Pauline Anderson

June 09, 2011

June 9, 2011 (Toronto, Ontario) — Having the G2019S mutation of the LRRK2 gene, which is associated with the most common autosomal dominant form of Parkinson's disease (PD), increases risks for nonskin cancers, particularly breast cancer, among Jewish PD patients, a new study suggests.

"The importance of this finding is that there is probably an oncogenic activity of this gene, or it's activating another gene that is oncogenic, so it also has importance for cancer research," said lead study author Rivka Inzelberg, MD, professor of neurology, Chaim Sheba Medical Center, Tel Hashomer, Israel.

Although it's too early to say definitively, this mutation could signal a new risk for breast cancer in addition to the 2 gene mutations already known to be strongly linked to breast cancer, BRCA1 and BRCA2.

Dr. Inzelberg presented her study at the Movement Disorder Society (MDS) 15th International Congress of Parkinson's Disease and Movement Disorders.

Carriers and Noncarriers

The study included 490 Jewish PD patients, 88% of whom were Ashkenazi Jewish. Researchers examined blood leukocytes for the G2019S mutation of the LRRK2 gene from extracted DNA. They gathered information on malignant tumors through questionnaires from patients during intake at outpatient clinics.

After dividing the patients into those who were carriers of the gene (n = 79) and those who weren't (n = 411), the researchers found that the 2 groups were about the same age (mean age, 70 vs 68 years), had a similar mean duration of PD (10 vs 9 years), and had a similar percentage of patients taking levodopa treatment (77% and 83%).

However, the proportion of women was much larger among carriers (39 women and 40 men) compared with noncarriers (152 women and 259 men). More carriers (44%) had a positive family history of PD compared with noncarriers (20%).

Of the total sample, 77 patients (16%) had a cancer, and of these, 2% had 2 primary cancers. Many of these cancers (23% in carriers and 12% in noncarriers) were nonskin cancers (P = .01). The most common cancer was breast cancer, which represented 15% of cancers in carriers and 5% in noncarriers.

There was no difference in type of cancer between Ashkenazi and non-Ashkenazi Jewish subjects, said Dr. Inzelberg. She pointed out, however, that there were only 160 non-Ashkenazi Jews, and of those, only 9 had the LRRK2 gene mutation, "so the numbers are very small."

The specific LRRK2 genetic mutation is common among North African Arabs and Ashkenazi Jews, said Dr. Inzelberg.

Breast Cancer Gene

Only 1 patient in the study carried a BRCA gene. "This is very important; it's possible that this gene has something to do with another breast cancer gene that has not yet been found," said Dr. Inzelberg. "Is it only in Parkinson's disease? Is it also in all Ashkenazi women without Parkinson's? We don't know yet."

It's too early to advise all Ashkenazi Jewish women to be tested for the LRRK2 mutation, but this might be something to consider in a breast cancer population that has tested negative for the known breast cancer genes, said Dr. Inzelberg.

The next step for Dr. Inzelberg and her colleagues is to expand the study to a larger population. "We are genotyping all our patients now for LRRK2 and taking information about breast and other cancers."

If a larger study comes to the same conclusion, "we have to implement a prevention program" that would include more widespread mammography, she said.

Results Surprising

Approached for a comment, David A. Grimes, MD, director, Parkinson's Disease and Movement Disorders Clinic, Ottawa Hospital Civic Campus, Ontario, Canada, found the study results "very surprising" because previous studies had found a link between PD and skin cancers but not with other types of cancer.

Dr. Grimes said that it's odd that no connection between LRRK2 and nonskin cancers has been found in the past, considering this mutation is one of the most common genetic factors involved in PD.

"You would think that there would have been some hint along the way in the last 50 years, that we would have seen it or that someone else would have thought of it, especially in families, as there are large families with multiple people affected," he said.

It's possible that specialists who focus on neurologic problems may not zero in on cancer. "But there have been so many epidemiological studies that you'd think something would have popped up," said Dr. Grimes.

At least 6 genes have a known direct link to PD, whereas other genes carry "a susceptibility factor" related to PD, said Dr. Grimes. In the case of LRRK2, having the mutation gives people a susceptibility to developing PD. The LRRK2 mutation seems to be tied in some way to the immune system, said Dr. Grimes.

The study authors and Dr. Grimes have disclosed no relevant financial relationships.

Movement Disorder Society (MDS) 15th International Congress of Parkinson's Disease and Movement Disorders: Abstract 925. Presented June 8, 2011.


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