Table 4.
Joint effect of past OC use with risk genotypes (ONECUT2 rs4092465 GA; HNF4A rs1800961 TT) on CRC risk overall and in BMI strata
| n | Total | Past OC use ≥ 5.1 years | Past OC use < 5.1 years | |||||
|---|---|---|---|---|---|---|---|---|
|
|
|
|
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| HR† (95% CI) | p* | n | HR† (95% CI) | p * | n | HR† (95% CI) | p * | |
| <Overall group> | ||||||||
| Risk genotypes£ | ||||||||
| 0 | reference | 3,559 | reference | 1,492 | 1.59 (1.04-2.43) | 0.03415 | ||
| 1 | 7.39 (5.93-9.20) | < 2e-16 | 3,457 | 5.46 (4.11-7.25) | < 2e-16 | 1,634 | 17.15 (12.92-22.76) | < 2e-16 |
| p trend | < 2e-16 | |||||||
| <Non-overall obese group, BMI < 30 kg/m2 (n=7,151)> | ||||||||
| Risk genotypes£ | ||||||||
| 0 | reference | 2,594 | reference | 946 | 1.52 (0.92-2.53) | 0.10148 | ||
| 1 | 7.07 (5.48-9.12) | < 2e-16 | 2,555 | 5.14 (3.73-7.07) | < 2e-16 | 1,056 | 17.05 (12.36-23.53) | < 2e-16 |
| p trend | < 2e-16 | |||||||
| <Overall obese group, BMI ≥ 30 kg/m2 (n=2,991)> | ||||||||
| Risk genotypes£ | ||||||||
| 0 | reference | 965 | reference | 546 | 1.89 (0.83-4.30) | 0.12766 | ||
| 1 | 8.40 (5.43-12.97) | < 2e-16 | 902 | 6.69 (3.64-12.31) | 1e-09 | 578 | 19.50 (10.66-35.68) | < 2e-16 |
| p trend | < 2e-16 | |||||||
BMI, body mass index; CI, confidence interval; CRC, colorectal cancer; HR, hazard ratio; OC, oral contraceptive. Numbers in bold face are statistically significant.
Multivariate regression was adjusted by age at enrollment, education, BMI (in overall group), height and weight (in BMI strata), waist-to-hip ratio, age at menopause, total months of breastfeeding, OC use (in total analysis), and exogenous estrogen plus progestin.
p values were adjusted to correct for multiple testing via the Benjamini-Hochberg approach.
The number of risk genotypes was defined on the basis of Kaplan-Meier analysis as follows: 0 (none or 1 risk allele) and 1 (2 risk alleles).