Roles of radiation dose and chemotherapy in the etiology of stomach cancer as a second malignancy.
OBJECTIVE
To evaluate the roles of radiation dose, chemotherapy, and other factors in the etiology of stomach cancer in long-term survivors of testicular cancer or Hodgkin lymphoma.


METHODS
We conducted a cohort study in 5,142 survivors of testicular cancer or Hodgkin lymphoma treated in the Netherlands between 1965 and 1995. In a nested case-control study, detailed information on treatment, smoking, gastrointestinal diseases, and family history was collected for 42 patients with stomach cancer and 126 matched controls. For each subject, the mean radiation dose to the stomach was estimated. Relative risks (RRs) of stomach cancer and the radiation-related excess relative risk (ERR) per gray were calculated by conditional logistic regression analysis.


RESULTS
The risk of stomach cancer was 3.4-fold increased compared with the general population. The risk increased with increasing mean stomach dose (p for trend, <0.001), at an ERR of 0.84 per Gy (95% confidence interval [CI], 0.12-15.6). Mean stomach doses of more than 20 Gy were associated with a RR of 9.9 (95% CI, 3.2-31.2) compared with doses below 11 Gy. The risk was 1.8-fold (95% CI, 0.8-4.4) increased after chemotherapy and 5.4-fold (95% CI, 1.2-23.9) increased after high doses of procarbazine (>or=13,000 mg) vs. <10,000 mg. The RR of smoking more than 10 cigarettes per day vs. no smoking was 1.6 (95% CI, 0.6-4.2).


CONCLUSIONS
Stomach cancer risk is strongly radiation dose dependent. The role of chemotherapy, particularly of procarbazine and related agents, needs further study, because of the relatively small numbers of chemotherapy-treated subjects.
van den Belt-Dusebout
Alexandra W
AW
Department of Epidemiology, the Netherlands Cancer Institute, Amsterdam, the Netherlands.
Aleman
Berthe M P
BM
Besseling
Gijs
G
de Bruin
Marie L
ML
Hauptmann
Michael
M
van 't Veer
Mars B
MB
de Wit
Ronald
R
Ribot
Jacques G
JG
Noordijk
Evert M
EM
Kerst
J Martijn
JM
Gietema
Jourik A
JA
van Leeuwen
Flora E
FE
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D016022:Case-Control Studies; D015331:Cohort Studies; D003131:Combined Modality Therapy / Q000009:adverse effects; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005767:Gastrointestinal Diseases; D006689:Hodgkin Disease / Q000188:drug therapy / Q000532:radiotherapy; D006801:Humans; D008297:Male; D008466:Mechlorethamine / Q000008:administration & dosage; D008875:Middle Aged; D009381:Neoplasms, Radiation-Induced / Q000209:etiology*; D016609:Neoplasms, Second Primary / Q000139:chemically induced / Q000209:etiology*; D009426:Netherlands; D011241:Prednisone / Q000008:administration & dosage; D011344:Procarbazine / Q000008:administration & dosage; D011879:Radiotherapy Dosage; D012044:Regression Analysis; D012306:Risk; D012907:Smoking / Q000009:adverse effects; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000209:etiology*; D017741:Survivors; D013736:Testicular Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D014750:Vincristine / Q000008:administration & dosage; D055815:Young Adult
D011344:Procarbazine; D008466:Mechlorethamine; D014750:Vincristine; D011241:Prednisone