Chemotherapy and thyroid cancer risk: a report from the childhood cancer survivor study.
BACKGROUND
Although ionizing radiation is an established environmental risk factor for thyroid cancer, the effect of chemotherapy drugs on thyroid cancer risk remains unclear. We evaluated the chemotherapy-related risk of thyroid cancer in childhood cancer survivors and the possible joint effects of chemotherapy and radiotherapy.


METHODS
The study included 12,547 five-year survivors of childhood cancer diagnosed during 1970 through 1986. Chemotherapy and radiotherapy information was obtained from medical records, and radiation dose was estimated to the thyroid gland. Cumulative incidence and relative risks were calculated with life-table methods and Poisson regression. Chemotherapy-related risks were evaluated separately by categories of radiation dose.


RESULTS
Histologically confirmed thyroid cancer occurred in 119 patients. Thirty years after the first childhood cancer treatment, the cumulative incidence of thyroid cancer was 1.3% (95% CI, 1.0-1.6) for females and 0.6% (0.4-0.8) for males. Among patients with thyroid radiation doses of 20 Gy or less, treatment with alkylating agents was associated with a significant 2.4-fold increased risk of thyroid cancer (95% CI, 1.3-4.5; P = 0.002). Chemotherapy risks decreased as radiation dose increased, with a significant decrease for patients treated with alkylating agents (P(trend) = 0.03). No chemotherapy-related risk was evident for thyroid radiation doses more than 20 Gy.


CONCLUSIONS
Treatments with alkylating agents increased thyroid cancer risk, but only in the radiation dose range less than 20 Gy, in which cell sparing likely predominates over cell killing.


CONCLUSIONS
Our study adds to the evidence for chemotherapy agent-specific increased risks of thyroid cancer, which to date, were mainly thought to be related to prior radiotherapy.
Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, 6120 Executive Boulevard EPS 7051, MSC 7238, Bethesda, MD 20892, USA. veigal@mail.nih.gov
Lene H S
LH
Veiga
Parveen
P
Bhatti
Cécile M
CM
Ronckers
Alice J
AJ
Sigurdson
Marilyn
M
Stovall
Susan A
SA
Smith
Rita
R
Weathers
Wendy
W
Leisenring
Ann C
AC
Mertens
Sue
S
Hammond
Joseph P
JP
Neglia
Anna T
AT
Meadows
Sarah S
SS
Donaldson
Charles A
CA
Sklar
Debra L
DL
Friedman
Leslie L
LL
Robison
Peter D
PD
Inskip
D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002170:Canada / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008875:Middle Aged; D009381:Neoplasms, Radiation-Induced / Q000453:epidemiology / Q000209:etiology*; D011878:Radiotherapy / Q000009:adverse effects; D012307:Risk Factors; D017741:Survivors; D013964:Thyroid Neoplasms / Q000139:chemically induced / Q000453:epidemiology / Q000209:etiology*; D014481:United States / Q000453:epidemiology; D055815:Young Adult
D000970:Antineoplastic Agents