shows the mean values and distributions of the variables of interest at approximately the midpoint of the follow-up period (1990). presents results from our final model. Women who reported a family history of colon or rectal cancer had a statistically significantly increased risk; we found a 55% increased risk of colon cancer (relative risk (RR) = e0.4383 = 1.55) among persons who had at least 1 first-degree relative diagnosed with colon or rectal cancer.
Distribution of Selected Risk Factors in the Nurses’ Health Study, 1990
Beta Coefficients Derived From a Fitted Model of Colon Cancer Incidence and Associated Relative Risks of Colon Cancer (n = 701 cases), Nurses’ Health Study, 1980–2004
Current use of postmenopausal hormones was associated with a statistically significant 23% reduction in risk of colon cancer (RR = e−0.2625 = 0.77). Although past users had an overall 2% decreased risk, the effect was much weaker than that for current use and was essentially null (RR = e−0.0228 = 0.98).
Measures of energy balance were supportive of previous findings. Specifically, height was positively associated with increased risk. Compared with a 61-inch-tall (155-cm) woman, a 67-inch-tall (170-cm) woman had a 19% increased risk (RR = e(0.000736)(6)(40) = 1.19). Body mass index was suggestive of a positive association; for a body mass index of 30 compared with a body mass index of 20, there was a 16% increased risk (RR = e(0.000373)(10)(40) = 1.16). Physical activity showed an expected inverse association, which was statistically significant. Women who engaged in physical activity at a level of 21 MET-hours/week for 40 years had a 49% reduction in risk compared with women who only had 2 MET-hours of activity per week (RR = e(−0.00089)(19)(40) = 0.51; , part A).
Figure 1. Age-specific incidence of colon cancer per 100,000 person-years for A) a woman with 2 metabolic equivalent (MET)-hours/week of physical activity and a woman who reported 21 MET-hours/week of physical activity from age 30 years to age 70 years; B) a woman (more ...)
Intake of red and processed meat was associated with an increased risk. A woman who consumed 1 serving of red or processed meat daily for 40 years had a 20% increased risk of colon cancer compared with a woman who did not eat any red or processed meat (RR = e(0.00452)40 = 1.20; , part B). Women who consumed 600 μg/day of folate for 40 years had a modest 16% reduction in risk compared with women who had a folate intake of 150 μg/day (RR = e(−9.76E-06)(450)(40) = 0.84).
Smoking increased risk for colon cancer; women who accrued 10 pack-years of smoking before the age of 30 years had a 16% increased risk compared with nonsmokers (RR = e(0.000368)(10)(40) = 1.16). , part C, shows the age-specific incidence rates for a woman who had 10 pack-years of smoking before age 30 years as compared with the same age-specific rates for a never smoker.
Screening (by endoscopy) was associated with a significantly reduced risk. A woman who was screened from age 50 years to age 70 years had a 24% reduced risk of developing colon cancer. Lastly, we confirmed that aspirin has an important inverse association with colon cancer risk. The use of 7 aspirin tablets per week for 40 years (1 tablet per day) was associated with a 29% reduction in risk (RR = e(−0.00122)(7)(40) = 0.71; , part D).
In order to evaluate the influence of screening on the natural history of the disease, we also censored women who were diagnosed with adenoma during the follow-up period (on the date of their adenoma diagnosis). For this analysis, we had 631 cases accumulated over 1,588,035 person-years. The results were essentially the same as the main results from the full model with screening as a covariate (data not shown).
After choosing the variables in our final model (), we used the coefficients to generate age-specific incidence rates from age 30 years to age 70 years. Using the age-specific incidence rates, we then estimated the cumulative incidence of colon cancer up to age 70 years for hypothetical women with varying levels of specific risk factors, holding the other variables constant (). Increased risk was observed for height, having a consistently high relative body weight from age 18 years to age 70 years, having a family history of colon or rectal cancer, and smoking before age 30 years. Important inverse associations were observed for current postmenopausal hormone use, being consistently lean, being physically active, taking aspirin, and being screened by endoscopy. Although the overall association with body mass index was not statistically significant (), a lifetime pattern of overweight was associated with increased risk. Given the same average height of 64 inches (163 cm), women who were consistently lean (at the 10th age-specific percentile from age 18 years to age 70 years; 105 pounds (48 kg) at age 18, 118 pounds (54 kg) at age 50, 120 pounds (55 kg) at age 60, and 118 pounds (54 kg) at age 70) had a 7% reduced risk of colon cancer (95% confidence interval (CI): −1%, −13%) compared with the “average” woman in this cohort (a weight of 123 pounds (56 kg) at age 18, 142 pounds (65 kg) at age 50, 146 pounds (66 kg) at age 60, and 145 pounds (66 kg) at age 70). More strikingly, a woman who had a consistently high relative body weight (at the 90th age-specific percentile; 150 pounds (68 kg) at age 18, 185 pounds (84 kg) at age 50, 190 pounds (86 kg) at age 60, and 185 pounds (84 kg) at age 70) had a 68% increased risk (95% CI: 39%, 103%) compared with a woman of “average” weight and height.
Table 3. Comparative Effects of Different Colon Cancer Risk Factors on Cumulative Incidence of Colon Cancer From Age 30 Years to Age 70 Years and Associated Relative Risks of Colon Cancer Obtained Using a Model Based on the Nurses’ Health Study, 1980–2004 (more ...)
To evaluate the combined effect of multiple modifiable risk factors, we compared women with various risk factor profiles, keeping the other (nonmodifiable) variables constant. Women with a moderate risk profile had an elevated and statistically significant 44% increased risk compared with the low-risk group (RR = 1.44, 95% CI: 1.05, 1.96). Women with a high risk factor profile (women who smoked, had a consistently high relative weight, had a low physical activity level, consumed 1 serving per day of red or processed meat, were never screened, and consumed low amounts of folate (150 μg/day)) had a 3.8-fold increased risk (RR = 3.84, 95% CI: 1.61, 9.16; and ). We observed a slightly stronger effect of aspirin use for high-risk women versus moderate-risk women when compared with women at low risk (). Lastly, we evaluated the effect of screening among high-risk women (). Although endoscopic screening from age 50 years to age 70 years reduced the risk among high-risk women, their risk was still much higher than that of women whose lifestyle behaviors placed them in the moderate- or low-risk category.
Figure 2. Age-specific incidence of colon cancer per 100,000 person-years from age 30 years to age 70 years for 1) a “high-risk” participant (one who accrued 10 pack-years of smoking before age 30 years, had a consistently high relative body weight, (more ...)
Figure 3. Age-specific incidence of colon cancer per 100,000 person-years from age 30 years to age 70 years, according to aspirin use, for 1) a “high-risk” participant (one who accrued 10 pack-years of smoking before age 30 years, had a consistently (more ...)
Figure 4. Age-specific incidence of colon cancer per 100,000 person-years from age 30 years to age 70 years, according to screening behavior, for 1) a high-risk” participant (one who accrued 10 pack-years of smoking before age 30 years, had a consistently (more ...)
We evaluated the predictive ability of our log-incidence model using receiver operating characteristic (ROC) curve analysis. First, we calculated the predicted absolute risk of colon cancer for each woman using all of the risk factors in our final model and stratified the data by 5-year age group. Within each age group, we then calculated the Mann-Whitney U
statistic, thus obtaining an index that can be interpreted as the probability that within a specific 5-year age group a random case will have a higher predicted risk than a random noncase or, alternatively, as the area under the ROC curve based on our predicted model for women in a specific age group. We then computed a weighted average of the age-specific Mann-Whitney U
statistics with weights equal to the inverse variance of the age-specific statistics. Overall, the area under the ROC curve, adjusted for age, was 0.61 (95% CI: 0.59, 0.63). This is consistent with other published reports on the discriminatory accuracy of breast and ovarian cancer models (19, 20), as well as a recent colon cancer model developed by Park et al. (21
) and Freedman et al. (22