Affordable Access

Access to the full text

Calcium intake and colon cancer risk subtypes by tumor molecular characteristics

Authors
  • Keum, NaNa1, 2
  • Liu, Li1, 3, 4
  • Hamada, Tsuyoshi3
  • Qian, Zhi Rong3
  • Nowak, Jonathan A.5
  • Cao, Yin6
  • da Silva, Annacarolina3
  • Kosumi, Keisuke3
  • Song, Mingyang1, 7, 8
  • Nevo, Daniel9, 10
  • Wang, Molin9, 10
  • Chan, Andrew T.7, 8, 11
  • Meyerhardt, Jeffrey A.3
  • Fuchs, Charles S.12, 13, 14
  • Wu, Kana1
  • Ogino, Shuji1, 3, 5, 10, 15
  • Nishihara, Reiko1, 3, 5, 9, 10
  • Zhang, Xuehong11
  • 1 Harvard T.H. Chan School of Public Health, Department of Nutrition, Building 2, 3rd Floor, 665 Huntington Avenue, Boston, MA, 02115, USA , Boston (United States)
  • 2 Dongguk University, Department of Food Science and Biotechnology, Goyang, South Korea , Goyang (South Korea)
  • 3 Dana-Farber Cancer Institute and Harvard Medical School, Department of Oncologic Pathology, Boston, MA, USA , Boston (United States)
  • 4 Huazhong University of Science and Technology, Department of Epidemiology and Biostatistics, and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Wuhan, Hubei, People’s Republic of China , Wuhan (China)
  • 5 Brigham and Women’s Hospital and Harvard Medical School, Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Boston, MA, USA , Boston (United States)
  • 6 Washington University School of Medicine, Division of Public Health Sciences, Department of Surgery, St. Louis, MO, USA , St. Louis (United States)
  • 7 Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA , Boston (United States)
  • 8 Massachusetts General Hospital, Division of Gastroenterology, Boston, MA, USA , Boston (United States)
  • 9 Harvard T.H. Chan School of Public Health, Department of Biostatistics, Boston, MA, USA , Boston (United States)
  • 10 Harvard T.H. Chan School of Public Health, Department of Epidemiology, Boston, MA, USA , Boston (United States)
  • 11 Brigham and Women’s Hospital and Harvard Medical School, Channing Division of Network Medicine, Department of Medicine, Boston, MA, USA , Boston (United States)
  • 12 Yale Cancer Center, New Haven, CT, USA , New Haven (United States)
  • 13 Yale School of Medicine, Department of Medicine, New Haven, CT, USA , New Haven (United States)
  • 14 Smilow Cancer Hospital, New Haven, CT, USA , New Haven (United States)
  • 15 Broad Institute of MIT and Harvard, Cambridge, MA, USA , Cambridge (United States)
Type
Published Article
Journal
Cancer Causes & Control
Publisher
Springer-Verlag
Publication Date
Apr 08, 2019
Volume
30
Issue
6
Pages
637–649
Identifiers
DOI: 10.1007/s10552-019-01165-3
Source
Springer Nature
Keywords
License
Yellow

Abstract

BackgroundA preventive potential of high calcium intake against colorectal cancer has been indicated for distal colon cancer, which is inversely associated with high-level CpG island methylator phenotype (CIMP), high-level microsatellite instability (MSI), and BRAF and PIK3CA mutations. In addition, BRAF mutation is strongly inversely correlated with KRAS mutation. We hypothesized that the association between calcium intake and colon cancer risk might vary by these molecular features.MethodsWe prospectively followed 88,506 women from the Nurses’ Health Study and 47,733 men from the Health Professionals Follow-up Study for up to 30 years. Duplication-method Cox proportional cause-specific hazards regression was used to estimate multivariable hazard ratios (HRs), and 95% confidence intervals (95% CIs) for the associations between calcium intake and the risk of colon cancer subtypes. By Bonferroni correction, the α-level was adjusted to 0.01.ResultsBased on 853 colon cancer cases, the inverse association between dietary calcium intake and colon cancer risk differed by CIMP status (pheterogeneity = 0.01). Per each 300 mg/day increase in intake, multivariable HRs were 0.84 (95% CI 0.76–0.94) for CIMP-negative/low and 1.12 (95% CI 0.93–1.34) for CIMP-high. Similar differential associations were suggested for MSI subtypes (pheterogeneity = 0.02), with the corresponding HR being 0.86 (95% CI 0.77–0.95) for non-MSI-high and 1.10 (95% CI 0.92–1.32) for MSI-high. No differential associations were observed by BRAF, KRAS, or PIK3CA mutations.ConclusionThe inverse association between dietary calcium intake and colon cancer risk may be specific to CIMP-negative/low and possibly non-MSI-high subtypes.

Report this publication

Statistics

Seen <100 times