Median plasma adiponectin was lower in case subjects vs control subjects in the full population (6.2 vs 6.8 µg/mL, P = .009), among men (4.6 vs 5.3 µg/mL, P = .006), and among women (7.4 vs 7.8 µg/mL, P = .07). Adiponectin levels were comparable across studies for men (HPFS and PHS I) and for women (NHS, WHI, and WHS). Among case subjects, median plasma adiponectin was 4.8 µg/mL (10th–90th percentile = 2.4–8.0) for HPFS, 4.4 µg/mL (10th–90th percentile = 2.2–10.3) for PHS I, 6.9 µg/mL (10th–90th percentile = 3.3–17.3) for NHS, 7.8 µg/mL (10th–90th percentile = 3.4–16.3) for WHI, and 6.4 µg/mL (10th–90th percentile = 3.5–14.6) for WHS. Among control subjects, median plasma adiponectin was 5.2 µg/mL (10th–90th percentile = 2.6–10.4) for HPFS, 5.3 µg/mL (10th–90th percentile = 2.9–9.2) for PHS I, 7.7 µg/mL (10th–90th percentile = 3.8–14.2) for NHS, 8.2 µg/mL (10th–90th percentile = 3.8–16.8) for WHI, and 7.1 µg/mL (10th–90th percentile = 4.5–11.0) for WHS. Individuals in the upper quintiles of adiponectin were less likely to have diabetes, more likely to use multivitamins, and had lower BMI and C-peptide levels ().
Age- and study-standardized baseline characteristics according to plasma adiponectin levels among control subjects*
We observed a statistically significant inverse association between plasma adiponectin and risk of pancreatic cancer. In the base model conditioned on matching factors, compared with the lowest quintile of plasma adiponectin, individuals in quintiles 2 to 5 experienced odds ratios of 0.60 (95% CI = 0.43 to 0.85), 0.57 (95% CI = 0.41 to 0.80), 0.55 (95% CI = 0.38 to 0.78), and 0.60 (95% CI = 0.42 to 0.86), respectively, and the P value for trend was .004 (). Further adjustment for race, multivitamin use, plasma 25(OH)D, diabetes, BMI, physical activity, and plasma C-peptide yielded similar results. Compared with the lowest quintile of circulating adiponectin, individuals in quintiles 2 to 5 had multivariable odds ratios of 0.61 (95% CI = 0.43 to 0.86), 0.58 (95% CI = 0.41 to 0.84), 0.59 (95% CI = 0.40 to 0.87), and 0.66 (95% CI = 0.44 to 0.97), respectively (P
trend = .04) ().
Odds ratios and 95% confidence intervals for pancreatic cancer according to quintiles of plasma adiponectin
We also performed separate analyses in men and women using gender-specific quartiles and observed similar inverse associations. Odds ratios for quartiles 2 to 4 were 0.76 (95% CI = 0.42 to 1.36), 0.66 (95% CI = 0.36 to 1.21), and 0.60 (95% CI = 0.32 to 1.12) for men (P
trend = .08) and 0.66 (95% CI = 0.45 to 0.96), 0.76 (95% CI = 0.51 to 1.13), and 0.78 (95% CI = 0.51 to 1.19) for women (P
trend = .30). There was no statistically significant heterogeneity due to sex (P = .36).
The restricted cubic splines showed a pattern similar to the quintile analysis (, ); the multivariable odds ratio declined dramatically with increasing levels of adiponectin to approximately 5 µg/mL, but then flattened out (P for nonlinearity < .01). Similar patterns were observed among men and women, when analyzed separately (, and ). Thus for subsequent subgroup analyses, we categorized adiponectin by combining quintiles 2 to 5. The multivariable odds ratio comparing less than 4.4 µg/mL vs 4.4 µg/mL or greater was 0.62 (95% CI = 0.47 to 0.82) for the full population, 0.55 (95% CI = 0.35 to 0.86) for men, and 0.65 (95% CI = 0.45 to 0.95) for women ().
Figure 1. Nonparametric regression curve for the association between plasma adiponectin and risk of pancreatic cancer. A) Full population. B) Men. C) Women. Multivariable odds ratios were calculated by restricted cubic spline conditional logistic model. Odds ratios (more ...)
Multivariable-adjusted odds ratios and 95% confidence intervals for pancreatic cancer by plasma adiponectin, among subgroups*
Furthermore, we observed similar odds ratios when analyzing each cohort separately (), with no statistically significant heterogeneity across studies (P = .49). We conducted a meta-analysis to pool the cohort-specific odds ratios. Comparing less than 4.4 µg/mL vs 4.4 µg/mL or greater, the summary odds ratio of 0.62 (95% CI = 0.45 to 0.83) obtained by pooling the cohort-specific odds ratios () was the same as the odds ratio obtained by pooling the primary data from the five cohorts.
Figure 2. Cohort-specific and meta-analysis pooled odds ratios (ORs) of pancreatic cancer according to dichotomized plasma adiponectin levels (<4.4 vs ≥4.4 µg/mL). Cohort-specific multivariable odds ratios are conditioned on the matching (more ...)
Similar odds ratios were observed comparing less than 4.4 µg/mL vs 4.4 µg/mL or greater when we excluded case subjects diagnosed within 2 years (multivariable OR = 0.60; 95% CI = 0.45 to 0.80) or 4 years (multivariable OR = 0.53; 95% CI = 0.38 to 0.74) from the date of blood draw or limited the analysis to nondiabetics (multivariable OR = 0.62; 95% CI = 0.46 to 0.82). No statistically significant interaction of plasma adiponectin and pancreatic cancer risk was seen for other potential risk factors for pancreatic cancer, including sex, age at blood draw, follow-up time of case subjects, fasting time, smoking status, BMI, physical activity, and C-peptide levels (P > .10 for all) (), and higher adiponectin remained inversely related to risk of pancreatic cancer across all subgroups ().