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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  

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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