Dutch Study Points to Low Risk of Gastric, Duodenal Cancers in Those Under 50 Years of Age

Lynch syndrome, a form of hereditary colorectal cancer, may also increase the risk of gastric cancer (GC) and duodenal cancer (DC) in individuals with MLH1 and MSH2 pathogenic variants (PVs).

A new nationwide cohort study led by Irene Caspers, MD, PhD, and colleagues evaluated the most beneficial time to carry out esophagogastroduodenoscopy (EGD) surveillance by researching the incidence and tumor characteristics of GC and DC in a cohort of Dutch patients with Lynch syndrome.

Researchers matched the clinical data of patients with Lynch syndrome who were registered at the Dutch Hereditary Cancer Registry with pathology reports filed by the Dutch Pathology Registry.

Eligible patients included in the study were registered between January 1989 and December 2021 and had proven PVs in one of the mismatch repair genes. The cumulative incidence rates of GC and DC were estimated for those with high-risk (MLH1, MSH2, and EpCAM) and low-risk (MSH6 and PMS2) PVs using competing risk methodology (Fine and Gray method). Death due to other causes was a competing risk.

A total of 1002 individuals had high-risk PVs and 29 (1.6%) GC cases diagnosed, while 765 had low-risk PVs and 39 (2.2%) DC cases diagnosed. Individuals under the age of 50 had a very low (≤1%) risk of GC and DC.

The median cumulative incidence of GC in individuals aged 70 and 75 years was 3% (95% CI, 1%-5%) and 5% (3%-8%) for high-risk PVs and 1% (0%-2%) and 1% (0%-2%) for low-risk PVs (P=.006), respectively. For individuals aged 70 and 75 years with DC, the median cumulative incidence was 5% (95% CI, 3%-7%) and 6% (3%-8%) for high-risk PVs and 1% (0%-1%) and 2% (0%-4%) for low-risk PVs, respectively (P=.01).

Primary tumor resection was performed in 62% (18/29) of patients with GC and 77% (30/39) of those with DC. Early-stage GC, defined as TNM stage I, was found in 32% (9/28) of patients with GC. Early-stage DC, defined as TNM stage I-IIa, was found in 39% (14/36) of those with DC.

Individuals with MLH1, MSH2, and EpCAM PVs were found to have a higher risk of developing GC and DC at the age of 70 years, with a very low risk of occurrence before the age of 50 years. Further studies are warranted to analyze potential correlations between the age of surveillance onset and occurrence of GC and DC during EGD surveillance.