ObjectiveFactors that lead to metabolic dysregulation are associated with increased risk of early-onset colorectal cancer (CRC diagnosed under age 50). However, the association between metabolic syndrome (MetS) and early-onset CRC remains unexamined.DesignWe conducted a nested case–control study among participants aged 18–64 in the IBM MarketScan Commercial Database (2006–2015). Incident CRC was identified using pathologist-coded International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes, and controls were frequency matched. MetS was defined as presence of ≥3 conditions among obesity, hypertension, hyperlipidaemia and hyperglycaemia/type 2 diabetes, based on ICD-9-CM and use of medications. Multivariable logistic regressions were used to estimate ORs and 95% CIs.ResultsMetS was associated with increased risk of early-onset CRC (n=4673; multivariable adjusted OR 1.25; 95% CI 1.09 to 1.43), similar to CRC diagnosed at age 50–64 (n=14 928; OR 1.21; 95% CI 1.15 to 1.27). Compared with individuals without a metabolic comorbid condition, those with 1, 2 or ≥3 conditions had a 9% (1.09; 95% CI 1.00 to 1.17), 12% (1.12; 95% CI 1.01 to 1.24) and 31% (1.31; 95% CI 1.13 to 1.51) higher risk of early-onset CRC (ptrend <0.001). No associations were observed for one or two metabolic comorbid conditions and CRC diagnosed at age 50–64. These positive associations were driven by proximal (OR per condition 1.14; 95% CI 1.06 to 1.23) and distal colon cancer (OR 1.09; 95% CI 1.00 to 1.18), but not rectal cancer (OR 1.03; 95% CI 0.97 to 1.09).ConclusionsMetabolic dysregulation was associated with increased risk of early-onset CRC, driven by proximal and distal colon cancer, thus at least in part contribute to the rising incidence of early-onset CRC.

1571 Background: The etiology and contributors to the rising incidence of early-onset colorectal cancer (CRC diagnosed under age 50), driven largely by distal and rectal cancer, remain largely unknown. Metabolic syndrome is associated with higher risk of CRC diagnosed at older ages; however, its association with early-onset CRC remains unclear. Methods: We conducted a nested case-control study among participants aged 18-50 years with ≥2 years of enrollment and prescription drug coverage in the IBM MarketScan Commercial Databases (2006-2015). Incident CRC cases were identified using ICD-9-CM diagnosis codes. Controls without any cancer were identified using frequency matching on age, sex, geographical region, and duration of insurance enrollment. Metabolic syndrome was defined using either ICD-9-CM diagnosis codes or the presence of at least 3 of the following: obesity, hypertension, hyperlipidemia, and hyperglycemia/type 2 diabetes. In addition to ICD-9-CM codes, hypertension, hyperlipidemia, and hyperglycemia/type 2 diabetes were also defined based on regular use of medications. Multivariable logistic regressions were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results: A total of 4,673 early-onset CRC and 40,832 controls were included. Metabolic syndrome was associated with increased risk of early-onset CRC (OR: 1.33, 95% CI 1.16-1.52), after adjusting for a range of potential confounders. The number of metabolic comorbid conditions was positively associated with risk of early-onset CRC in a dose-response fashion. Compared to individuals without any conditions, individuals with 1, 2, ≥3 metabolic conditions had a 13% (OR: 1.13, CI 1.04-1.22), 18% (OR: 1.18, CI 1.07-1.31), and 40% (OR: 1.40, CI 1.22-1.61) higher risk of early-onset CRC (Ptrend<0.001), respectively. These associations were driven by proximal (OR for ≥2 vs 0 metabolic comorbid conditions: 1.40, CI 1.15-1.69) and distal colon cancer, OR ≥2 vs 0: 1.25, CI 1.03-1.53), but not rectal cancer (OR≥2 vs 0: 1.07, CI 0.92-1.24). Conclusions: Metabolic syndrome and metabolic comorbid conditions were associated with increased risk of early-onset CRC, largely driven by proximal and distal colon cancer. Metabolic dysregulations may contribute to the rising incidence of early-onset CRC.

To examine the association between statemandated insurance coverage for infertility treatment in the United States and the utilization of and indication for preimplantation genetic testing. METHODS:This was a retrospective cohort study of 301,465 in vitro fertilization (IVF) cycles reported to the Society for Assisted Reproductive Technology between 2014 and 2016. Binomial logistic regression was performed to examine associations between state-mandated insurance coverage and preimplantation genetic testing use. The neonate's sex from each patient's first successful cycle was used to calculate sex ratios. Sex ratios then were compared by state mandates and preimplantation genetic testing indication for elective sex selection.