Metachronous colorectal adenoma (recurrent adenoma)
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 investigation can be found in agreement with many before published training, in dispute with others. Each other cohort degree and you will prior to intervention products discovered high calcium supplements intake otherwise supplements is actually associated with moderately shorter dangers of adenoma, metachronous adenoma and you may CRC. seven,8,9,ten,11,several,15,thirty two not, the results away from a huge-measure randomised clinical trial (WHI) don’t service an effectation of calcium supplements as well as supplement D supplements to the chance of CRC once 7 many years of go after-upwards. 16 You will be able that follow-right up period in WHI might not have started for enough time having a defensive impact getting apparent. In fact, the analysis of the Nurses’ Health Study and you can Health professionals Follow-right up Study not merely demonstrated a keen inverse relationship between calcium supplements intake and you her hesap silme will CRC and revealed that the new associations turned into progressively more powerful with increasing symptoms away from latency, and you will is actually most powerful into a dozen–16 ages realize-up months. 33 Which have the average go after-right up period a great deal more like this investigation compared to the WHI, we as well declaration equivalent section rates because Zhang mais aussi al., that have a stronger inverse relationship having distal CRC not to own proximal CRC. 33 A good pooled-study from ten cohort studies as well as advertised brand new inverse connection anywhere between dairy and you will CRC are restricted to cancer tumors of distal, maybe not the fresh proximal anus. fifteen For this reason accumulating research continuously indicates calcium supplements consumption was associated with quicker danger of distal CRC.
It’s significant if we analyzed this new shared connections from Ca consumption that have Mg consumption classified by the RDA level for a few different kinds of colorectal neoplasia risk (event adenoma, event CRC or experience distal CRC), we receive equivalent trends as in the top analyses where inverse connections getting Ca consumption when it comes to this type of effects was all stronger to have Milligrams consumption during the otherwise over the RDA opposed so you’re able to Milligrams intake lower than the fresh new RDA (Additional Dining tables cuatro–6). However, none of evaluating to possess communication was indeed statistically tall on the other hand on the assessment getting communication we noticed towards the Ca:Mg ratios. This can be consistent with earlier conclusions in the Eastern Far eastern populations during the which the interactions was indeed mathematically significant anywhere between Ca:Milligrams percentages that have calcium intake, however anywhere between magnesium intake with calcium intake. 19 This basically means, the new communications which have Ca:Milligrams rates can’t be said by the magnesium intake by yourself.