Calcium intake and risk of colorectal cancer according to expression status of calcium-sensing receptor (CASR),Gut

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Calcium intake and risk of colorectal cancer according to expression status of calcium-sensing receptor (CASR)
Gut ( IF 23.0 ) Pub Date : 2017-07-04 , DOI: 10.1136/gutjnl-2017-314163
Wanshui Yang ₁ , Li Liu _{2,

3,

4} , Yohei Masugi ₂ , Zhi Rong Qian ₂ , Reiko Nishihara _{2,

3,

5,

6,

7} , NaNa Keum _{3,

8} , Kana Wu ₃ , Stephanie Smith-Warner _{3,

5} , Yanan Ma ₉ , Jonathan A Nowak ₇ , Fatemeh Momen-Heravi _{10,

11} , Libin Zhang ₁₂ , Michaela Bowden ₁₃ , Teppei Morikawa ₁₄ , Annacarolina da Silva ₂ , Molin Wang _{5,

6} , Andrew T Chan _{10,

15,

16} , Charles S Fuchs _{10,

17,

18,

19} , Jeffrey A Meyerhardt ₁₃ , Kimmie Ng ₁₃ , Edward Giovannucci _{3,

5,

10} , Shuji Ogino _{2,

5,

7} , Xuehong Zhang ₁₀

Affiliation

Department of Social Science and Public Health, School of Basic Medical Science, Jiujiang University, Jiujiang, PR China.
Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Department of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA.
Department of Epidemiology and Biostatistics, and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Huazhong University of Science and Technology, Wuhan, PR China.
Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA, USA.
Department of Biostatistics, Harvard TH Chan School of Public Health, Boston, MA, USA.
Department of Pathology, Brigham and Women's Hospital, Division of MPe Molecular Pathological epidemiology, Boston, MA, USA.
Department of Food Science and Biotechnology, Dongguk University, Goyang, South Korea.
Department of Biostatistics and Epidemiology, School of Public Health, China Medical University, Shenyang, PR China.
Department of Medicine, Brigham and Women's Hospital, Channing Division of Network Medicine, Boston, MA, USA.
Section of Oral and Diagnostic Sciences, Division of Periodontics, Columbia University College of Dental Medicine, New York, USA.
University of Massachusetts Boston, Institute for Community Inclusion, Boston, MA, USA.
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Department of Medicine, Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Department of Medical Oncology, Yale Cancer Center, New Haven, CT, USA.
Department of Medicine, Yale School of Medicine, New Haven, CT, USA.
Department of Medical Oncology, Smilow Cancer Hospital, New Haven, CT, USA.

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.

中文翻译：

根据钙敏感受体 (CASR) 表达状态的钙摄入量和结直肠癌风险

目的尽管有证据表明钙摄入量与结直肠癌风险之间存在负相关，但其机制仍不清楚。钙敏感受体（CASR）在正常结肠上皮中大量表达，可能影响癌变。我们假设钙摄入量可能与较低的 CASR 阳性结直肠癌风险相关，但与 CASR 阴性结直肠癌的风险无关。设计我们使用免疫组织化学评估了在护士健康研究和卫生专业人员随访研究中的 136 249 名个体中发生的 779 例结肠癌和直肠癌病例中的肿瘤 CASR 蛋白表达。重复法 Cox 比例风险回归分析用于评估钙摄入量与 CASR 状态下结直肠腺癌亚型发病率的关联。结果总钙摄入量与发生结直肠癌的风险呈负相关（ptrend=0.01，比较≥1200 与 <600 mg/天：多变量 HR=0.75，95% CI 0.60 至 0.95）。对于相同的比较，较高的总钙摄入量与较低的 CASR 阳性肿瘤风险相关（ptrend=0.003，多变量 HR=0.67，95% CI 0.51 至 0.86）但与 CASR 阴性肿瘤无关（ptrend=0.67，多变量HR=1.15, 95% CI 0.75 至 1.78；CASR 亚型之间的异质性=0.06）。无论性别、肿瘤位置和钙来源如何，钙摄入与 CASR 阳性而非 CASR 阴性肿瘤的更强负相关通常似乎是一致的。结论我们的分子病理学流行病学数据表明较高的钙摄入量与较低的结直肠癌风险之间存在因果关系，

更新日期：2017-07-04

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