Table 3.
Odds ratio for colorectal cancer by mutation status of BRAF or PIK3CA according to plasma adiponectin level in the Nurses’ Health Study and the Health Professionals Follow-up Study
| Colorectal cancer subtype | Tertile 3 | Tertile 2 | Tertile 1 | P trend* | P heterogeneity† |
|---|---|---|---|---|---|
| Women (NHS) | |||||
| BRAF wild-type | |||||
| No. of case patients/control individuals (121/236) | 29/73 | 40/84 | 52/79 | ||
| Age-adjusted OR (95% CI)‡ | 1 (referent) | 1.23 (0.69 to 2.17) | 1.84 (0.99 to 3.43) | .06 | |
| Multivariable-adjusted OR (95% CI)§ | 1 (referent) | 1.19 (0.63 to 2.25) | 1.76 (0.89 to 3.49) | .12 | |
| BRAF-mutant | |||||
| No. of case patients/control individuals (30/59) | 14/20 | 6/17 | 10/22 | ||
| Age-adjusted OR (95% CI)‡ | 1 (referent) | 0.55 (0.19 to 1.63) | 0.69 (0.26 to 1.87) | .40 | |
| Multivariable-adjusted OR (95% CI)§ | 1 (referent) | 0.52 (0.15 to 1.74) | 0.54 (0.17 to 1.74) | .26 | .07 |
| PIK3CA wild-type | |||||
| No. of case patients/control individuals (123/239) | 31/73 | 38/75 | 54/91 | ||
| Age-adjusted OR (95% CI)‡ | 1 (referent) | 1.16 (0.67 to 2.03) | 1.47 (0.83 to 2.61) | .20 | |
| Multivariable-adjusted OR (95% CI)§ | 1 (referent) | 1.16 (0.62 to 2.16) | 1.37 (0.71 to 2.63) | .37 | |
| PIK3CA-mutant | |||||
| No. of case patients/control individuals (20/40) | 9/14 | 5/18 | 6/8 | ||
| Age-adjusted OR (95% CI)‡ | 1 (referent) | 0.43 (0.10 to 1.81) | 0.90 (0.20 to 4.08) | .94 | |
| Multivariable-adjusted OR (95% CI)§ | 1 (referent) | 0.35 (0.07 to 1.71) | 0.74 (0.15 to 3.67) | .78 | .54 |
| Men (HPFS) | |||||
| BRAF wild-type | |||||
| No. of case patients/control individuals (142/270) | 38/95 | 50/89 | 54/86 | ||
| Age-adjusted OR (95% CI)‡ | 1 (referent) | 1.44 (0.85 to 2.43) | 1.76 (1.00 to 3.08) | .05 | |
| Multivariable-adjusted OR (95% CI)§ | 1 (referent) | 1.43 (0.79 to 2.61) | 1.90 (0.98 to 3.67) | .06 | |
| BRAF-mutant | |||||
| No. of case patients/control individuals (13/26) | 4/9 | 3/5 | 6/12 | ||
| Age-adjusted OR (95% CI) ‡ | 1 (referent) | 1.46 (0.18 to 11.8) | 1.19 (0.23 to 6.13) | .87 | |
| Multivariable-adjusted OR (95% CI)§ | 1 (referent) | 1.06 (0.12 to 9.58) | 0.91 (0.15 to 5.52) | .91 | .44 |
| PIK3CA wild-type | |||||
| No. of case patients/control individuals (117/224) | 33/82 | 40/68 | 44/74 | ||
| Age-adjusted OR (95% CI)‡ | 1 (referent) | 1.52 (0.83 to 2.76) | 1.65 (0.89 to 3.05) | .10 | |
| Multivariable-adjusted OR (95% CI)§ | 1 (referent) | 1.55 (0.80 to 3.03) | 1.70 (0.84 to 3.43) | .13 | |
| PIK3CA-mutant | |||||
| No. of case patients/control individuals (28/53) | 6/19 | 12/19 | 10/15 | ||
| Age-adjusted OR (95% CI)‡ | 1 (referent) | 1.96 (0.62 to 6.23) | 2.17 (0.60 to 7.78) | .20 | |
| Multivariable-adjusted OR (95% CI)§ | 1 (referent) | 1.62 (0.40 to 6.66) | 3.11 (0.64 to 15.1) | .17 | .52 |
| Combined (women [NHS] and men [HPFS]) | |||||
| BRAF wild-type | |||||
| No. of case patients/control individuals (263/506) | 67/168 | 90/173 | 106/165 | ||
| Age-adjusted OR (95% CI)‡ | 1 (referent) | 1.33 (0.91 to 1.97) | 1.79 (1.18 to 2.72) | .007 | |
| Multivariable-adjusted OR (95% CI)§ | 1 (referent) | 1.41 (0.93 to 2.13) | 1.81 (1.15 to 2.83) | .01 | |
| BRAF-mutant | |||||
| No. of case patients/control individuals (43/85) | 18/29 | 9/22 | 16/34 | ||
| Age-adjusted OR (95% CI)‡ | 1 (referent) | 0.67 (0.26 to 1.73) | 0.77 (0.34 to 1.79) | .49 | |
| Multivariable-adjusted OR (95% CI)§ | 1 (referent) | 0.60 (0.22 to 1.63) | 0.53 (0.21 to 1.33) | .15 | .01 |
| PIK3CA wild-type | |||||
| No. of case patients/control individuals (240/463) | 64/155 | 78/143 | 98/165 | ||
| Age-adjusted OR (95% CI)‡ | 1 (referent) | 1.32 (0.88 to 1.98) | 1.55 (1.02 to 2.35) | .04 | |
| Multivariable-adjusted OR (95% CI)§ | 1 (referent) | 1.40 (0.91 to 2.17) | 1.46 (0.93 to 2.30) | .11 | |
| PIK3CA-mutant | |||||
| No. of case patients/control individuals (48/93) | 15/33 | 17/37 | 16/23 | ||
| Age-adjusted OR (95% CI)‡ | 1 (referent) | 1.06 (0.46 to 2.48) | 1.58 (0.62 to 4.06) | .38 | |
| Multivariable-adjusted OR (95% CI)§ | 1 (referent) | 1.07 (0.42 to 2.72) | 1.89 (0.67 to 5.29) | .28 | .72 |
* Tests for trend (the Wald statistics, two-sided) were conducted using the median values for each tertile of plasma adiponectin. CI = confidence interval; HPFS = Health Professionals Follow-up Study; NHS = Nurses’ Health Study; OR = odds ratio.
† Likelihood ratio tests (two-sided) were used to test for heterogeneity (comparing the associations across tumor subtypes).
‡ Results were based on conditional logistic regression analysis with adjustment for age at blood draw and date of blood collection.
§ Results were based on conditional logistic regression analysis (which accounted for age at blood draw and date of blood collection) with additional adjustment for fasting status (<8 hours, ≥8 hours since last meal), body mass index (continuous, kg/m2), physical activity level (continuous, metabolic equivalent hour per week), family history of colorectal cancer (yes, no), multivitamin use (yes, no), regular aspirin use (yes, no), hormone replacement therapy (yes, no; NHS only), history of previous lower endoscopy (yes, no), pack-years of smoking before 30 years of age (continuous), intake of total calorie (continuous, kcal/day), red meat intake (continuous, serving/day), processed meat intake (continuous, serving/day), calcium intake (continuous, mg/day), folate intake (continuous, μg/day), alcohol consumption (continuous, g/day), and plasma 25-hydroxyvitamin D (tertile, ng/mL). The median (range) levels of plasma adiponectin across tertiles among controls are the same as shown in Table 2.