Other highlights in the March 11 JNCI

Radiation Exposure In Utero and in Young Children Increases Adult Cancer Risk

Radiation exposure before birth or during early childhood increased the risk of adult solid cancers, according to a study of survivors of the Hiroshima and Nagasaki bombings.

It is known that radiation exposure during fetal development increases the risk of childhood cancers and that exposure during early childhood increases the risk of adult-onset cancers. However it was not known if radiation exposure to the fetus increases the risk of adult cancers.

To find out, Dale Preston, Ph.D., of the Hirosoft International Corporation in Eureka, Calif., and colleagues at the Radiation Effects Research Foundation in Hiroshima, Japan, calculated the excess risk of solid cancers in adult survivors of the Hiroshima and Nagasaki bombings, relative to non-exposed populations.

Of the 2,452 study participants who were exposed to radiation before birth, 94 have developed adult cancers, as did 649 of the 15,388 individuals who were exposed between birth and six years of age. By age 50, the excess relative risk for those exposed before birth was 1.0 per Sv (a unit for measuring radiation exposure), and for those exposed as young children, it was 1.7 Sv at age 50.

The researchers note that the overall risk of solid cancers increases with age, and so continuing to follow the study participants as they age will be important. Also, the investigators only considered solid cancers, and did not examine the rate of blood cancers, such as leukemia.

“The present data suggested that increases in risks of adult-onset cancer among those exposed to radiation in utero may be smaller than for those exposed in early childhood,” the authors write. That said, these data may be important when considering the public health risks of medical and occupational radiation exposure for pregnant women.

Contact: Dale Preston, preston@hirosoft.net, (707) 476-8648 or (707) 531-4883; or Roy Shore, chief of research, Radiation Effects Research Foundation, shore@rerf.or.jp, +81-82-262-3131

Anchoring Protein Variant Associated with Increased Breast Cancer Risk

Individuals who carry a rare genetic variant have an increased risk of developing breast cancer over their lifetimes, compared with those who do not have the variant.

Few genes have been found to have a large impact on the risk of familial breast cancer, and researchers expect that most breast cancers are influenced by the combined effects of multiple genes, each of which has a small impact on its own. One of those genes may be AKAP9.

To determine whether a rare sequence variant of the AKAP9 gene increases the risk of breast cancer, Barbara Burwinkel, Ph.D., of the German Cancer Research Center in Heidelberg and colleagues compared the frequency of the variant in 9,523 breast cancer patients with its frequency in 13,770 healthy control subjects from a large international collaboration project.

The team found that individuals who carry two copies of the rare variant have a 17 percent increased relative risk of developing breast cancer compared with those who carry two copies of the normal sequence. For those individuals who carry one copy of the rare variant and one copy of the normal sequence, their relative risk increased 10 percent over their lifetime.

“It is also of interest that this variant has previously been found to be associated with colorectal and lung cancer risk,” the authors write.

Contact: Stefanie Seltmann, presse@dkfz.de, 0049-6221-42-2854

Sexual Activity and Marijuana Use Associated with HPV-Positive Head and Neck Cancer

The risk factors for human papillomavirus (HPV) type 16-associated head and neck cancer are different from those associated with head and neck cancers that do not express HPV. The two types of cancers should be considered distinct malignancies.

Scientists have recently discovered that HPV-16, which is known to cause cervical cancer, can also lead to head and neck cancers. It was not clear, however, whether previously identified risk factors for head and neck cancer, such as tobacco smoking and alcohol consumption, apply to the malignancies caused by the virus.

To find out, Maura Gillison, M.D., Ph.D., of the Johns Hopkins Kimmel Comprehensive Cancer Center in Baltimore and colleagues conducted a case-control study with 240 head and neck cancer patients and 322 matched control subjects. The team collected behavioral information using a computer-assisted self-interview technique. They also examined tumor samples from each patient to determine whether the cancer expressed HPV-16.

A total of 92 cancers (38 percent) were HPV-16 positive. HPV-positive cancers were associated with increasing numbers of oral sexual partners and with increased marijuana use. Smoking, alcohol consumption, and poor oral hygiene were not associated with HPV-positive cancers, but were associated with HPV-negative head and neck cancers.

“Our data support the existence of at least two etiologically distinct pathways for [head and neck cancer] pathogenesis, one mediated by tobacco and alcohol and the other by HPV,” the authors write.

Contact: Vanessa Wasta, media relations, Sidney Kimmel Comprehensive Cancer Center, wastava@jhmi.edu, (410) 955-1287

Overexpression of an Inflammatory Marker May Be Associated with an Increased Risk of Breast Cancer

Expression of the inflammatory protein, cyclooxygenase-2 (COX-2), in benign breast biopsy samples may be associated with an increased risk of a breast cancer diagnosis in the future.

Many breast biopsies uncover non-cancerous but abnormal tissue growth patterns, including atypical hyperplasia. Although women with such a diagnosis are at a higher risk of developing breast cancer in the future, not all of them will do so. Identifying ways to distinguish precancerous lesions from ones that will remain benign is important. One marker that has been associated with cancer development in animal models and some human cancers is COX-2.

Lynn Hartmann, M.D., of the Mayo Clinic in Rochester, Minn., and colleagues tested archival biopsy samples for expression of COX-2 and collected information on subsequent breast cancer diagnoses from medical records and a study questionnaire. The risk of developing breast cancer was compared with that of the general population.

A total of 235 women participated in the study, each of whom had been diagnosed with atypical hyperplasia between 1967 and 1991. After a median follow-up of 15 years, 41 women had developed breast cancer. The risk of a breast cancer diagnosis increased with the intensity of COX-2 expression in the initial biopsy sample. The trend of increasing risk with increasing expression intensity was of borderline statistical significance. For those with the highest level of expression, the risk rose 5.66-fold, from an expected 1.6 cases of breast cancer to nine observed cases.

These data, together with other studies in breast cancer, suggest COX-2 “may be a relevant target for chemoprevention strategies,” the authors write.

Contact: Elizabeth Zimmermann, public affairs office, Mayo Clinic Cancer Center, (507)266-0810 or (507) 284-5005, newsbureau@mayo.edu

Also in the March 11 JNCI:

• http://www.eurekalert.org/emb_releases/2008-03/jotn-cd030608.php
• http://www.eurekalert.org/emb_releases/2008-03/jotn-hc030608.php