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JNCI Podcast: Issue 18 Transcript

Issue 18 of the Journal of the National Cancer Institute includes a study and an accompanying editorial on the contribution of clinical breast examination to breast cancer screening and a study and an accompanying editorial on using fecal DNA methylation to detect gastric and colorectal cancers. This issue also includes studies on melanosomes and sensitivity of melanoma cells to chemotherapy; the risk of prostate cancer from high serum insulin levels; and a brief communication that profiles prostate cancer diagnosis and racial disparities in the United States.

Contribution of Clinical Breast Examination to Breast Cancer Screening

Breast cancer detection rates and sensitivity were higher, but so were false-positive rates, among mammography centers that offered clinical breast examination in addition to mammography, according to this study published online August 31.

There is controversy about whether adding clinical breast examination to mammography improves the accuracy of breast screening.

To address this, Anna M. Chiarelli, of the Populations Studies and Surveillance, Cancer Care Ontario, and colleagues compared the accuracy of screening among centers that offered clinical breast examination in addition to mammography with that of centers that offered only mammography.

Using a cohort of more than 290,000 women within the Ontario Breast Screening Program screened between January 2002 and December 2003, the researchers found that the sensitivity of referrals was higher for women who were screened at centers that offered clinical breast examination and mammography than for women who were screened at centers that did not offer clinical breast examination. However, women without cancer who were screened at centers that offered clinical breast examination had a higher false-positive rate than women screened at centers that offered only mammography.

The data suggests that the accuracy of clinical breast examination can be improved in screening programs that offer high-quality clinical breast examinatio

Fecal DNA Methylation Detects Gastric and Colorectal Cancers

A study published online August 21 found that a preliminary evaluation of methylation of two gene promoters in fecal DNA showed promise as a noninvasive method to detect colorectal and gastric cancers.

Because many patients are reluctant to undergo invasive tests for the detection of gastrointestinal cancers, the development of nonintrusive screening tests is desirable. Especially in cancer patients, some cells are sloughed off from the gastrointestinal tract, so small amounts of DNA from these cells present in stool samples can be examined for the presence of cancer biomarkers.

Takeshi Nagasaka, of the Department of Gastroenterological Surgery and Surgical Oncology at the Okayama University of Graduate School of Medicine, and colleagues analyzed methylation of the RASSF2 and SFRP2 gene promoters from 788 primary gastric and colorectal tissue specimens to determine whether methylation patterns could act as stage-dependent biomarkers of gastrointestinal tumorigenesis. Next, a highly-sensitive assay was developed for the detection of these methylation patterns among 296 fecal DNA specimens from patients with colorectal or gastric tumors.

Extensive methylation at these gene promoters was much more likely to be found in advanced gastric tumors and colorectal tumors than in normal tissue. Methylation markers were detected in 57% of gastric cancer patients, 75% of colorectal cancer patients

Melanosome Dynamics and Sensitivity of Melanoma Cells to Chemotherapy

Manipulating the functions of melanosomes—which are the organelles in pigment-producing cells—may enhance the activity of anticancer drugs used against melanoma, according to this study published online August 24.

To examine the role of melanosomes in the sensitivity of malignant melanoma to chemotherapeutic agents, Kevin Chen, Vincent Hearing, Michael M. Gottesman, of the Laboratory of Cell Biology at the National Cancer Institute in Bethesda, Md., and colleagues compared pigmentation and melanosome developmental stage, number, and cellular structures in melanoma cell lines in response to treatment with chemotherapeutic agents.

The authors found that late-stage melanosomes that were damaged and thus could not trap metabolites were toxic to melanoma cells. They also found that melanoma cells that survived cisplatin treatment had more stage II-III functional melanosomes—also known as early melansomes because they have not initiated melanin synthesis—than untreated melanoma cells. In addition, when melanosomes were reverted to relatively early stages, the melanoma cells became more resistant to cisplatin.

The authors said that manipulation of melanosome status either by cytotoxic or by noncytotoxic drugs opens therapeutic avenues and raises the prospect of successfully treating pigment-producing cell-related diseases and, in particular, highly intractable malignant melanoma

High Serum Insulin Levels and Risk of Prostate Cancer

Elevated insulin levels in the normal range appear to be associated with an increased risk of prostate cancer, according to a new study published online August 21.

Insulin-like growth factors appear to be involved in the development of prostate cancer, but the relationship between circulating insulin levels and prostate cancer risk has been unclear.

Demetrius Albanes, of the Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics at the National Cancer Institute in Bethesda, Md., and colleagues investigated the relationship of the level of serum insulin and glucose, as well as surrogate indices of insulin resistance, to the development of prostate cancer. Researchers conducted a prospective case–cohort study nested within a cancer prevention study of Finnish men. Levels of insulin were determined in fasting serum that had been collected 5-12 years before diagnosis of prostate cancer.

The authors found that when subjects in the second through fourth quartiles of serum insulin concentration were compared with those in the first or lowest quartile, higher insulin levels within the normal range were associated with statistically significantly increased risk of prostate cancer. Risk was not associated with serum glucose concentration.

Prostate cancer: Racial disparity gap narrows; men diagnosed at younger age

The racial disparity in prostate cancer stage at diagnosis has decreased statistically significantly over time, according to a brief communication published online August 27.

By analyzing data from the Surveillance, Epidemiology, and End Results, or SEER, program, Grace L. Lu-Yao, of The Cancer Institute of New Jersey and the University of Medicine and Dentistry of New Jersey in New Brunswick, and colleagues also found that more men were diagnosed with prostate cancer at a younger age and earlier stage in 2004–2005 than in earlier years.

The researchers used SEER data to generate a contemporary profile of prostate cancer patients by comparing patient characteristics of a 2004–2005 population with those of patients diagnosed in 1988–1989 and 1996–1997. They also compared the characteristics of the 2004–2005 patient population with those of participants in a randomized trial of radical prostatectomy versus watchful waiting that showed better survival for patients aged 65 years or younger in the radical prostatectomy group.

According to the study, incidence of stage T3 or T4 cancer at diagnosis has decreased in both blacks and whites, and the racial disparity in cancer state at diagnosis has decreased over time. Compared with patients in the trial, patients in the SEER population had a lower prostate-specific antigen level and earlier stage cancer at diagnosis.