TY - JOUR
T1 - Calcium intake and colon cancer risk subtypes by tumor molecular characteristics
AU - Keum, Na Na
AU - Liu, Li
AU - Hamada, Tsuyoshi
AU - Qian, Zhi Rong
AU - Nowak, Jonathan A.
AU - Cao, Yin
AU - da Silva, Annacarolina
AU - Kosumi, Keisuke
AU - Song, Mingyang
AU - Nevo, Daniel
AU - Wang, Molin
AU - Chan, Andrew T.
AU - Meyerhardt, Jeffrey A.
AU - Fuchs, Charles S.
AU - Wu, Kana
AU - Ogino, Shuji
AU - Nishihara, Reiko
AU - Zhang, Xuehong
N1 - Publisher Copyright:
© 2019, Springer Nature Switzerland AG.
PY - 2019/6/1
Y1 - 2019/6/1
N2 - 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 (p heterogeneity = 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 (p heterogeneity = 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.
AB - 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 (p heterogeneity = 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 (p heterogeneity = 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.
KW - CIMP
KW - Colon cancer
KW - Colorectal cancer
KW - Dietary calcium
KW - MSI
UR - http://www.scopus.com/inward/record.url?scp=85064247356&partnerID=8YFLogxK
U2 - 10.1007/s10552-019-01165-3
DO - 10.1007/s10552-019-01165-3
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AN - SCOPUS:85064247356
SN - 0957-5243
VL - 30
SP - 637
EP - 649
JO - Cancer Causes and Control
JF - Cancer Causes and Control
IS - 6
ER -
