Table 3.

Combined effect of past OC use and risk genotypes (ONECUT2 rs4092465 GA; HNF4A rs1800961 TT) on CRC risk overall and in BMI strata

n£	Risk genotype + past OC use
	Total n	HR† (95% CI)	p *
	<Overall group>
0	3,559	reference
1	4,949	4.40 (3.32-5.83)	< 2e-16
2	1,634	17.54 (13.22-23.28)	< 2e-16
p trend			< 2e-16
	<Non-overall obese group, BMI < 30 kg/m2 (n=7,151)>
0	2,594	reference
1	3,501	4.23 (3.08-5.82)	< 2e-16
2	1,056	17.41 (12.62-24.02)	< 2e-16
p trend			< 2e-16
	<Overall obese group, BMI ≥ 30 kg/m2 (n=2,991)>
0	965	reference
1	1,448	5.08 (2.77-9.30)	1.37e-07
2	578	19.96 (10.91-36.51)	< 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.

^£The combined number of risk genotypes and behavioral factors was based on 1) risk genotypes defined as 0 (low risk: none or 1 risk allele) and 1 (high risk: 2 risk alleles) and 2) behavioral factors defined as 0 (low risk: past OC use ≥ 5.1 years) and 1 (high risk: past OC use < 5.1 years).

The ultimate number of combined risk genotypes and behavioral factors was defined as 0 (low risk for genotypes and behaviors), 1 (high risk for either genotypes or behaviors), and 2 (high risk for both genotypes and behaviors).

^†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, and exogenous estrogen plus progestin.

^* p values were adjusted to correct for multiple testing via the Benjamini-Hochberg approach.