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 T0 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 Tstep 3/5 screen which resulted in an endoscopy that discovered recurrence were also included.
Immediately following then restricting to prospects exactly who finished a legitimate BQ (n = 1978), zero cancers records in advance of BQ (n = 1894), complete DQX (n = 1784), a valid DQX (letter = 1742) and you will who had no disease records prior to DQX (letter = 1741), the very last data provided 855 colorectal metachronous adenoma instances and you will 886 controls.
CRC occurrence
More an average pursue-right up chronilogical age of 12.5 years, colorectal cancer chance is actually determined primarily courtesy shipped Yearly Study Revision Questionnaire and you may repeated emailing mennation nedir otherwise phone in the event you didn’t work. Medical suggestions were used to confirm disease incidence, phase and venue. twenty five The brand new input case of your PLCO demo try subsequent minimal so you can a legitimate BQ (n = 75,611), no reputation of any cancer tumors in advance of BQ (letter = 72,151), complete a great DQX (n = sixty,358), has actually good DQX (n = 58,637) with no reputation of people malignant tumors just before DQX (n = 58,535). Brand new handle arm of your own PLCO demo is actually subsequent limited by a legitimate BQ (letter = 74,366), zero history of one malignant tumors prior to BQ (letter = 70,885) and no reputation for one cancer tumors before DHQ (n = 44,934). The very last study incorporated 58,535 sufferers throughout the input arm, of exactly who 697 create CRC throughout go after-upwards. This new manage sleeve are quicker to 49,934 people which have appropriate BQ, DHQ no cancers history, regarding which 578 create CRC throughout the go after-up.
Mathematical investigation
Realization analytics both for persisted (imply ± practical deviation) and you will categorical details (amount and you will %) were utilized to spell it out data populations. Person-decades to possess CRC incidence is determined regarding time of randomisation to your big date regarding CRC medical diagnosis, death, loss-to-follow-upwards, otherwise avoid out-of pursue-right up, any sort of showed up first. twenty-five
Since information on incident and metachronous adenoma was only collected 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).