December 18, 1998

Infection, testicular cancer link investigated

Infection, testicular cancer link investigated

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Loren Lipworth

A Vanderbilt Cancer Center epidemiologist is one of two researchers in the country to receive the first grants awarded by the Lance Armstrong Foundation to fund testicular cancer research.

Loren Lipworth, Sc.D., assistant professor of Preventive Medicine, is studying a possible link between infection and the development of testicular cancer, one of the most rapidly increasing forms of cancer.

A relationship between infection and testicular cancer could have significant implications for the prevention of the disease, which accounts for only about 1 percent of all cancers in men but is among the most common cancers among men ages 15-34.

"The age-standardized incidence of testicular cancer is increasing by about 3-6 percent each year, which suggests a relationship with external factors," said Lipworth, who joined the faculty in June.

"Some of the classic virus-associated cancers, like Hodgkin's disease, exhibit the same sort of age-incidence pattern as testicular cancer, peaking in the 20s and 30s and then dropping off dramatically. For virtually every other form of cancer not associated with viruses, the incidence continues to increase with age."

Olympic cyclist Lance Armstrong established the foundation in early 1997, just months after he was diagnosed with advanced testicular cancer. The first Lance Armstrong Foundation grants were awarded Oct. 23 to Lipworth and an M.D. Anderson researcher studying the neurocognitive effects of chemotherapy. The $50,000-per-year awards are renewable for up to three years.

Lipworth's research makes use of the JANUS serum bank in Norway. Established in 1973 for the purpose of cancer research, JANUS includes about a half million serum samples given over a 20-year period by about 293,000 donors. Individual blood donors are then annually linked to the Norwegian national cancer registry to identify who has gone on to develop cancer.

So far, 88 cases of testicular cancer have been identified, Lipworth said.

"We'll look at these 88 cases and compare them to 262 matched control samples," she said. "We will assay the serum for the presence of antibodies against several infectious agents, including herpes simplex virus 2, human papilloma virus (HPV), chlamydia trachomatis and human herpes virus 8 (HHV8)."

Preliminary analyses have already been done for the Epstein-Barr virus (EBV) and cytomegalovirus (CMV), she said.

"We have found some interesting trends, though not necessarily statistically significant because of the small sample size," Lipworth said. "There was a positive two- to three-fold increase in testicular cancer risk among men with higher antibody titers to EBV."

With CMV, no overall correlation was found, she said. However, when the cases were divided by histologic type ‹ seminomas and non-seminomas ‹ a positive relationship was observed between CMV seropositivity and the development of seminomas.

"Because both these viruses are sexually transmitted, we decided that it made sense to look at other sexually transmitted viruses," Lipworth said. Thus far, a preliminary analysis of 20 of the testicular cancer cases revealed a positive, though non-significant, trend for chlamydia antibody titers. Next, the researchers will examine all 88 cases for evidence of infection with each of the viruses.

Lipworth, who also holds appointments with the Karolinska Institute in Stockholm and the International Epidemiology Institute in Rockville, Md., is a graduate of the Harvard School of Public Health. Much of her research is done in collaboration with researchers in Sweden using that country's national registries for inpatient care, outpatient care, cancer, mortality and so on.

In addition to testicular cancer, Lipworth has a particular research interest in endogenous hormonal risk factors for cancer.

For example, recent work used such characteristics as birthweight, birth length and placental weight as surrogate markers for estrogen or other hormone or growth factor exposure during pregnancy. These studies examined the relationship of these characteristics to the development of breast, prostate and testicular cancer.

She also has conducted a study measuring the levels of estrogen and other hormones and growth factors during pregnancy in white women in Boston, Mass., and comparing that with levels in women in China.

"There is some kind of positive association between higher birthweight and increased risk of breast and prostate cancer," Lipworth said. "Our initial hypothesis was that the key was estrogen ‹ more estrogen, bigger baby, higher risk. However, our preliminary analysis of the hormone studies shows that the Chinese women actually have substantially higher levels of estrogen than the American women, but they have a substantially lower breast cancer rate. Now we suspect that it's not estrogen, after all, but perhaps another growth factor."

Lipworth expects to present findings from the comparison of the American and Chinese women at a National Cancer Institute conference on intrauterine exposures and breast cancer early next year.