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

Wanshui Yang, Li Liu, Yohei Masugi, Zhi Rong Qian, Reiko Nishihara, Na Na 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 NgEdward Giovannucci, Shuji Ogino, Xuehong Zhang

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
JournalGut
DOIs
Publication statusAccepted/In press - 2017 Jul 4
Externally publishedYes

Fingerprint

Calcium-Sensing Receptors
Colorectal Neoplasms
Calcium
Neoplasms
Molecular Epidemiology
Health
Rectal Neoplasms
Antineoplastic Agents
Colonic Neoplasms
Carcinogenesis
Adenocarcinoma
Epithelium
Immunohistochemistry
Nurses
Regression Analysis

Keywords

  • calcium
  • Calcium-sensing receptor
  • Cancer epidemiology
  • Cancer prevention
  • Cohort study
  • Colon cancer
  • Diet
  • Etiologic heterogeneity
  • Molecular pathological epidemiology
  • Rectal cancer
  • Tumor microenvironment

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Calcium intake and risk of colorectal cancer according to expression status of calcium-sensing receptor (CASR). / Yang, Wanshui; Liu, Li; Masugi, Yohei; Qian, Zhi Rong; Nishihara, Reiko; Keum, Na Na; Wu, Kana; Smith-Warner, Stephanie; Ma, Yanan; Nowak, Jonathan A.; Momen-Heravi, Fatemeh; Zhang, Libin; Bowden, Michaela; Morikawa, Teppei; Silva, Annacarolina da; Wang, Molin; Chan, Andrew T.; Fuchs, Charles S.; Meyerhardt, Jeffrey A.; Ng, Kimmie; Giovannucci, Edward; Ogino, Shuji; Zhang, Xuehong.

In: Gut, 04.07.2017.

Research output: Contribution to journalArticle

Yang, W, Liu, L, Masugi, Y, Qian, ZR, Nishihara, R, Keum, NN, Wu, K, Smith-Warner, S, Ma, Y, Nowak, JA, Momen-Heravi, F, Zhang, L, Bowden, M, Morikawa, T, Silva, AD, Wang, M, Chan, AT, Fuchs, CS, Meyerhardt, JA, Ng, K, Giovannucci, E, Ogino, S & Zhang, X 2017, 'Calcium intake and risk of colorectal cancer according to expression status of calcium-sensing receptor (CASR)', Gut. https://doi.org/10.1136/gutjnl-2017-314163
Yang, Wanshui ; Liu, Li ; Masugi, Yohei ; Qian, Zhi Rong ; Nishihara, Reiko ; Keum, Na Na ; Wu, Kana ; Smith-Warner, Stephanie ; Ma, Yanan ; Nowak, Jonathan A. ; Momen-Heravi, Fatemeh ; Zhang, Libin ; Bowden, Michaela ; Morikawa, Teppei ; Silva, Annacarolina da ; Wang, Molin ; Chan, Andrew T. ; Fuchs, Charles S. ; Meyerhardt, Jeffrey A. ; Ng, Kimmie ; Giovannucci, Edward ; Ogino, Shuji ; Zhang, Xuehong. / Calcium intake and risk of colorectal cancer according to expression status of calcium-sensing receptor (CASR). In: Gut. 2017.
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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.",
keywords = "calcium, Calcium-sensing receptor, Cancer epidemiology, Cancer prevention, Cohort study, Colon cancer, Diet, Etiologic heterogeneity, Molecular pathological epidemiology, Rectal cancer, Tumor microenvironment",
author = "Wanshui Yang and Li Liu and Yohei Masugi and Qian, {Zhi Rong} and Reiko Nishihara and Keum, {Na Na} and Kana Wu and Stephanie Smith-Warner and Yanan Ma and Nowak, {Jonathan A.} and Fatemeh Momen-Heravi and Libin Zhang and Michaela Bowden and Teppei Morikawa and Silva, {Annacarolina da} and Molin Wang and Chan, {Andrew T.} and Fuchs, {Charles S.} and Meyerhardt, {Jeffrey A.} and Kimmie Ng and Edward Giovannucci and Shuji Ogino and Xuehong Zhang",
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TY - JOUR

T1 - Calcium intake and risk of colorectal cancer according to expression status of calcium-sensing receptor (CASR)

AU - Yang, Wanshui

AU - Liu, Li

AU - Masugi, Yohei

AU - Qian, Zhi Rong

AU - Nishihara, Reiko

AU - Keum, Na Na

AU - Wu, Kana

AU - Smith-Warner, Stephanie

AU - Ma, Yanan

AU - Nowak, Jonathan A.

AU - Momen-Heravi, Fatemeh

AU - Zhang, Libin

AU - Bowden, Michaela

AU - Morikawa, Teppei

AU - Silva, Annacarolina da

AU - Wang, Molin

AU - Chan, Andrew T.

AU - Fuchs, Charles S.

AU - Meyerhardt, Jeffrey A.

AU - Ng, Kimmie

AU - Giovannucci, Edward

AU - Ogino, Shuji

AU - Zhang, Xuehong

PY - 2017/7/4

Y1 - 2017/7/4

N2 - 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.

AB - 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.

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KW - Calcium-sensing receptor

KW - Cancer epidemiology

KW - Cancer prevention

KW - Cohort study

KW - Colon cancer

KW - Diet

KW - Etiologic heterogeneity

KW - Molecular pathological epidemiology

KW - Rectal cancer

KW - Tumor microenvironment

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