Factors influencing mutation at the hprt locus in T-lymphocytes: women treated for breast cancer.
Forty-nine women with breast cancer were enrolled in a prospective, longitudinal study of the genetic damage caused by treatment. Assays of mutant frequency at the hprt locus in peripheral blood lymphocytes were performed at approximately 6-month intervals for 2 years. Treatment consisted of surgery alone or additional tamoxifen, radiotherapy, or chemotherapy in various combinations. At 6 months, there was an elevation of mean mutant frequency compared to initial values (P = 0.004) which persisted for as many as 2 years. A significant elevation at 6 months occurred only in the group of women who received combination chemotherapy (P = 0.005). Within this group, 5 of 15 patients had striking elevations of mutant frequency following chemotherapy (greater than 3 SD). Three of these 5 women had serum folate levels in the deficient range, while only one of 9 patients with lesser responses to chemotherapy were folate deficient. The change in mutant frequency after chemotherapy was inversely related to serum folate levels (P = 0.05) and to the number of years of smoking cigarettes (P = 0.01). We conclude that of the various modalities used to treat breast cancer, only chemotherapy was accompanied by a high risk of somatic mutation. A subset of patients manifested substantial increases in mutant frequency, often in association with low serum folate levels.
Branda
R F
RF
Department of Medicine, University of Vermont, Burlington 05401.
O'Neill
J P
JP
Sullivan
L M
LM
Albertini
R J
RJ
D000970:Antineoplastic Agents / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000628:therapy*; D003131:Combined Modality Therapy; D005260:Female; D005492:Folic Acid / Q000097:blood; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D016296:Mutagenesis; D011446:Prospective Studies; D011878:Radiotherapy / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects; D013601:T-Lymphocytes / Q000502:physiology*
D000970:Antineoplastic Agents; D005492:Folic Acid; D007041:Hypoxanthine Phosphoribosyltransferase