein expression using immunohistochemistry in 779 incident colon and rectal cancer cases that developed among 136 249 individuals in the Nurses’ Health Study and Health Professionals Follow-Up Study. Duplication method Cox proportional hazards regression analysis was used to assess associations of calcium intake with incidence of colorectal adenocarcinoma subtypes by CASR status. Results Total calcium intake was inversely associated with the risk of developing colorectal cancer (ptrend=0.01, comparing ≥1200 vs <600 mg/day: multivariable HR=0.75, 95% CI 0.60 to 0.95). For the same comparison, higher total calcium intake was associated with a lower risk of CASR-positive tumours (ptrend=0.003, multivariable HR=0.67, 95% CI 0.51 to 0.86) but not with CASR-negative tumours (ptrend=0.67, multivariable HR=1.15, 95% CI 0.75 to 1.78; pheterogeneity=0.06 between the CASR subtypes). The stronger inverse associations of calcium intake with CASR-positive but not CASR-negative tumours generally appeared consistent regardless of sex, tumour location and source of calcium. Conclusions Our molecular pathological epidemiology data suggest a causal relationship between higher calcium intake and lower colorectal cancer risk, and a potential role of CASR in mediating antineoplastic effect of calcium.
Source: Gut
Authors: Wanshui Yang, Li Liu, Yohei Masugi, Zhi Rong Qian, Reiko Nishihara, NaNa Keum, Kana Wu, Stephanie Smith-Warner, Yanan Ma, Jonathan A Nowak, Fatemeh Momen-Heravi, Libin Zhang, Michaela Bowden, Teppei Morikawa, Annacarolina da Silva, Molin Wang, Andrew T Chan, Charles S Fuchs, Jeffrey A Meyerhardt, Kimmie Ng, Edward Giovannucci, Shuji Ogino, Xuehong Zhang
Institutions: Jiujiang University, Harvard University, Dana-Farber Cancer Institute, Dana-Farber/Harvard Cancer Center, Huazhong University of Science and Technology, Brigham and Women's Hospital, Dongguk University, China Medical University, Columbia University, University of Massachusetts Boston, Institute for Community Inclusion, The University of Tokyo, Massachusetts General Hospital, Yale Cancer Center, Yale University, Smilow Cancer Hospital
Language: English
Topic: Vitamin D Research Studies
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Dana Farber/ Harvard Cancer Center SPORE in Gastrointestinal Cancer, Calcium and Colorectal Cancer: Gene-Environment Interactions and Molecular Pathways, Epigenetic Events and Colorectal Cancer Epidemiology, Dietary And Lifestyle Determinants Of Colon Cancer Recurrence and Survival, Inflammation and Colorectal Neoplasia, Accelerating Transdisciplinary Epidemiology of Colorectal Cancer, Dietary and Hormonal Determinants of Cancer in Women, Impact of Celecoxib and Inflammation on Survival in Stage III Colon Cancer, Mentored Patient-Oriented Research in Digestive Diseases, Prospective Studies of Diet and Cancer in Men and Women, Long Term Multidisciplinary Study of Cancer in Women: The Nurses Health Study, Cancer Epidemiology Cohort in Male Health Professionals, Lifestyle, genetics and colonoscopy for colorectal cancer prevention, Calcium Intake and Colorectal Cancer Incidence and Survival, Leveraging Novel Randomized Clinical Trials of Vitamin D Supplementation in Patients with Colorectal Cancer: Impact on Survival and Anti-Tumor Immunity, Yale Clinical and Translational Science Award, Cancer Epidemiology Cohort in Male Health Professionals
OpenAlex ID: W2726791951