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 guyspy 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 results from our analysis are in contract with some in earlier times blogged education, in conflict with others. Each other cohort knowledge and before intervention samples located high calcium intake or supplementation is related to modestly reduced risks of adenoma, metachronous adenoma and you can CRC. 7,8,9,10,eleven,a dozen,15,thirty two But not, the outcomes of a big-level randomised clinical trial (WHI) do not assistance an effect of calcium also vitamin D supplementation toward occurrence away from CRC immediately after 7 years of realize-up. sixteen It’s possible the follow-up period in the WHI may not have already been for a lengthy period to possess a defensive impression as evident. Actually, the investigation of the Nurses’ Wellness Data and Health care professionals Realize-right up Investigation not merely exhibited a keen inverse relationship anywhere between calcium intake and you may CRC also showed that new connections turned into progressively more powerful which have increasing episodes away from latency, and you may try most powerful with the twelve–sixteen ages realize-upwards period. 33 Which have the typical go after-upwards months so much more similar to this research compared to WHI, i as well statement comparable section prices because the Zhang et al., with a healthier inverse relationship to possess distal CRC yet not for proximal CRC. 33 Good pooled-investigation regarding ten cohort studies together with advertised the latest inverse association between whole milk and you may CRC are limited to malignant tumors of your own distal, perhaps not the new proximal anus. fifteen Hence accumulating proof continuously ways calcium supplements intake are of the less chance of distal CRC.
Metachronous colorectal adenoma (perennial adenoma)
It is notable whenever i analyzed new combined connectivity off Ca consumption having Mg intake categorised by the RDA level for a few different kinds of colorectal neoplasia exposure (experience adenoma, event CRC or incident distal CRC), we discover comparable manner as in our number 1 analyses where the inverse relationships for Ca consumption when it comes to such consequences was indeed all of the healthier to possess Mg consumption during the otherwise over the RDA opposed to Milligrams intake less than this new RDA (Second Tables 4–6). not, nothing of one’s tests to own interaction have been statistically significant conversely for the tests to own telecommunications we observed into the Ca:Milligrams ratios. This is exactly consistent with past results in Eastern Western populations inside that your relations was in fact mathematically tall anywhere between Ca:Milligrams percentages having calcium supplements consumption, although not between magnesium consumption having calcium consumption. 19 Simply put, the new communications that have Ca:Milligrams ratios can’t be informed me of the magnesium consumption by yourself.