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 three/5 screen which resulted in an endoscopy that discovered recurrence were also included.
Immediately after then restricting to prospects exactly who done a legitimate BQ (letter = 1978), zero malignant tumors background before BQ (n = 1894), complete DQX (n = 1784), a valid DQX (letter = 1742) and you may who had zero cancer background in advance of https://datingranking.net/de/internationale-datierung/ DQX (n = 1741), the past analysis incorporated 855 colorectal metachronous adenoma times and you will 886 controls.
CRC occurrence
More a median realize-upwards chronilogical age of several.5 years, colorectal cancers chance are determined mainly owing to shipped Annual Studies Revise Questionnaire and you will repeated emailing or mobile in the event you don’t respond. Scientific facts were used to ensure cancers chance, stage and you will area. twenty five This new input case of your PLCO demo is actually then minimal so you can a valid BQ (n = 75,611), zero history of people cancer tumors in advance of BQ (n = 72,151), complete a good DQX (n = sixty,358), features appropriate DQX (letter = 58,637) no history of people cancer tumors before DQX (n = 58,535). The newest manage sleeve of your PLCO demo are after that limited to a legitimate BQ (letter = 74,366), zero reputation of one malignant tumors before BQ (letter = 70,885) with no reputation for people cancers just before DHQ (letter = 49,934). The last analysis incorporated 58,535 victims on the input case, from just who 697 created CRC throughout pursue-up. This new handle arm is actually smaller in order to forty two,934 players with good BQ, DHQ and no cancer record, out of exactly who 578 create CRC during the realize-right up.
Mathematical data
Summation statistics both for persisted (imply ± important deviation) and you may categorical parameters (count and you may percent) were utilized to spell it out analysis populations. Person-decades to have CRC chance are calculated regarding time from randomisation toward go out of CRC diagnosis, passing, loss-to-follow-upwards, otherwise prevent regarding follow-right up, any appeared earliest. 25
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).