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Summary of Vol 102 Issue 3 Transcript

Hi and welcome to the JNCI podcast, a production of the Journal of the National Cancer Institute. I’m Steve Graff, JNCI’s assistant news and media editor, and I’ll be taking you through issue 3.

All that in more detail coming up next…

First up: a commentary and article in this issue summarizes latest research questions that came out of last fall’s NIH state-of-the-science conference on ductal carcinoma in situ. Also in this issue, researchers found that a Chinese herbal product is associated with the risk of urinary tract cancer. Other studies involve SNPs in C-reactive protein and cancer risk and a nationwide cohort study that investigated sexual defects in boys and testicular cancer risk. Also, a commentary looked at design issues of randomized clinical trials with biomarkers, and in the issue’s last study, researchers investigated risk of colorectal, endometrial, and Lynch syndrome cancer for people with the germ-line MSH6 mutation.

An article and commentary published online January 13 review available data on diagnosis and management of ductal carcinoma in situ, and offer recommendations for the field. These include identification of better risk stratification methods, consideration of the elimination of the word “carcinoma” from the name, and further investigation into whether imaging technology and guidelines can be modified to focus on high-risk lesions.

The commentary is the conference statement from the National Institutes of Health state-of-the-science conference on DCIS. At the conference, speakers and panel members focused on five questions that tackled incidence, risk factors, screening, prognostic factors, and treatment of DCIS. The commentary provides a summary of the answers to those questions based on available research data, input from conference participants, and the panel’s assessment.

The article by Beth A. Virnig, of the University of Minnesota School of Public Health, in Minneapolis, and colleagues is a review of literature on DCIS research from 1965 through January 2009 and was generated for the conference to serve as a background paper.

Virnig covers the five questions discussed at the conference but also highlights areas that need further investigation: associations between mammography use and DCIS incidence and the modification of imaging and treatment guidelines to focus on clinically relevant tumors.

Dr. Joann Elmore, of the University of Washington and panel chair of the conference spoke this JNCI this month and gave her insight on the issue surrounding DCIS.

The carcinogen aristolochic acid, which was found in many prescribed Chinese herbal products is associated with an increased risk of urinary tract cancer, according to a new study published online December 21.

Many countries, such as Taiwan, have banned products containing aristolochic acid because of clinical cases of urothelial cancer in association with aristolochic acid use. However, no such associations, to the authors’ knowledge, have been documented in herbal products containing aristolochic acid.

To examine this association, Jung-Der Wang, of the National Taiwan University, and colleagues conducted a population-based case–control study of Taiwanese patients newly diagnosed with urinary tract cancer from January 1, 2001, to December 31, 2002. They also looked at a random sample of the entire insured population from January 1, 1997, to December 31, 2002. There were 4,594 case patients and 174,701 control subjects in the final analysis. The authors examined the association between having been prescribed Mu Tong, an herb that contains aristolochic acid, and urinary tract cancer using data from the National Health Insurance reimbursement database.

Having been prescribed more than 60 g of Mu Tong, or consumption of an estimated amount of more than 150 mg of aristolochic acid was associated with an increased risk of urinary tract cancer in a dose–dependent manner. The increased risk was independent of arsenic exposure, which is another risk factor for urinary tract cancer.

According to a new brief communication published online January 7, gene variants associated with increased circulating levels of C-reactive protein, a marker of inflammation, are not associated with an increased risk of cancer.

Stig E. Bojesen, of the Copenhagen University Hospital in Denmark, and colleagues used a Mendelian randomization design to test whether C-reactive protein polymorphisms were associated with increased circulating plasma C-reactive protein levels and to determine whether this increase was associated with cancer. The study population included about 10,000 participants in a prospective study and about 36,000 in a cross-sectional study of the adult general population of Denmark, all of whom where genotyped for C-reactive protein single-nucleotide polymorphisms.

The researchers found that variants in the C-reactive protein gene were associated with altered plasma levels of C-reactive protein but did not find an association between these gene variants and an increased risk of cancer.

In an accompanying editorial, Paolo Boffetta, of the International Prevention Research Institute, in France said that the study an elegant example of how genetic variants that have a functional impact can be used to explore associations between environmental factors and disease.

A randomized biomarker-stratified design, which uses the biomarker to guide analysis but not treatment assignment, provides a rigorous assessment of the utility of a potential biomarker for guiding therapy, according to a commentary published online January 14,

In the commentary, Boris Freidlin, of the National Cancer Institute in Bethesda, Md., and colleagues discuss both advantages and disadvantages of commonly used randomized trial designs, including biomarker-stratified, enrichment, and biomarker-strategy designs.

According to the authors, clinical biomarker tests will play an important role in achieving personalized medicine for cancer patients.

Based on a comprehensive review of the three designs, the researchers concluded that biomarker-stratified designs were usually best, when feasible, because they show complete information on the relationship between treatment effect and the biomarker. In this design, patients are randomly assigned regardless of biomarker status, but the analysis is centered on the relationship between the biomarker and the effect of the treatment.

According to a new study published online December 21, boys with the sexual birth defects known as hypospadias and cryptorchidism are at risk for developing testicular germ cell cancer, but their relatives are not.

Although hypospadias, the birth defect that involves an abnormally-placed urinary opening, and cryptorchidism, the lack of descension of one or both testes in the scrotal sac, are associated with a risk of developing testicular germ cell cancer, it was unclear whether all three were part of an inheritable dysgenesis syndrome.

To study this relationship, Tine H. Schnack, of the Statens Serum Institute, in Copenhagen, and colleagues identified over 2 million men born since 1953. They were followed from April 1968 through May 2008. First-, second-, and third-degree relatives were identified in the Danish Family Relations Database; cryptorchidism and hypospadias patients were identified in the Danish Hospital Discharge Register; and testicular germ cell cancer patients were identified in the Danish Cancer Register.

Men with a personal history of cryptorchidism or hypospadias had an increased relative risk of developing testicular germ cell cancer, but their relatives did not. A total of 5,441 patients developed testicular germ cell cancer.

People carrying the germ-line MSH6 mutation are at high risk by age 80 years for colorectal and endometrial cancers and any cancer associated with Lynch syndrome, according to a new study published online December 22.

It is known that mutations in MSH6 account for 10%-20% of Lynch syndrome, which causes colorectal and other cancers, but less is know about the cumulative cancer risks for mutation carriers.

In this study, members of the Colon Cancer Family Registry identified 113 families of MSH6 mutation carriers from five countries who were identified through family cancer clinics and population-based cancer registries. Mutation status, sex, age, and histories of cancer, polypectomy, and hysterectomy were sought from 3,104 of their relatives.

The researchers determined precise estimates of both absolute and relative cancer risks for people who carry the mutation. Compared with incidence for the general population, MSH6 mutation carriers had an eight-fold increased incidence of colorectal cancer. Women who were MSH6 mutation carriers had a 26-fold increased incidence of endometrial cancer and a six-fold increased incidence of other cancers associated with Lynch syndrome.

That’s it for this edition of the JNCI podcast. Check out this month’s JNCI interview with Dr. Joann Elmore, of the University of Washington,who discusses the recent JNCI commentary and article on DCIS.

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I’m Steve Graff, and thanks for listening…