JAMA Oncol: Hereditary cancer susceptibility gene variants in patients with appendix cancer

Germline variants in APC, BMPR1A, CDH1, CHEK2, EPCAM, MLH1, MSH2, MSH6, MUTYH, PMS2, PTEN, SMAD4, STK11, and TP53 genes are associated
with susceptibility to gastrointestinal cancer.
As a rare cancer, susceptibility to appendix cancer has not been adequately evaluated
.

This study evaluated the incidence of genetic cancer-susceptibility gene sequence variation in patients with appendix cancer, as well as the usefulness
of germline gene testing in this population.

Patients with appendix cancer who were tested for germline variants of 14 cancer susceptibility genes in a clinical testing laboratory between 1 March 2012 and 31 December 2016 were included
.
Obtain the patient's clinical, personal, and family history
from the examination request form completed by the clinician.
Multi-genome testing uses targeted custom capture, sequencing, and chromosome rearrangement analysis
.
The primary endpoints were germline variability, incidence, and spectrum
in patients with appendiceal cancer.

Detected genetic variants

Of the 131 patients with appendiceal cancer (90 women [68.
7%]), a total of 16 harmful variants
were detected in 15 patients (11.
5%).
Similarly, of the 74 patients with appendicitis as the first and only primary tumor, 8 (10.
8%) carried at least one harmful variant
of the cancer susceptibility gene.
Overall, 6 (4.
6%) patients carried harmful variants of the MUTYH gene (5 single-allele MUTYH gene variants and 1 biallelic MUTYH gene variant).

All 4 patients with Lynch syndrome carried MLH1 gene variants, and 3 of them were diagnosed with appendix cancer at the age of 50 and older
.
Five (3.
8%) patients carried harmful variants in other cancer susceptibility genes (1 case APC [c.
3920T>A, p.
I1307K], 2 cases CHEK2 [c.
470T>C, p.
I157T], 1 case SMAD4 [c.
263 287dup, p.
L98IFS*14] and 1 case TP53 [c.
524G>A, p.
R175H]).

Overall, one in 10 patients with appendix cancer tested for hereditary cancer susceptibility carries a genetic variant
associated with cancer susceptibility.
Given the high frequency and broad spectrum of germline gene variation, these data suggest that genetic evaluation
may be required in all patients diagnosed with this rare malignancy.

Original source:

Holowatyj AN, Washington MK, Tavtigian SV, Eng C, Horton C.
Inherited Cancer Susceptibility Gene Sequence Variations Among Patients With Appendix Cancer.
JAMA Oncol.
Published online November 11, 2022.
doi:10.
1001/jamaoncol.
2022.
5425