A new study suggests that the body’s ability to repair DNA damage caused by ultraviolet radiation from sunlight may influence the risk of melanoma in people who do not tan easily and who have many unusually large and irregularly shaped moles (called dysplastic nevi).
Dysplastic nevi and low tanning ability are known risk factors for melanoma. Exposure to UV radiation from sunlight is also associated with an increased risk of the disease. Maria Teresa Landi, M.D., Ph.D., of the National Cancer Institute, and colleagues looked at a group of patients in Italy to determine whether the cellular capacity to repair DNA damage is associated with the risk of cutaneous malignant melanoma.
By studying 132 patients with melanoma and 145 control subjects, the authors found that, independent of other risk factors, DNA repair capacity was not associated with an increased risk of melanoma. However, among patients who had low tanning ability or dysplastic nevi, those with a low DNA repair capacity had a higher risk of the disease than those with a high DNA repair capacity. These results are presented in the Jan. 16 issue of the Journal of the National Cancer Institute.
Contact: NCI Press Office, (301) 496-6641
Predictive Value of HPV Testing in Managing Equivocal Pap Tests Improves with Age, Study Shows
Each year, about 50 million Pap tests are taken in the United States, 2 million of which are not entirely normal. Most Pap tests that are not clearly normal show equivocal (aytpical squamous cells of undetermined significance [ASCUS]) or mild (low-grade squamous intraepithelial lesions [LSIL]) abnormalities.
Only about 5% of women with ASCUS and 10% of those with LSIL have a known precursor to cancer, called cervical intraepithelial neoplasia 3 (CIN3). Therefore, referring all women with ASCUS or LSIL for colposcopy (examination of the cervix with a magnifying lens) or biopsy (removal of tissue for microscopic diagnosis) would be expensive, impractical, and anxiety provoking for many healthy women.
Almost all cervical cancers are associated with infection with a specific group of human papillomaviruses (HPV). This has led researchers to investigate whether HPV testing might be useful to select which women with ASCUS or LSIL require further diagnostic tests. The ASCUS/LSIL Triage Study (ALTS) was a randomized clinical trial designed to find more efficient ways to manage women who have ASCUS or LSIL Pap smears.
In the Jan. 16 issue of the Journal of the National Cancer Institute, Mark E. Sherman, M.D., of the National Cancer Institute, and colleagues from the ALTS group demonstrated that HPV testing was highly sensitive for detecting CIN3 or cancer across all ages among women with ASCUS or LSIL. Among women with ASCUS aged 29 years and older, they found that HPV testing would have referred many fewer patients for colposcopy than testing among younger women. Referrals to colposcopy based on the results of a repeat Pap test also declined among older women, but less dramatically than with HPV testing.
This study also demonstrated that measuring the amount of virus in HPV-positive samples did not improve the test’s ability to detect CIN3 and cancer. In addition, this report failed to identify a promising alternative strategy to colposcopy referral for women with LSIL. The authors note that these results may have implications for understanding the cost-effectiveness of different management strategies for cervical cancer.
Contact: NCI Press Office, (301) 496-6641
Two Biomarkers Help Predict Course of Breast Cancer
Measuring levels of two biomarkers, urokinase-type plasminogen activator (uPA) and its inhibitor (PAI-1), in breast cancer patients may help doctors better understand the course of the disease, a new study suggests.
Both uPA and PAI-1 play essential roles in tumor invasion and metastasis. High levels of these proteins are associated with poor prognosis in breast cancer patients. Maxime P. Look and colleagues at the University Hospital Rotterdam, The Netherlands, on behalf of the European Organization for Research and Treatment of Cancer-Receptor and Biomarker Group (EORTC-RBG), reanalyzed individual patient data from more than 8,000 primary breast cancer tumors to confirm the biomarkers’ ability to predict patient outcome. Their results are published in the Jan. 16 issue of the Journal of the National Cancer Institute.
Their analysis found that, apart from lymph node status, high levels of uPA and PAI-1 were the strongest predictors of poor relapse-free survival and poor overall survival. The authors conclude that, for patients with lymph node-negative breast cancer, uPA and PAI-1 measurements in primary tumors may be useful for designing individualized treatment strategies.
Contact: Allard de Jong, University Hospital Rotterdam, (31) 10 4634164, e-mail: adejong@prev.azr.nl
Possible Mechanism Found for Chemotherapy Resistance in Pancreatic Cancer
Pancreatic cancer is often resistant to chemotherapy. A new study suggests that the overexpression of the tumor-suppressor gene pRB may be responsible for the resistance.
The pRB protein prevents apoptotic cell death, which is a cellular process that many chemotherapy drugs initiate to kill the target tumor. Another tumor suppressor protein, p16, may play a role in pancreatic cancer because its expression is inactivated in more than 90% of pancreatic cancers. These two proteins are interdependent; pRB expression is inhibited by p16, and p16 expression is inhibited by pRB. Thomas Plath, Stefan Rosewicz, M.D., and colleagues at Humboldt University, Berlin, tested whether pRB is involved in the resistance to chemotherapy-induced apoptosis.
The authors found that pRB was overexpressed in pancreatic ductal adenocarcinomas but not in other pancreatic malignancies or normal pancreatic tissue. In addition, inhibition of pRB expression in pancreatic cancer cell lines in which p16 expression had been restored was associated with an increase in chemotherapy-induced apoptosis. The authors conclude that overexpression of pRB may allow pancreatic cancer cells to evade chemotherapy-induced apoptosis. Their results are presented in the Jan. 16 issue of the Journal of the National Cancer Institute.
Contact: Stefan Rosewicz, M.D., (49) 30 4505 3733, stefan.rosewicz@charite.de
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