Participants with a positive baseline FSG screening, diagnostic endoscopy within 6 months from baseline and no cancer findings were invited to complete the interviewer-administered telephone-based Study of Colonoscopy Utilization (SCU) questionnaire. 26 A baseline adenoma was defined as an adenoma found within the first 18 months following a positive T_{0 0} FSG screen, or on an endoscopy within 6 months of the first endoscopy following the screen. A questionnaire collected information on all known endoscopy after randomisation. Medical record abstraction was performed to verify the collected questionnaire information. Individuals with diagnosed adenoma at baseline but free of adenoma at the second endoscopy were considered controls for this analysis, while individuals with a diagnosis of adenoma at the second endoscopy after resection of adenoma found at baseline were defined as recurrent colorectal adenoma cases. Participants not in SCU but with a positive T_3/5 screen which resulted in an endoscopy that discovered recurrence were also included.

Shortly after next limiting to people which done a legitimate BQ (n = 1978), no cancer tumors record ahead of BQ (n = 1894), done DQX (n = 1784), a valid DQX (letter = 1742) and you may who had no cancer tumors history ahead of DQX (n = 1741), the final investigation provided 855 colorectal metachronous adenoma instances and 886 control.

CRC occurrence

More than an average realize-right up chronilogical age of twelve.5 years, colorectal cancer occurrence was determined primarily by way of mailed Annual Research Up-date Questionnaire and you may frequent emailing otherwise phone just in case you failed to function. Medical records were utilized to verify malignant tumors occurrence, phase and you may location. twenty-five The fresh input case of the PLCO demo try further restricted to a legitimate BQ (letter = 75,611), no reputation for one cancer in advance of BQ (n = 72,151), done a good DQX (letter = sixty,358), keeps valid DQX (letter = 58,637) and no history of any cancer tumors before DQX (n = 58,535). The fresh manage case of one’s PLCO trial was after that simply for a legitimate BQ (letter = 74,366), zero reputation for people cancer tumors ahead of BQ (n = 70,885) with no reputation for any disease in advance of DHQ (n = 44,934). The past data provided 58,535 sufferers about input sleeve, regarding exactly who 697 set up CRC during follow-upwards. The latest manage arm is shorter to forty two,934 players that have valid BQ, DHQ and no cancers history, regarding which 578 establish CRC while in the go after-up.

Statistical analysis

Bottom line analytics for both persisted (indicate ± simple deviation) and you can categorical details (matter and percent) were used to spell it out investigation populations. Person-many years to own CRC chance was determined in the time of randomisation on the time regarding CRC analysis, demise, loss-to-follow-upwards, or avoid out of realize-right up, any sort of arrived earliest. 25

Since information on incident and metachronous adenoma was only collected fastflirting hesabД±m yasaklandД± and confirmed after the T₃ or T₅ screen, we estimated 5-year risks for incident and metachronous adenomas with odds ratios and corresponding 95% confidence intervals (95% CIs) calculated using multivariable adjusted unconditional logistic regression. Risk for incident CRC was estimated using hazard ratios and corresponding 95% CIs from multivariable adjusted cox-proportional hazard models. Potential confounding factors were selected based on biological plausibility, literature reports and/or ?10% change in relative risks. 27 Confounding factors evaluated included age, sex, race, education, recruitment site, family history of CRC, body mass index, smoking status, alcohol consumption, exercise and daily intakes of total energy, vitamin D and magnesium. Tests for trend across categories were performed in regression models by assigning the score j to the jth level of the variable selected.

For primary analysis, calcium intake was categorised as 600 mg/day, 600–1200 mg/day, 1200–1600 mg/day and ?1600 mg/day. Previous studies showed a protective effect of calcium in risk reduction at daily intake levels of calcium from 600 to 1000 mg/day, 28 with no further protection beyond this range. 15,29,30 Almost all participants in our study are 50 years or older. The calcium RDA is 1200 mg/day for women between 51 and 70 years and for all adults aged > 70 years. 31 Thus, 600–1200 mg/day is used as the reference group. The cut-off at 1600 mg/day is the upper quartile in this study. Investigation of associations between calcium intake and all three outcomes were also conducted by strata of Ca:Mg ratios (<1.7, 1.7–2.5 and ?2.5). Multiplicative interactions between calcium and the Ca:Mg ratio in relation to the three outcomes were formally tested using the likelihood ratio test or Wald test, where both variables, calcium and the Ca:Mg ratio, were treated as continuous variables for maximal power. To better evaluate the robustness of observed associations, several sensitivity and sub-group analyses were performed. For incident adenoma, in addition to evaluating adenoma of any size, sub-analyses were performed to evaluate associations with advanced/synchronous adenomas. For metachronous adenoma and CRC incidence in the intervention arm, analyses were stratified on baseline adenoma characteristics (e.g., advanced and/or synchronous adenoma). For CRC, analyses were performed by location of cancer: distal vs. proximal, and by clinical trial assignment: intervention arm vs. control arm. Finally, associations between calcium intake and the three outcomes were modelled as joint categories of Ca intake and magnesium intake as defined by the Recommended Dietary Allowance (RDA) (below RDA; at or above RDA). RDA for magnesium is 320 and 420 mg for women and men, respectively while RDA for calcium aged > 50 is 1200 and 1000 mg for women and men, respectively. All tests were two-sided, and statistical significance threshold was set at 0.05. Statistical analyses were performed using SAS statistical software (version 9.4; SAS Institute, Cary, NC).