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“My team conducted a few studies, particularly one that wanted to look at the burden of appendix cancers in young adults,” she said. “And what we strikingly found there was that, in contrast to the fact that about 1 in every 5 colorectal cancer patients is diagnosed before the age of 50, we found that 1 in every 3 [30.8%] appendix cancer patients are diagnosed before age 50.4. Noting this really disproportionate burden in younger patients really spurred a lot of the subsequent work that my lab has done and continues to do."

Dr. Holowatyj recently led a study that discovered the first genetic link to appendix cancer. "In this cohort study of 131 patients with appendix cancer who underwent clinical multigene panel testing, 11.5% harbored a pathogenic sequence variation. Among 74 patients with appendix cancer as the first and only primary tumor, a similar proportion (10.8%) carried a pathogenic sequence variation." The findings suggest that appendiceal cancer may be a previously underrecognized indication for hereditary cancer genetic testing (or a hereditary cancer syndrome) and that genetic evaluation should be considered for all patients with appendix cancer.

"While there is still much to learn from our discovery, we have found the tip of an iceberg -- potentially a really big iceberg," Holowatyj said in a center news release. Historically, experts have not thought this cancer, which affects about one or two people in 1 million annually, was hereditary. The fact that it's rare has made it even harder to understand and study.

Researchers found that 11.5% of the patients had at least one inherited genetic variant in a cancer susceptibility gene. In the patients whose appendix cancer was the first and only primary tumor, researchers noted a similar prevalence, about 10.8%. This further links the disease to a familial component.

Appendiceal cancer affects about one or two people per million annually. Historically it has been thought that appendiceal cancer is not hereditary, but its rarity has presented challenges for understanding the characteristics of the disease and developing therapies. A research team led by Andreana Holowatyj, PhD, MSCI, assistant professor of Medicine and Cancer Biology at Vanderbilt University Medical Center, analyzed multigene panel testing data from a nationwide clinical testing laboratory in the U.S. for a total of 131 patients with appendiceal cancer. 

“Given the high frequency and broad spectrum of germline gene sequence variations, these data suggest that genetic evaluation might be warranted for all patients diagnosed with this rare malignant tumor,” the researchers wrote. “A systemic sequencing effort for all patients with AC [appendix cancer] may also identify cancer vulnerabilities to exploit for therapeutic development in a cancer type for which clinical trials are limited.”

One of every 10 patients with appendiceal cancer carries a germline genetic variant associated with cancer predisposition, according to a study in JAMA Oncology that is the first to show inherited risk factors for this rare cancer.

Although appendiceal cancer is rare, it is becoming more common for reasons that are not known. Last year, Holowatyj and colleagues conducted the first study of appendiceal cancer patterns and survival among patients younger than 50 (early-onset disease) in the U.S. They found poorer disease outcomes among non-Hispanic Blacks compared to non-Hispanic whites, and among men compared with women.

In the patients whose appendix cancer was the first and only primary tumor, researchers noted a similar prevalence, about 10.8%. This further links the disease to a familial component.

Andreana N. Holowatyj, Ph.D., from the Vanderbilt University Medical Center in Nashville, Tennessee, and colleagues examined the prevalence and spectrum of inherited cancer susceptibility gene sequence variations in a cohort of patients with AC who underwent germline genetic testing of 14 cancer susceptibility genes. The cohort included 131 patients with AC.

About 10 percent of patients with appendix cancer (AC) who undergo testing for hereditary cancer disposition harbor a gene sequence variation associated with cancer susceptibility, according to a study published online Nov. 11 in JAMA Oncology.

"These findings support the consideration of genetic testing for all patients with appendix cancer irrespective of age or family history," the authors write. "The consideration of a more systemic sequencing effort for all patients with appendiceal cancer may provide important evidence toward tailoring genes selected for germline genetic testing for appendiceal cancer across specific patient groups."

Six patients (4.6 percent) had a deleterious sequence variation in MUTYH (five monoallelic and one biallelic). Four patients (3.1 percent) had Lynch syndrome and had a sequence variation in the MLH1 gene; three were aged 50 years or older at AC diagnosis. Deleterious sequence variations in other cancer predisposition genes (APC, CHEK2, SMAD4, and TP53) were seen for five patients (3.8 percent).

The researchers identified 16 deleterious sequence variations in 15 patients (11.5 percent). When limited to the 74 patients with AC as the first and only primary tumor, eight patients (10.8 percent) had at least one deleterious sequence variation in a cancer susceptibility gene. 

Andreana N. Holowatyj, Ph.D., from the Vanderbilt University Medical Center in Nashville, Tennessee, and colleagues examined the prevalence and spectrum of inherited cancer susceptibility gene sequence variations in a cohort of patients with AC who underwent germline genetic testing of 14 cancer susceptibility genes. The cohort included 131 patients with AC.

About 10 percent of patients with appendix cancer (AC) who undergo testing for hereditary cancer disposition harbor a gene sequence variation associated with cancer susceptibility, according to a study published online Nov. 11 in JAMA Oncology.

"These findings support the consideration of genetic testing for all patients with appendix cancer irrespective of age or family history," the authors write. "The consideration of a more systemic sequencing effort for all patients with appendiceal cancer may provide important evidence toward tailoring genes selected for germline genetic testing for appendiceal cancer across specific patient groups."

Six patients (4.6 percent) had a deleterious sequence variation in MUTYH (five monoallelic and one biallelic). Four patients (3.1 percent) had Lynch syndrome and had a sequence variation in the MLH1 gene; three were aged 50 years or older at AC diagnosis. Deleterious sequence variations in other cancer predisposition genes (APC, CHEK2, SMAD4, and TP53) were seen for five patients (3.8 percent).

The researchers identified 16 deleterious sequence variations in 15 patients (11.5 percent). When limited to the 74 patients with AC as the first and only primary tumor, eight patients (10.8 percent) had at least one deleterious sequence variation in a cancer susceptibility gene.

Andreana N. Holowatyj, Ph.D., from the Vanderbilt University Medical Center in Nashville, Tennessee, and colleagues examined the prevalence and spectrum of inherited cancer susceptibility gene sequence variations in a cohort of patients with AC who underwent germline genetic testing of 14 cancer susceptibility genes. The cohort included 131 patients with AC.

About 10 percent of patients with appendix cancer (AC) who undergo testing for hereditary cancer disposition harbor a gene sequence variation associated with cancer susceptibility, according to a study published online Nov. 11 in JAMA Oncology.

Six patients (4.6 percent) had a deleterious sequence variation in MUTYH (five monoallelic and one biallelic). Four patients (3.1 percent) had Lynch syndrome and had a sequence variation in the MLH1 gene; three were aged 50 years or older at AC diagnosis. Deleterious sequence variations in other cancer predisposition genes (APC, CHEK2, SMAD4, and TP53) were seen for five patients (3.8 percent).

The researchers identified 16 deleterious sequence variations in 15 patients (11.5 percent). When limited to the 74 patients with AC as the first and only primary tumor, eight patients (10.8 percent) had at least one deleterious sequence variation in a cancer susceptibility gene. 

Andreana N. Holowatyj, Ph.D., from the Vanderbilt University Medical Center in Nashville, Tennessee, and colleagues examined the prevalence and spectrum of inherited cancer susceptibility gene sequence variations in a cohort of patients with AC who underwent germline genetic testing of 14 cancer susceptibility genes. The cohort included 131 patients with AC.

About 10 percent of patients with appendix cancer (AC) who undergo testing for hereditary cancer disposition harbor a gene sequence variation associated with cancer susceptibility, according to a study published online Nov. 11 in JAMA Oncology.

"These findings support the consideration of genetic testing for all patients with appendix cancer irrespective of age or family history," the authors write. "The consideration of a more systemic sequencing effort for all patients with appendiceal cancer may provide important evidence toward tailoring genes selected for germline genetic testing for appendiceal cancer across specific patient groups."

Six patients (4.6 percent) had a deleterious sequence variation in MUTYH (five monoallelic and one biallelic). Four patients (3.1 percent) had Lynch syndrome and had a sequence variation in the MLH1 gene; three were aged 50 years or older at AC diagnosis. Deleterious sequence variations in other cancer predisposition genes (APC, CHEK2, SMAD4, and TP53) were seen for five patients (3.8 percent).

The researchers identified 16 deleterious sequence variations in 15 patients (11.5 percent). When limited to the 74 patients with AC as the first and only primary tumor, eight patients (10.8 percent) had at least one deleterious sequence variation in a cancer susceptibility gene.

Andreana N. Holowatyj, Ph.D., from the Vanderbilt University Medical Center in Nashville, Tennessee, and colleagues examined the prevalence and spectrum of inherited cancer susceptibility gene sequence variations in a cohort of patients with AC who underwent germline genetic testing of 14 cancer susceptibility genes. The cohort included 131 patients with AC.

About 10 percent of patients with appendix cancer (AC) who undergo testing for hereditary cancer disposition harbor a gene sequence variation associated with cancer susceptibility, according to a study published online Nov. 11 in JAMA Oncology.

For this research, Holowatyj and her colleagues analyzed multi-gene panel testing data from a nationwide clinical testing laboratory in the United States. The data included 131 patients with appendiceal cancer.

Historically, experts have not thought this cancer, which affects about one or two people in 1 million annually, was hereditary. The fact that it's rare has made it even harder to understand and study.

"While there is still much to learn from our discovery, we have found the tip of an iceberg -- potentially a really big iceberg," Holowatyj said in a center news release.

"Based on these data, we are able to recommend genetic counseling and multi-gene panel testing of cancer susceptibility genes for all appendix cancer patients, regardless of age or family history of cancer," said researcher Andreana Holowatyj. She's an assistant professor of medicine and cancer biology at Vanderbilt University Medical Center in Nashville, Tenn.

Researchers built on earlier research with this study, finding that 1 in 10 people with cancer of the appendix carries a genetic variant associated with cancer predisposition. 

While appendix cancer is rare, for a small percentage of patients the disease may be linked to a particular genetic variant, a new study suggests.