July 5, 2005

Other highlights in the July 6 Journal of the National Cancer Institute

A new study has found that long-duration regular use of aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs, such as ibuprofen) may be associated with a reduced risk of prostate cancer.

Use of aspirin and other NSAIDs has been consistently associated with a reduced risk of colorectal cancer in epidemiological studies, and aspirin reduced risk of colorectal polyp recurrence in two randomized trials. There has also been some evidence from laboratory and epidemiological studies that NSAIDs might influence prostate carcinogenesis, although the association is unclear.

To determine whether use of NSAIDs is associated with a reduced risk of prostate cancer, Eric J. Jacobs, Ph.D., of the American Cancer Society in Atlanta, and colleagues studied more than 70,000 men participating in the American Cancer Society's Cancer Prevention Study II Nutrition Cohort. During the follow-up from 1992 to 1993 through August 2001, 4,853 cases of prostate cancer were diagnosed among these men.

Current use of aspirin or any NSAID was not associated with prostate cancer risk. However, long-duration regular use (30 or more pills per month for 5 or more years) of aspirin or any NSAID was associated with an estimated 18% reduction in the relative risk of prostate cancer. In the population studied, the age-adjusted rate of prostate cancer was 1,013 cases per 100,000 person-years among men who never reported NSAID use compared with 847 cases per 100,000 person-years among long-duration NSAID users.

"In this large prospective study, long-duration regular NSAID use was associated with a modest reduction in prostate cancer risk," the authors write. "In our view, it would be premature to consider reduced risk of prostate cancer a benefit of using aspirin or other NSAIDs because to date there are relatively few large observational studies and no randomized trials addressing this question."

Contact: David Sampson, Media Relations, American Cancer Society, 213-368-8523, [email protected]

Gene Variants Associated With Melanoma Risk and Progression in Mediterranean Population

A study conducted in a Mediterranean population has found that variants of the melanocortin-1 receptor (MC1R) gene are associated with melanoma risk and progression, particularly in the absence of other major risk factors, such as freckling or many nevi (moles).

Specific genetic variants of the MC1R gene have been associated with fair pigmentation and melanoma risk, and a polymorphism of the Agouti Signaling Protein (ASIP) has been associated with dark pigmentation in Northern Europeans. However, the melanoma risks associated with these genetic variants have not been studied in a Mediterranean population--a population that is typically at low risk of developing melanoma.

To examine MC1R and ASIP genotypes and melanoma risk in a Mediterranean population, Maria Teresa Landi, M.D., Ph.D., of the National Cancer Institute, and colleagues studied 267 melanoma patients and 382 control subjects from a case"“control study and a family study in northeastern Italy. This population was mostly negative for mutations in other melanoma candidate genes.

The researchers found a two- to fourfold increased risk of sporadic and familial melanoma in individuals who carried MC1R variant genotypes when compared with carriers of the wild-type MC1R genotype. Subjects who carried particular variants of the MC1R gene were more likely to have lighter pigmentation and freckling, but the association of MC1R variants with melanoma risk was stronger in subjects with darker pigmentation, no freckling, and fewer nevi. They also report that individuals who carry MC1R variant genotypes were more likely to have thick melanomas than those with the wild-type MC1R genotype. In contrast, no association with the ASIP polymorphism was observed.

Contact: National Cancer Institute Press Office, 301-496-6641, [email protected]

Gene Mutations in Colorectal Tumors Not Associated With Response to Bevacizumab

Mutations in the genes k-ras, b-raf, or p53 in the tumors of colorectal cancer patients are not associated with a differential response to the monoclonal antibody bevacizumab (Avastin), according to a new study.

A recent phase III trial showed that the addition of bevacizumab, a monoclonal antibody to vascular endothelial growth factor-A (VEGF), to first-line irinotecan, 5-fluorouracil, and leucovorin (IFL) prolonged survival in patients with metastatic colorectal cancer. Preclinical and clinical studies have indicated that mutations in the Ras/Raf/Mek/Erk pathway--which includes the genes k-ras and b-raf--or inactivation of P53 may modify the effect of anti-VEGF therapies, such as bevacizumab.

To determine whether mutation status of k-ras, b-raf or p53, or P53 expression could predict which colorectal cancer patients were more likely to respond to bevacizumab, William L. Ince, of Genentech, Inc., in South San Francisco, Calif., and colleagues evaluated tumors available from a subset of 295 patients from the recent phase III trial.

The increase in median survival associated with the addition of bevacizumab did not differ by mutation or expression status in any of the biomarkers in the patients. The authors conclude that k-ras, b-raf, and p53 status do not predict patient response to bevacizumab.

Contact: Neil Cohen, Genentech, 650-225-8681, [email protected]

Results of Initial Colorectal Cancer Screening in Large Trial Released

The results of the initial colorectal cancer screening of thousands of participants in the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial found a high acceptance of flexible sigmoidoscopy screening and indicate that the trial's eventual results should approximate those that could be expected from screening the general U.S. population, according to a new study.

The PLCO cancer screening trial is evaluating the effect of screening flexible sigmoidoscopy on colorectal cancer mortality when performed once and then repeated 3 to 5 years later. Joel L. Weissfeld, M.D., M.P.H., of the University of Pittsburgh Cancer Institute, and colleagues report the results from the baseline screening examination, which included more than 77,000 men and women ages 55 to 74 who were enrolled at 10 screening centers.

Nearly 65,000 subjects--83.5% of the participants--underwent flexible sigmoidoscopy screening, and at least one polyp was detected in 15,150 (23.4%) of the participants. Of these participants, nearly three-quarters had follow-up lower endoscopy. Cancer and adenoma detection yields were similar to those in other studies. Given the high acceptance of flexible sigmoidoscopy screening and the observed detection rates in a large, geographically diverse population in which diagnostic follow-up was managed by community practitioners, the authors conclude that the PLCO trial results should approximate those that could be expected from a flexible sigmoidoscopy screening program targeting the general U.S. population.

Contact: Clare Collins, University of Pittsburgh, 412-624-2607, [email protected]

Bone Marrow Transplant Recipients May Be Exposed to Virus Associated With Cancer, Study Finds

It may be possible for people who receive bone marrow transplants to be exposed to human herpesvirus 8 (HHV-8) if they receive a transplant from an infected donor, according to a new study. HHV-8 is a virus associated with Kaposi sarcoma, body cavity lymphomas, and Castleman disease.

Kaposi sarcoma occurs in about 0.2% to 0.5% of patients after solid organ transplantation but is rare among bone marrow transplant recipients. Whether HHV-8 can be transmitted through blood has been uncertain, and it has not been known whether bone marrow transplant recipients can become infected with HHV-8 from their donors.

To investigate the prevalence of HHV-8 infection in bone marrow transplant recipients and donors, Giuseppe Gentile, M.D., of University "La Sapienza" in Rome, and colleagues evaluated blood samples from 187 Italian bone marrow transplant donor"“recipient pairs. Before the transplants, 24 (13%) of the 197 donors and 20 (11%) of the recipients had antibodies to HHV-8 in their blood. After the transplants, 28 (15%) of the recipients had HHV-8 antibodies. Furthermore, of the 167 bone marrow transplant recipients who did not have HHV-8 antibodies at baseline, 19 (11%) had HHV-8 antibodies in their blood after the transplant. Thus, recipients can by infected by HHV-8 through the receipt of bone marrow from an infected donor, but other factors may also contribute to the change from antibody negative to antibody positive status, the authors conclude.

Contact: Giuseppe Gentile, University "La Sapienza", +39 6 85795655, [email protected]

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Journal of the National Cancer Institute