Background

A recent randomized trial found no effect of calcium supplementation on reducing risk of colorectal adenoma recurrence. However, the role of calcium in carcinogenesis is yet unconfirmed. An earlier trial found calcium treatment only reduced recurrence when the baseline calcium: magnesium intake ratio was <2.6. Nor is it clear whether calcium intake is differentially related to risks of different stages of colorectal carcinogenesis (incident adenoma, adenoma recurrence and incident colorectal cancer). Further, it is unclear if calcium intake or supplementation confers additional protection against incident colorectal cancer in individuals receiving endoscopic screenings. To address these important scientific inquiries, we have conducted analyses within the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial.

Methods

The PLCO is a large, multicenter, population-based randomized trial designed to determine the effects of screening on cancer-related mortality with a median of 12.5 years of follow up. We evaluated the associations between calcium intake and the risks of incident colorectal adenoma (1,147 cases), recurrent adenoma (855 cases) and incident colorectal cancer (697 and 578 cases in intervention and control arms, respectively) among 108,563 PLCO participants aged 55 to 74 years. Odds ratios (OR) and 95% confidence intervals (95%CIs) for incident adenoma and recurrent adenoma, and hazard ratios (HR) and 95%CIs for colorectal cancer incidence were calculated using unconditional logistic regression models and Cox proportional hazard models after adjusting covariates.

Results

Compared to low calcium intake (<600 mg/day), higher intakes of calcium were not related to a reduced risk of incidence adenoma, but significantly associated with a reduced risk of advanced/multiple adenomas (p for trend, <0.05). Further, the significant inverse association only appeared when calcium:magnesiuim intake ratios between 1.7 and 2.5. No significant association was observed between Ca intake and risk of adenoma recurrence. In the control arm, we found, compared to low calcium intake, higher intakes of calcium were associated with significantly reduced risks of incident colorectal cancer, primarily distal cancer. Again, we found the inverse association may primarily appear in those with calcium:magnesiuim intake ratios between 1.7 and 2.5. In contrast, in the intervention arm (i.e. screening with flexible sigmoidoscopy), overall, we did not find any significant associations.

Conclusion

Intake of calcium may be more strongly related to reduced risks of incident advanced/multiple adenoma and incident colorectal cancer among those without active screening with flexible sigmoidoscopy than to recurrent adenoma and incident colorectal cancer risks among those with active screening with flexible sigmoidoscopy.

Citation Format: Jing Zhao, Xiangzhu Zhu, Martha J. Shrubsole, Todd L. Edwards, Edward L. Giovannucci, Wei Zheng, Qi Dai, PLCO Project Team. Calcium to magnesium intake ratio and colorectal carcinogenesis, results from the Prostate, Lung, Colorectal, and Ovarian cancer screening trial. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1739.