Society: AGA

BACKGROUND
Early-onset colorectal cancer (CRC diagnosed before age 50) has risen worldwide, with an increasing number of survivors of reproductive age. We aimed to investigate the risk of adverse pregnancy and neonatal outcomes among early-onset CRC survivors.

METHODS
We conducted a nationwide study of 207 births in women with early-onset CRC and 1019 births in women without CRC from the general Swedish population (1992-2019), matched on age, calendar year, parity, and county of residence. To further adjust for confounding, we identified 146 births in female siblings of women with early-onset. Early-onset CRC cases were identified through the Swedish Cancer Register. Sibling identification and outcome data were retrieved through linkage of the Swedish Multi-generation Register, Medical Birth Register, and National Patient Register. Using conditional logistic regression, we estimated multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs).

RESULTS
Compared to women without prior CRC, early-onset CRC survivors who gave birth had increased risk of pre-eclampsia (7.2% vs 3.2%; OR=2.52, 95%CI 1.25-5.08), any Cesarean delivery (C-section) (24.6% vs 19.4%; OR=1.43, 95%CI 1.00-2.06), particularly emergency C-section (17.4% vs 10.5%; OR=1.79, 95%CI 1.17-2.75), after adjustment for maternal education level, country of birth, body mass index and smoking in early pregnancy, and comorbidities. Sibling analyses showed similar trends. Maternal history of early-onset CRC was also associated with offspring preterm birth (12.1% vs 5.2%; OR=2.31, 95%CI 1.34-3.99), delineated as spontaneous (OR=1.06, 95%CI 0.47-2.39) or medically-indicated preterm birth (OR=4.48, 95%CI 2.05-9.79). There was no increased risk of congenital malformation or small for gestational age birth.

CONCLUSIONS
In this population-based study, maternal history of early-onset CRC was associated with risk of both adverse pregnancy (pre-eclampsia, C-section) and neonatal outcomes (preterm birth).

BACKGROUND & AIMS
Substantial geographic variability in gastrointestinal (GI) cancer mortality has been reported in the United States. There is a substantial variation in the socioeconomic, ethnic composition, and social infrastructure among US counties. Whether underlying variation in social vulnerabilities among counties influence GI cancer mortality is uncertain. The aim of this study was to examine the association between county-level social vulnerability and GI cancer mortality.

METHODS
In this cross-sectional study in the US (2014-2020), we linked county-level Social Vulnerability Index (SVI) with county-level age-adjusted GI cancer mortality. SVI comprised of four subcomponents (socioeconomic status; household composition and disability; minority status and language; and housing type and transportation) and was created using 15 social attributes. We categorized SVI into quintiles based on the distribution among US counties (1^st [least vulnerable] to 5^th [most vulnerable]). We used generalized estimating equation to estimate the age-adjusted GI cancer mortality and rate ratio (RR) by quintiles of SVI. We examined mortality for all GI cancers and five individual GI cancers (esophageal cancer, gastric cancer, liver cancer, pancreatic cancer, and colorectal cancer). We adjusted for lifestyle factors in multivariable models including obesity, smoking, physical activity, alcohol consumption, and diet.

RESULTS
There were 1,101,223 GI cancer deaths from 2014 to 2020 among a population of 2,267,748,585. The largest concentration of counties with more social vulnerabilities and higher GI cancer mortality were clustered across the southwestern and southeastern parts of the US (Figure). The age-adjusted mortality rates per 100,000 population (95% CI) for all GI cancers, esophageal cancer, gastric cancer, liver cancer, pancreatic cancer, and colorectal cancer were 42.5 (42.0-43.0), 4.3 (4.1-4.4), 3.0 (2.9-3.1), 7.1 (6.9-7.2), 11.6 (11.4-11.7), and 15.3 (15.0-15.6) (Table). There was an increase in overall GI cancer mortality with higher SVI (RR_{Q5 vs Q1}, 1.22; 95% CI, 1.19-1.26). This was also observed in all individual GI cancer types (RR_{Q5 vs Q1} ranging from 1.08 to 1.63). After adjusting for lifestyle factors, only gastric cancer (RR_{Q5 vs Q1}, 1.46; 95% CI, 1.33-1.59) and liver cancer mortality (RR_{Q5 vs Q1}, 1.31; 95% CI, 1.20-1.43) remained significantly associated with SVI.

CONCLUSIONS
In this analysis, US counties with more social vulnerabilities had higher GI cancer mortality, some of which could be attributed to disparities in lifestyle risk factors. Focused public health interventions should be directed to counties with higher social vulnerability to curb the growing burden of GI cancer.

<b>Figure. Social Vulnerability Index (2014–2018) and GI cancer mortality rates (2014–2020) in the US. </b>(A) Counties by Social Vulnerability Index; (B) by age-adjusted GI cancer mortality rates. Q indicates quintile.

Figure. Social Vulnerability Index (2014–2018) and GI cancer mortality rates (2014–2020) in the US. (A) Counties by Social Vulnerability Index; (B) by age-adjusted GI cancer mortality rates. Q indicates quintile.

<b>Table. Association between Social Vulnerability Index and age-adjusted mortality rates for GI cancer, 2014-2020</b>

Table. Association between Social Vulnerability Index and age-adjusted mortality rates for GI cancer, 2014-2020

Introduction: Incidence rates of colorectal cancer (CRC) are increasing in younger (age 18-49 years) and middle-age (age 50-59 years) adults in the U.S. Rates have increased by birth cohort, a phenomenon that informed recommendations to lower the age to initiate average-risk screening. This birth cohort effect has not yet been examined in other parts of the world. To address this gap, we conducted an age-period-cohort analysis to test for birth cohort effects in seven world regions.

Methods: We used data from the Global Health Data Exchange to identify adults (age 20-89 years) newly diagnosed with CRC during 1990 – 2019 in seven world regions: East Asia, Europe and Central Asia, Latin America and the Caribbean, the Middle East and North Africa, North America, South Asia, and Sub-Saharan Africa. The Global Health Data Exchange comprises 204 countries and territories and uses data from vital registration, verbal autopsy, and population-based cancer registries to generate estimates of incident cancers. We used five-year age groups (e.g., 20-24) and time periods (e.g., 1990-94) to create 17 birth cohorts (1910-14 to 1990-94). Separately by region, we estimated the ratio of age-specific incidence rates of CRC in each birth cohort relative to the 1950-54 birth cohort. We report incidence rate ratios (IRR) and 95% confidence intervals (CI).

Results: Age-specific incidence rates of CRC increased across birth cohorts after 1950-54 in all regions of the world, with the exception of Europe and Central Asia. Compared to persons born in 1950-54, incidence rates of CRC were up to two times as high among persons born in the 1980s and 90s (Image). This pattern was more prominent in East Asia, Latin America and the Caribbean, and the Middle East and North Africa, but less so in Sub-Saharan Africa. For example, in East Asia, IRRs were 1.98 (95% CI 1.85, 2.13) and 2.53 (95% CI 2.23, 2.87) for the 1980-84 and 1990-94 birth cohorts, respectively. There were small increases for persons born in or after 1955-59 in Sub-Saharan Africa, with IRRs ranging from 1.03 (95% CI 1.02, 1.04) for the 1955-59 birth cohort to 1.16 (95% CI 1.11, 1.21) for the 1990-94 birth cohort. There was no increase by birth cohort in Europe and Central Asia.

Discussion: In nearly all regions of the word, incidence rates of CRC have increased among persons born after 1950-54, with particularly notable increases in East Asia, Latin America and the Caribbean, and the Middle East and North Africa. These increases occurred despite differences in the age structure, screening programs, diet and lifestyle, and diagnostic factors among world regions. Identifying environmental exposures introduced in and increasingly prevalent after 1950 (e.g., pesticides, flame retardants) may hold the key to finding risk factors responsible.

Timothy Zaki

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