Mutations in a gene that impacts immune function increase susceptibility to prostate cancer

August 29, 2013

A team of researchers led by Janet Stanford, Ph.D., of Fred Hutchinson Cancer Research Center has discovered that mutations in the gene BTNL2, which encodes a protein involved in regulating T-cell proliferation and cytokine production – both of which impact immune function – increase the risk of developing prostate cancer.

The findings, by Stanford and colleagues from the University of Washington Genome Sciences Department and the National Human Genome Research Institute, are online ahead of the print issue of Cancer Epidemiology, Biomarkers & Prevention.

A complex disease with a strong genetic component

Prostate cancer is a complex disease and its causes include a strong genetic component. It is estimated that about 42 percent of prostate cancer cases are due to heredity, or genetic variations present at birth. Five to 10 percent of those prostate cancer cases are thought to result from rare inherited mutations.

The researchers studied multiple prostate cancer patients from families with a pattern of hereditary prostate cancer, or HPC. Germline DNA provided by patients with more aggressive or early onset disease was sequenced in an attempt to identify rare genetic mutations that predispose to prostate cancer. All the participants were men of European ancestry.

Several genes with candidate mutations were highlighted, but two coding variants in the butyrophilin-like 2, or BTNL2, gene were most strongly related to the development of prostate cancer. These missense mutations that change the genetic code were subsequently confirmed to be clearly associated with prostate cancer in an independent set of HPC families and in a case-control study population.

The team found that the two BTNL2 mutations associated with elevated prostate cancer risk are rare. In the 270 HPC families used for confirmation, about 1.5 percent of affected men carried one of the mutations but unaffected men carried none. In the population-based case-control study, 2 percent of prostate cancer cases and less than 1 percent of men without prostate cancer carried one of the variants.

Mutations increased risk of both hereditary and sporadic prostate cancer

In the case-control study, men who carried one of these variants had a significant 2.5- to 2.7-fold higher risk for developing prostate cancer compared to men who did not carry either mutation.

"This research demonstrates for the first time that rare mutations in the BTNL2 gene enhance susceptibility to both hereditary and sporadic prostate cancer," said Stanford, co-director of the Program in Prostate Cancer Research a member of the Public Health Sciences Division at Fred Hutch. Common variants in this gene have been previously linked to several autoimmune and inflammatory diseases such as sarcoidosis and ulcerative colitis.

The researchers used a next-generation sequencing technology called whole-exome sequencing, which consists of sequencing all the coding regions, called exons, across the genome. The researchers used this technique to identify genetic variations within 91 men from 19 HPC families. Then, 130 candidate mutations that were observed more frequently in the men with prostate cancer were evaluated in an independent set of 270 HPC families for further confirmation.

Other candidate found in this whole-exome sequencing study will be evaluated in a future investigation involving a larger group of HPC families and case-control populations to further assess their link to .

Explore further: Study finds genetic mutation in castration-resistant prostate cancer

Related Stories

Study finds genetic mutation in castration-resistant prostate cancer

August 29, 2013
The mutation occurs in the androgen-synthesizing enzyme 3βHSD1 in castration-resistant prostate cancer (CRPC), according to research published online today in Cell. This mutation enables the tumor to make its own supply ...

Prostate cancer risk rises in men with inherited genetic condition

April 1, 2013
Men with an inherited genetic condition called Lynch syndrome face a higher lifetime risk of developing prostate cancer and appear to develop the disease at an earlier age, according to a new study led by researchers at the ...

Researchers identify genetic variants predicting aggressive prostate cancers

June 19, 2013
Researchers at Moffitt Cancer Center and colleagues at Louisiana State University have developed a method for identifying aggressive prostate cancers that require immediate therapy. It relies on understanding the genetic ...

Early-onset baldness in African-American men may be linked to prostate cancer

March 26, 2013
Baldness was associated with an increased risk of prostate cancer among African-American men, and risk for advanced prostate cancer increased with younger age and type of baldness, according to data published in Cancer Epidemiology, ...

First genetic factor in prostate cancer prognosis identified

April 9, 2013
Patients with prostate cancer and hereditary mutations in the BRCA2 gene have a worse prognosis and lower survival rates than do the rest of the patients with the disease. This is the main conclusion to come out of a study ...

Recommended for you

New therapeutic approach for difficult-to-treat subtype of ovarian cancer identified

July 24, 2017
A potential new therapeutic strategy for a difficult-to-treat form of ovarian cancer has been discovered by Wistar scientists. The findings were published online in Nature Cell Biology.

Immune cells the missing ingredient in new bladder cancer treatment

July 24, 2017
New research offers a possible explanation for why a new type of cancer treatment hasn't been working as expected against bladder cancer.

Shooting the achilles heel of nervous system cancers

July 20, 2017
Virtually all cancer treatments used today also damage normal cells, causing the toxic side effects associated with cancer treatment. A cooperative research team led by researchers at Dartmouth's Norris Cotton Cancer Center ...

Molecular changes with age in normal breast tissue are linked to cancer-related changes

July 20, 2017
Several known factors are associated with a higher risk of breast cancer including increasing age, being overweight after menopause, alcohol intake, and family history. However, the underlying biologic mechanisms through ...

Immune-cell numbers predict response to combination immunotherapy in melanoma

July 20, 2017
Whether a melanoma patient will better respond to a single immunotherapy drug or two in combination depends on the abundance of certain white blood cells within their tumors, according to a new study conducted by UC San Francisco ...

Discovery could lead to better results for patients undergoing radiation

July 19, 2017
More than half of cancer patients undergo radiotherapy, in which high doses of radiation are aimed at diseased tissue to kill cancer cells. But due to a phenomenon known as radiation-induced bystander effect (RIBE), in which ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.