NEW YORK (Reuters) - Medical researchers call it the "Angelina Effect," the surge in demand for genetic testing attributable to movie star Angelina Jolie's public crusade for more aggressive detection of hereditary breast and ovarian cancer.

But there's a catch: Major insurance companies including Aetna, Anthem and Cigna are declining to pay for the latest generation of tests, known as multi-gene panel tests, Reuters has learned.

The insurers say that the tests are unproven and may lead patients to seek out medical care they don't need. That's a dangerous miscalculation, a range of doctors, genetic counselors, academics and diagnostics companies said.

While they acknowledge that multi-gene tests produce data that may not be useful from a diagnostic standpoint, they say that by refusing or delaying coverage, insurance companies are endangering patients who could be undergoing screenings or changing their diets if they knew about the possible risks.

The tests have come a long way since Jolie, 39, went public in 2013, revealing that she underwent a double mastectomy after a genetic test found she carried mutations in the BRCA1 and BRCA2 genes, indicating a high risk of breast and ovarian cancer.

She disclosed last month that she had her ovaries and fallopian tubes removed.

The new panel tests, which can cost between $2,000 to $4,900, analyze 20 or more genes at once. That allows healthcare professionals to establish possible DNA links to other cancer-related conditions such as Lynch syndrome and Li-Fraumeni Syndrome earlier. Humans have about 23,000 genes. Susan Kutner, a surgeon at a Kaiser Permanente hospital in San Jose, California, who serves on a U.S. Centers for Disease Control and Prevention advisory committee on young women and breast cancer, said more women with a family history of cancer should be able get these tests.

"If we have members who are not being tested in a timely manner, we know that their risk of cancer in the long run costs us and them a lot more," Kutner said.

Kaiser, which insures its own members, covers panel tests for patients with family histories of cancer. That's not so at three of the four largest managed care companies. Aetna Inc, Anthem Inc and Cigna Corp state in their policies that in most cases they don't cover multi-gene panel tests. The fourth, UnitedHealth Group, covers the tests if patients meet certain criteria.

All insurers cover screenings for BRCA1 and BRCA2 and for certain other genes for women who have family histories of cancer.

Indeed, such coverage is mandated by the Affordable Care Act, known as Obamacare. But many insurers said they simply don't know enough about the specific risk of other mutations to justify coverage of the new family of tests.

They also say that the tests may find mutations with a well-established link to a disease, but which are difficult to interpret.

These results could lead to patients taking misguided actions about medical care, such as preventive chemotherapy and surgery. Aetna's medical director of quality management, Robert McDonough, said Aetna pays for testing of individual genes but that "the routine application of a panel would be considered unproven." Cigna's David Finley, national medical officer for enterprise affordability, said multi-gene tests are more likely to find unknown mutations for which there are no care guidelines.

"This is where there is controversy and disagreement," Finley said. "My problem is what do you do with that information?"

Instead, he said, there need to be more clinical trials and research to establish exact risks and medical guidelines for each type of gene mutation. Healthcare professionals said that while they recognize the downside of patients getting unclear information about their genetic makeup, genetic counseling and support from doctors can mitigate risks. CATCH-22 Mary Daly, a physician who chairs the National Comprehensive Cancer Network guidelines panel for breast and ovarian cancer, oversees the process for setting guidelines that most doctors in this field follow.

She points to what is, in effect, a "Catch 22:" Without insurance coverage of these tests, there isn't enough data to analyze how effective they are.

"If we don't start looking at these genes, we'll never obtain the data we need," she said.

Leading academics in genetic research also dispute the claim that multi-gene tests produce too much confusing information, saying they often lead to beneficial steps such as cancer screenings.

"The utility of panel testing is that we know there are a lot more genes beyond BRCA1 and BRCA2 that are associated with cancer predisposition," said Colin Pritchard, a University of Washington geneticist. Pritchard said the understanding of the link between genetic mutations and cancer is evolving quickly.

A recent study in the New England Journal of Medicine established rates of breast cancer associated with a mutation in one of the genes included in many of these panel tests, known as the PALB2 gene. Hereditary cancers are expected to account for about 5 percent of the 230,000 cases of invasive breast cancer that will be diagnosed this year in the United States. In the year Jolie went public about her testing, an AARP Public Policy Institute study found that BRCA testing had risen 40 percent.

Jolie’s spokesperson did not return a call requesting comment on the multi-gene testing trend. Myriad Genetics Inc, which accounts for 90 percent of the hereditary cancer-testing market, said 15 of the 25 genes that National Comprehensive Cancer Network guidelines indicate should be included in multi-gene testing are in its "MyRisk" panel test.

The business represents a $5 billion global market opportunity for Myriad, the company said in January. Other lab companies including Ambry Genetics, Quest Diagnostics Inc and Invitae Corp each offer a variety of panels that start at about seven genes and go up to 40 genes.

"In general, the trend is moving toward more genes,” said Carin Espenschied, a senior products manager at Ambry and a genetic counselor. "Research and insurance companies kind of just have to catch up."

(Reporting by Caroline Humer, editing by Michele Gershberg, Eric Effron and John Pickering)