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Genetic variations associated with treatment response for childhood leukemia
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CHICAGO—Children with acute lymphoblastic leukemia with certain genetic variations can have a different response to anti-cancer treatment than other patients, according to a study in the January 28 issue of JAMA.



Pediatric acute lymphoblastic leukemia (ALL) cure rates have increased from less than 10 percent in the 1960s to more than 80 percent today, although considerable unexplained individual variability exists in treatment response, according to background information in the article.

Jun J. Yang, Ph.D., of St. Jude Children's Research Hospital, Memphis, Tenn., and colleagues conducted a study to identify genetic factors that may affect treatment response in ALL. The researchers tested single nucleotide polymorphisms (SNPs; genetic variations) for their association with minimal residual disease (MRD) at the end of initial chemotherapy in two groups (totaling 487 children) treated for newly diagnosed ALL. Patients were enrolled between 1994 and 2006, with the last follow-up in 2006.

The researchers found that there were 102 SNPs associated with MRD in both groups. All 102 SNPs remained significantly associated with MRD after adjustment for race, sex, leukocyte (a type of blood cell) count at diagnosis, age, and ALL subtype. Of the 102 SNPs, 21 were significantly associated with hematologic (blood-related) relapse. Of 102 SNPs, 21 were also associated with antileukemic drug disposition, generally linking MRD eradication with greater drug exposure. The researchers found that a high proportion (63 of 102 SNPs [61.7 percent]) also were associated with early response, relapse risk, or antileukemic drug disposition.

"Although the acquired genetic characteristics of tumor cells play a critical role in drug responsiveness, our results show that inherited genetic variation of the patient also affects effectiveness of anticancer therapy, and that genome-wide approaches can identify novel and yet plausible pharmacogenetic variation. Such variation may be factored into treatment decisions in the future by placing additional emphasis on optimizing drug delivery to overcome host genetic variation, in addition to the current emphasis on tumor genetic variation," the authors conclude.
(JAMA. 2009;301[4]:393-403. Available pre-embargo to the media at

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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Embargoed for Release: 3:00 p.m. CT, Tuesday, January 27, 2009
Media Advisory: To contact Kevin C. Oeffinger, M.D., call Courtney DeNicola at 646-227-3633 or email denicolc{at} . To contact editorial co-author Aliki J. Taylor, M.D., M.P.H., Ph.D., email A.J.Taylor{at} .

Many Women Who Survived Childhood Cancer Do Not Undergo Recommended Breast Cancer Screening

CHICAGO—Despite recommendations and being at an increased risk of breast cancer, most young women who were treated with chest radiation for a childhood cancer do not undergo appropriate mammography screening, according to a study in the January 28 issue of JAMA.

Women treated with chest radiation for a pediatric malignancy face a significantly increased risk of breast cancer at a young age. "The risk of breast cancer begins to increase as early as 8 years after radiation and the median [midpoint] age of breast cancer diagnosis ranges from 32 to 35 years," the authors write. By age 45 years, it is estimated that from 12 percent to 20 percent of women treated with moderate- to high-dose chest radiation will be diagnosed with breast cancer.

Experts recommend annual screening mammography for women exposed to moderate- to high-dose chest radiation, starting at 25 years of age or 8 years after radiation, whichever occurs last. It is estimated that in the United States there are approximately 20,000 to 25,000 women who are 25 years or older and were treated for a pediatric malignancy with moderate- to high-dose chest radiation. There is limited published information regarding the breast cancer screening practices of women who were treated with chest radiation for a childhood malignancy, according to background information in the article.

Kevin C. Oeffinger, M.D., of Memorial Sloan-Kettering Cancer Center, New York, and colleagues conducted a study that included 625 women, age 25 through 50 years, who had survived pediatric cancer, had been treated with chest radiation and were participating in the Childhood Cancer Survivor Study (CCSS), a North American group of long-term survivors diagnosed from 1970-1986. Participants received a 114-item questionnaire. Comparisons were made with similarly aged pediatric cancer survivors not treated with chest radiation (n = 639) and the siblings of the CCSS group (n = 712). Of 1,976 cancer survivors and siblings who were contacted, 87.9 percent participated.

Among women age 25 through 39 years who had received chest radiation therapy (RT), 36.5 percent reported a screening mammogram within the past 2 years; 47.3 percent had never had a mammogram; and only 23.3 percent had a screening or diagnostic mammogram within the previous year.

Women age 40 through 50 years who had received chest RT were more likely to report mammography than their younger counterparts, with 76.5 percent reporting a screening mammogram within the past 2 years compared with 70.0 percent for the group without chest RT and 67.0 percent for the CCSS sibling group. Only 52.6 percent of women in this age group with chest RT had regular screening (at least 2 mammograms within 4 years). This was not significantly higher than for

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