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Context: Inflammation may play a role in the pathogenesis of colorectal cancer; however, epidemiological evidence supporting this hypothesis in average-risk persons is sparse., Objective: To determine the risk of incident colon and rectal cancer associated with elevated baseline plasma concentrations of C-reactive protein (CRP)., Design, Setting, and Participants: Prospective, nested case-control study of a cohort of 22 887 adults (>18 years and Washington County, Maryland, residents) enrolled between May and October 1989 and followed up through December 2000. A total of 172 colorectal cancer cases were identified through linkage with the Washington County and Maryland State Cancer registries. Up to 2 controls (n = 342) were selected from the cohort for each case and matched by age, sex, race, and date of blood draw., Main Outcome Measure: Odds ratio (OR) of incident colon and rectal cancer., Results: Plasma CRP concentrations were higher among all colorectal cases combined than controls (median CRP, 2.44 vs 1.94 mg/L; P =.01). The highest concentration was found in persons who subsequently developed colon cancer vs matched controls (median CRP, 2.69 vs 1.97 mg/L; P<.001). Among rectal cancer cases, CRP concentrations were not significantly different from controls (median CRP, 1.79 vs 1.81 mg/L; P =.32). The risk of colon cancer was higher in persons in the highest vs lowest quartile of CRP (OR, 2.55; 95% confidence interval [CI], 1.34-4.88; P for trend =.002). In nonsmokers, the corresponding association was stronger (OR, 3.51; 95% CI, 1.64-7.51; P for trend<.001). A 1-SD increase in log CRP (1.02 mg/L) was associated with an increased risk of colon cancer after adjusting for potential confounders and excluding cases occurring within 2 years of baseline (OR, 1.35; 95% CI, 1.05-1.74) or excluding those with late-stage colon cancer at the time of diagnosis (OR, 1.38; 95% CI, 0.99-1.91)., Conclusions: Plasma CRP concentrations are elevated among persons who subsequently develop colon cancer. These data support the hypothesis that inflammation is a risk factor for the development of colon cancer in average-risk individuals.

Objective: To prospectively examine the association between endogenous hormones and development of ovarian cancer., Design: Nested case-control study., Setting: A population-based serum bank in Washington County, Maryland., Participants: Serum samples were collected in 1974 from 20305 county residents and stored at -70 degrees C. From 1975 through 1989, a total of 31 cases of ovarian cancer were identified in women who were not taking hormones at the time of blood collection. These cases were matched to 62 controls on age, menopausal status, and, for premenopausal women, number of days from the beginning of the last menstrual period., Main Outcome Measure: Prediagnostic endogenous hormone levels of cases and controls were compared., Results: Mean follicle-stimulating hormone levels were lower among cases (43.3 IU/L) compared with controls (54.4 IU/L) (P = .04), and increasing levels were associated with significantly lower risk (P for trend = .01), particularly among postmenopausal women. Luteinizing hormone levels were 9% lower among cases than controls, but the difference was not statistically significant (P = .39). Compared with controls, cases had higher androstenedione levels (4.5 nmol/L vs 3.3 nmol; P = .03) and higher dehydroepiandrosterone (DHEA) levels (15.9 nmol/L vs 9.7 nmol/L; P = .02). The risk of ovarian cancer increased with higher levels of androstenedione and DHEA sulfate (P for trend = .008 and .11, respectively). These associations were not materially different between premenopausal and postmenopausal women., Conclusion: The results suggest that women with low serum gonadotropin levels or high androgen levels have an increased risk of ovarian cancer. These findings do not support the hypothesis that pituitary gonadotropins increase the risk of ovarian cancer. Replication of the study in other populations is highly desirable.

Objective: To evaluate prospectively the sensitivity and specificity of serum CA-125 levels for the detection of ovarian cancer., Design: Case-control study nested within a cohort of women who donated blood to a community-based serum bank established in 1974., Setting: Washington County, Maryland., Population: Cases consisted of 37 women who developed ovarian cancer from 1975 through 1989. Controls consisted of 73 women, matched on age and time since last menstrual period, and free of cancer until the cases' diagnoses. STUDY VARIABLE: Serum CA-125 levels., Outcome Measure: Histologically confirmed ovarian cancer., Results: Levels of serum CA-125 among cases were higher than among controls for each 3-year interval up to 12 years prior to the time of the cases' diagnoses. The median level for cases diagnosed within the first 3 years of follow-up was 35.4 U/mL compared with 9.0 U/mL for controls (P = .002). The sensitivity of a serum CA-125 level greater than 35 U/mL within the first 3 years was 57% (95% confidence interval, 20% to 88%) and the specificity was 100% (95% confidence interval lower limit, 73%). Sensitivity and specificity decreased with increasing time to diagnosis., Conclusions: Measurement of serum CA-125 levels, particularly at a reference value of 35 U/mL, is not sufficiently sensitive to be used alone as a screening test for the detection of ovarian cancer. Lower CA-125 reference values could identify women at higher risk of developing ovarian cancer, but CA-125 measurement cannot be recommended for this purpose because of the high proportion of women who would be falsely classified as being at high risk for developing ovarian cancer.