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08.04.2019 | Original Paper

Calcium intake and colon cancer risk subtypes by tumor molecular characteristics

Zeitschrift:
Cancer Causes & Control
Autoren:
NaNa Keum, Li Liu, Tsuyoshi Hamada, Zhi Rong Qian, Jonathan A. Nowak, Yin Cao, Annacarolina da Silva, Keisuke Kosumi, Mingyang Song, Daniel Nevo, Molin Wang, Andrew T. Chan, Jeffrey A. Meyerhardt, Charles S. Fuchs, Kana Wu, Shuji Ogino, Reiko Nishihara, Xuehong Zhang
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s10552-019-01165-3) contains supplementary material, which is available to authorized users.
Use of standardized official symbols: We use HUGO (Human Genome Organisation)—approved official symbols for genes and gene products, including BRAF, CASR, KRAS, and PIK3CA; all of which are described at www.​genenames.​org. The official symbols are italicized, to differentiate from nonitalicized colloquial names that are used along with the official symbols. This format enables readers to familiarize the official symbols for genes and gene products together with common colloquial names.
NaNa Keum, Li Liu, and Tsuyoshi Hamada have contributed equally as co-first authors.
Reiko Nishihara, and Xuehong Zhang have contributed equally as co-last authors.

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Abstract

Background

A 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.

Methods

We 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.

Results

Based 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.

Conclusion

The inverse association between dietary calcium intake and colon cancer risk may be specific to CIMP-negative/low and possibly non-MSI-high subtypes.

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Zusatzmaterial
Supplementary material 1 (DOCX 155 kb)
10552_2019_1165_MOESM1_ESM.docx
Literatur
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