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Gastric cancer risk factors in patients with Lynch syndrome identified
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Several clinical factors, including older age and family history, are linked with gastric cancer among individuals with Lynch syndrome-associated mutations, according to study results.
The findings could provide a basis for a risk-stratified approach for gastric cancer screening.
While individuals with Lynch syndrome have a known risk for developing some gastrointestinal cancers, including colorectal cancer, Matthew B. Yurgelun, MD, of Dana Farber Cancer Institute, and colleagues wrote that less is known about the factors that predispose carriers to other malignancies.
“Addressing this knowledge gap is of particular importance with respect to gastric cancer, since it is a particularly lethal cancer with a less than 30% 5-year overall survival in the United States across all disease stages, and only minimal improvements in early detection rates have been appreciated over recent years,” they wrote in Clinical Gastroenterology and Hepatology.
Researchers collected data from 52,758 individuals who were tested for genetic variants associated with Lynch syndrome between 2006 and 2013. They used clinical and demographic data, as well as information on personal and family history of cancer to identify clinical factors associated with gastric cancer.
Of the overall cohort, 3,828 individuals carried pathogenic mutations, including 1,346 with mutations in MLH1, 1,639 with mutations in MSH2, 670 with mutations with MSH6, 145 with mutations in PMS2 and 28 with mutations in EPCAM. Among these individuals, 41 had a previous gastric cancer, and 350 had one or more first- or second-degree relative with gastric cancer.
In their analysis, Yurgelun and colleagues determined that male sex (OR = 2.82; 95% CI, 1.48–5.38), older age (OR = 2.07 per 10 years; 95% CI, 1.64–2.61) and having a first-degree family member with gastric cancer (OR = 2.52; 95% CI, 1.42–4.45) were independently associated with gastric cancer among carriers of pathogenic mutations. Mutations in MLH1 (OR = 6.53; 95% CI, 1.5–28.42) or MSH2 (OR = 5.23 compared with mutations in MSH6, PMS2, or EPCAM; 95% CI, 1.21–22.71).
Having a second-degree relative was not independently associated with cancer.
“Interestingly, male sex, age, and family history of [gastric cancer] are all known risk factors for sporadic, non-[Lynch syndrome] [gastric cancer] as well, raising the hypothesis that other traditional [gastric cancer] risk factors may likewise compound the inherited [gastric cancer] risk seen in [Lynch syndrome] carriers,” they wrote. “Together, such data can facilitate the development and assessment of personalized risk-stratified early detection strategies in [Lynch syndrome] carriers at highest risk for [gastric cancer], while also suggesting that carriers lacking these factors might be able to safely forego low-yield and potentially unnecessary [esophagogastroduodenoscopy] surveillance.” – by Alex Young
Disclosures: Yurgelun reports no relevant financial disclosures. Please see the full study for all other authors’ relevant financial disclosures.
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