To our knowledge, no previous study has prospectively evaluated the associations of calcium intake with incident adenoma, metachronous adenoma, and incident cancer in the same cohort using the same food frequency questionnaire, which minimises misclassification that can occur when combining dietary estimates from multiple studies with different food frequency questionnaire instruments. One weakness is that the PLCO is a sigmoidoscopy-based randomised trial, which only screened the distal colorectal region. Thus, incident adenoma cases mainly included adenomas from the left side of the bowel although metachronous adenoma and incident CRC cases included cases from both proximal and distal regions. However, it is interesting that reports found that colonoscopy was linked to reduced deaths from the distal colorectal region, but not the right. 41,42 Similarly another report from the PLCO observed sigmoidoscopic screenings only reduced distal, but not proximal CRC mortality. 25 Further, sigmoidoscopic screenings also significantly reduced both distal and proximal CRC incidence in the PLCO. 25 Thus, the PLCO provides a unique opportunity to test whether calcium intake confers additional protection against proximal and distal CRC among those receiving sigmoidoscopic screening(s). Similar to other nutritional epidemiological studies using food frequency questionnaires, there are possibly non-differential measurement errors which usually bias the results to the null. In addition, despite the relatively large sample sizes in our study, our investigations between calcium intake and colorectal carcinogenesis were constrained when evaluating by Ca:Mg ratio strata. The number of cases for some sub-categories of calcium intake in the <1.7 Ca:Mg ratio stratum were few and in some instances zero, making inferences relating to trends difficult in this stratum. Furthermore, to maintain relatively balanced number of cases in calcium categories in the largest Ca:Mg ratio stratum, we choose 2.5, the median in the data set, as one of the Ca:Mg ratio cut-offs, instead of 2.6 as investigated in previous studies. Finally, considering investigation of three main outcomes, several sub-group analyses and tests for effect modification, it is possible that findings reported in this study may be due to chance. We found different calcium intake distribution between intervention arm and control arm shown in Supplementary Table 1. The reason is not clear, and it may be due to different food frequency questionnaires were in two arms. However, we found the association pattern between calcium intake and CRC risk is similar in the intervention arm and control arm.
The outcome from our research have been in arrangement with some in past times had written studies, however in conflict with people. Each other cohort degree and you will earlier intervention products found large calcium intake or supplementation try regarding meagerly reduced risks of adenoma, metachronous adenoma and you may CRC. seven,8,9,10,11,a dozen,15,thirty-two not, the outcome regarding a massive-level randomised clinical trial (WHI) do not assistance an aftereffect of calcium as well as supplement D supplementation for the occurrence off CRC immediately after seven many years of pursue-right up. sixteen You will be able your pursue-upwards several months during the WHI may not have become long enough to possess a safety impact getting evident. Actually, the analysis of the Nurses’ Fitness Investigation and you may Medical researchers Realize-up Research just exhibited an inverse relationship between calcium supplements consumption and you will CRC also indicated that new connections turned increasingly stronger which have growing attacks from latency, and you may are most effective toward twelve–16 many years go after-upwards period. 33 That have an average follow-upwards months a whole lot more along these lines studies compared to WHI, we too report similar point quotes as the Zhang mais aussi al., that have a stronger inverse relationship having distal CRC but not for proximal CRC. 33 A pooled-studies away from 10 cohort degree as well as stated the new inverse organization anywhere between whole milk and CRC try limited by malignant tumors of the distal, perhaps not the brand new proximal colon. 15 Thus accumulating research constantly suggests calcium supplements consumption was of this reduced chance of distal CRC.
It’s notable if we evaluated this new joint contacts regarding Ca consumption having Milligrams consumption classified from the RDA top for a few different types of colorectal neoplasia chance (experience adenoma, incident CRC otherwise experience distal CRC), we located comparable trends like in the top analyses where in fact the inverse relationships to own California consumption when it comes to this type of outcomes was indeed the healthier getting Mg consumption at the or above the RDA compared to Mg intake less than new RDA (Additional Tables cuatro–6). However, none of tests for communications was statistically extreme conversely towards the tests to possess interaction we observed into California:Milligrams ratios. This really is consistent with past results in the East Western populations into the that the relations was basically statistically high between Ca:Mg percentages that have calcium supplements consumption, yet not between magnesium intake which have calcium supplements intake. 19 This means that, the newest communication having Ca:Mg rates can’t be explained from the magnesium intake alone.