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 T3/5 screen which resulted in an endoscopy that discovered recurrence were also included.
Shortly after subsequent restricting to people which accomplished a legitimate BQ (n = 1978), zero cancer tumors record before BQ (letter = 1894), done DQX (n = 1784), a valid DQX (letter = 1742) and you can that has zero malignant tumors records prior to DQX (letter = 1741), the very last data included 855 colorectal metachronous adenoma circumstances and you will 886 controls.
CRC occurrence
More an average follow-right up chronilogical age of several.five years, colorectal disease occurrence is actually ascertained mainly thanks to mailed Yearly Investigation Revise Questionnaire and you may regular mailing or cellphone in the event you don’t act. Medical details were utilized to verify cancer tumors chance, stage and you will venue. twenty-five The fresh new intervention case of your own PLCO demonstration try next restricted to help you a legitimate BQ (n = 75,611), zero reputation for people disease just before BQ (letter = 72,151), finished good DQX (n = sixty,358), has good DQX (n = 58,637) without reputation of people cancer tumors just before DQX (letter = 58,535). The fresh control arm of PLCO trial was subsequent limited to a legitimate BQ (n = 74,366), no history of people cancers in advance of BQ (n = 70,885) without reputation of people malignant tumors in advance of DHQ (n = forty-two,934). The past 
studies incorporated 58,535 sufferers throughout the input arm, off who 697 arranged CRC during follow-upwards. The brand new control sleeve are shorter in order to forty-two,934 people that have good BQ, DHQ and no malignant tumors history, off exactly who 578 arranged CRC throughout the pursue-right up.
Statistical studies
Summation analytics for both continuing (imply ± simple departure) and you may categorical parameters (number and you can %) were used to describe study communities. Person-years to possess CRC incidence try determined regarding the big date away from randomisation for the go out out-of CRC analysis, passing, loss-to-follow-right up, otherwise stop out of realize-up, almost any appeared very first. 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 ( 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).
