Using Family History to Guide Surveillance of “Other” Cancers in Lynch Syndrome: Does That Work?
Douglas K. Rex, MD, MASGE, reviewing Biller LH, et al. Gastroenterology 2021 Mar 25.
The “other” cancers in Lynch syndrome include small-bowel, pancreatobiliary, urinary tract, and brain cancers, as well as sebaceous neoplasms. Routine screening for many of these cancer types is often not performed unless there is a family history of the particular cancer type.
In an analysis of 2 cohorts that included a total of more than 4400 carriers of Lynch syndrome, multivariable analysis of age, sex, mutation, and family history was used to determine whether a family history of other cancers indeed predicts the risk of those same cancers in patients with Lynch syndrome.
In the larger cohort of 3800 patients, male sex was associated with colorectal cancer (CRC; odds ratio [OR], 4.8), urinary tract cancer (OR, 1.9), small-bowel cancer (OR, 3.8), sebaceous neoplasms (OR, 1.8), and gastric cancer (OR, 3.0). MLH1 (relative to MSH6 or PMS2) was associated with CRC (OR, 3.7) and gastric cancer (OR, 6.6). MSH2 was associated with CRC (OR, 1.8), gastric cancer (OR, 5.2), urinary tract cancer (OR, 4.0), small-bowel cancer (OR, 2.5), and sebaceous neoplasms (OR, 4.3). Familial history of cancer (OR per affected first- or second-degree relative) was associated with the same type of cancer in patients with Lynch syndrome for endometrial (OR, 1.4), ovarian (OR, 1.3), urinary tract (OR, 2.7), small-bowel (OR, 3.2), gastric (OR, 1.9), and pancreatobiliary cancers (OR, 2.1) and sebaceous neoplasms (OR, 7.4).
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COMMENTThese data confirm that a family history of other cancers in first- or second-degree relatives is an important predictor of risk for the same cancers in patients with Lynch syndrome. The odds ratios are particularly high for sebaceous neoplasms, and small-bowel, urinary tract, and pancreatobiliary cancers. Used in combination with age, sex, and affected genes, family history can be used to design personalized surveillance approaches.
Note to readers: At the time we reviewed this paper, its publisher noted that it was not in final form and that subsequent changes might be made.
CITATION(S)
Biller LH, Horiguchi M, Uno H, Ukaegbu C, Syngal S, Yurgelun MB. Familial burden and other clinical factors associated with various types of cancer in individuals with Lynch syndrome. Gastroenterology 2021 Mar 25. (Epub ahead of print) (https://doi.org/10.1053/j.gastro.2021.03.039)