Cardiovascular Risks Associated With Celecoxib and Rofecoxib Dose/Drugs continued...
The 2011 analysis examined data from eight RCTs, seven of which provided individual patient data and three of which provided 20-year follow-up data. In trials with allocation to ASA of at least 5 years, the 20-year HR for CRC mortality was 0.60 (95% CI, 0.45–0.81). Six RCTs, including five from the United Kingdom, were included in a meta-analysis in which patients were randomly assigned to receive either aspirin or placebo and mean scheduled duration of trial treatment was 4 years or more. Individual patient data for all in-trial cancer deaths were obtained. In the three United Kingdom trials, cancer deaths after completion of the trials were obtained via death certification and cancer registration, taking the follow-up to 20 years after randomization. Based on meta-analysis of odds ratios from each trial rather than on more sensitive actuarial analysis of the individual patient data, allocation to aspirin in the RCTs reduced the 20-year risk of death due to colorectal (and esophageal) cancer. Odds ratios for 'maximum aspirin use' were 0.55 for colorectal cancer risk (95% CI, 0.41–0.76) and 0.47 for esophageal cancer risk (95% CI, 0.27–0.81) and for 'any aspirin use' were 0.58 for colorectal cancer risk (95% CI, 0.44–0.78) and 0.51 for esophageal cancer (95% CI, 0.31–0.83).
In a large cohort study, an association between recent daily aspirin use and lower-cancer mortality in the gastrointestinal tract (RR = 0.61; 95% CI, 0.47–0.78), liver (RR = 0.52; 95% CI, 0.30–0.93), and bladder (RR = 0.52; 95% CI, 0.28–0.97) were observed among the 100,139 analysis-eligible participants from the Cancer Prevention Study II Nutrition Cohort established by the American Cancer Society in 1982. The analysis excluded participants who had a history of cancer in the baseline year or whose records contained incomplete information on aspirin use or smoking, and was based on follow-up questionnaires mailed to participants in 1997 (the baseline year for the analysis), 1999, 2001, and 2003. Mortality follow-up continued through Dec 31, 2008 via automated linkage to the National Death Index vital status and cause of death codes (ICD-10); death certificates were obtained for 99.3% of known deaths.
Postmenopausal female hormone supplements
Several observational studies have suggested a decreased risk of colon cancer among users of postmenopausal female hormone supplements.[66,67,68,69] For rectal cancer, most studies have observed no association or a slightly elevated risk.[70,71,72]
In the Women's Health Initiative (WHI) Trial, 16,608 postmenopausal women aged 50 to 79 years were randomly assigned to a combination of conjugated equine estrogens (0.625 mg/day) plus medroxyprogesterone (2.5 mg/day) or placebo. There were 43 invasive CRCs in the hormone group and 72 in the placebo group (HR = 0.56; 95% CI, 0.38–0.81; P = .003). The invasive CRCs in the hormone group were similar in histologic features and grade to those in the placebo group but with a greater number of positive lymph nodes (mean ± standard deviation 3.24 ± 4.1 vs. 0.8 ± 1.7; P = .002) and were more advanced (regional or metastatic disease; 76.2% vs. 48.5%; P = .004).