Journal Article Bladder and Kidney Cancer Following Cyclophosphamide Therapy for Non-Hodgkin's Lymphoma Get access Lois B. Travis, Lois B. Travis Epidemiology and Biostatistics Program, Division of Cancer Etiology, National Cancer InstituteBethesda, Md Search for other works by this author on: Oxford Academic PubMed Google Scholar Rochelle E. Curtis, Rochelle E. Curtis Epidemiology and Biostatistics Program, Division of Cancer Etiology, National Cancer InstituteBethesda, Md Search for other works by this author on: Oxford Academic PubMed Google Scholar Bengt Glimelius, Bengt Glimelius University HospitalUppsala, Sweden Search for other works by this author on: Oxford Academic PubMed Google Scholar Eric J. Holowaty, Eric J. Holowaty The Ontario Cancer Treatment and Research FoundationToronto, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar Flora E. Van Leeuwen, Flora E. Van Leeuwen The Netherlands Cancer InstituteAmsterdam Search for other works by this author on: Oxford Academic PubMed Google Scholar Charles F. Lynch, Charles F. Lynch The University of IowaIowa City Search for other works by this author on: Oxford Academic PubMed Google Scholar Anton Hagenbeek, Anton Hagenbeek The Dr. Daniel den Hoed Cancer CenterRoterdam, The Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar Marilyn Stovall, Marilyn Stovall The University of Texas M. D. Anderson Cancer CenterHouston Search for other works by this author on: Oxford Academic PubMed Google Scholar Peter M. Banks, Peter M. Banks University of Texas Health Sciences CenterSan Antonio Search for other works by this author on: Oxford Academic PubMed Google Scholar Johanna Adami, Johanna Adami University HospitalUppsala, Sweden Search for other works by this author on: Oxford Academic PubMed Google Scholar ... Show more Mary K. Gospodarowicz, Mary K. Gospodarowicz Princess Margaret HospitalToronto Search for other works by this author on: Oxford Academic PubMed Google Scholar Sholom Wacholder, Sholom Wacholder Epidemiology and Biostatistics Program, Division of Cancer Etiology, National Cancer InstituteBethesda, Md Search for other works by this author on: Oxford Academic PubMed Google Scholar Peter D. Inskip, Peter D. Inskip Epidemiology and Biostatistics Program, Division of Cancer Etiology, National Cancer InstituteBethesda, Md Search for other works by this author on: Oxford Academic PubMed Google Scholar Margaret A. Tucker, Margaret A. Tucker Epidemiology and Biostatistics Program, Division of Cancer Etiology, National Cancer InstituteBethesda, Md Search for other works by this author on: Oxford Academic PubMed Google Scholar John D. Boice, Jr John D. Boice, Jr Epidemiology and Biostatistics Program, Division of Cancer Etiology, National Cancer InstituteBethesda, Md Correspondence to: Lois B. Travis, M.D., National Institutes of Health, Executive Plaza North, Suite 408, Bethesda, MD 20892 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 7, 5 April 1995, Pages 524–531, https://doi.org/10.1093/jnci/87.7.524 Published: 05 April 1995 Article history Received: 24 August 1994 Revision received: 07 December 1994 Accepted: 20 January 1995 Published: 05 April 1995
Abdominal radiotherapy for testicular cancer (TC) increases risk for second stomach cancer, although data on the radiation dose-response relationship are sparse.
Second cancer is the leading cause of death in long-term survivors of Hodgkin disease (HD), with exceptionally high risks of breast cancer among women treated at a young age. Quantitative associations between radiotherapy dose delivered to the breast and administered chemotherapy have not been reported to date in large series, nor has the influence of ovarian exposures on subsequent risk.
Objective
To quantify the long-term risk of breast cancer associated with use of radiotherapy and chemotherapy to treat young women with HD.
Design, Setting, and Subjects
Matched case-control study of breast cancer within a cohort of 3817 female 1-year survivors of HD diagnosed at age 30 years or younger, between January 1, 1965, and December 31, 1994, and within 6 population-based cancer registries. The study was conducted March 1, 1996, through September 30, 1998.
Main Outcome Measures
Relative risk (RR) of breast cancer associated with radiation dose delivered to site of breast cancer or to ovaries and with cumulative dose of alkylating agents.
Results
Breast cancer occurred in 105 patients with HD who were matched to 266 patients with HD but without breast cancer. A radiation dose of 4 Gy or more delivered to the breast was associated with a 3.2-fold (95% confidence interval [CI], 1.4-8.2) increased risk, compared with the risk in patients who received lower doses and no alkylating agents. Risk increased to 8-fold (95% CI, 2.6-26.4) with a dose of more than 40 Gy (P<.001 for trend). Radiation risk did not vary appreciably by age at exposure or reproductive history. Increased risks persisted for 25 or more years following radiotherapy (RR, 2.3; 95% CI, 0.5-16.5;P= .03 for trend with dose). Treatment with alkylating agents alone resulted in a reduced risk (RR, 0.6; 95% CI, 0.2-2.0) of breast cancer, and combined alkylating agents and radiotherapy in a 1.4-fold (95% CI, 0.6-3.5) increased risk. Risk of breast cancer decreased with increasing number of alkylating agent cycles (P= .003 for trend). Risk also was low (RR, 0.4; 95% CI, 0.1-1.1) among women who received 5 Gy or more delivered to ovaries compared with those who received lower doses.
Conclusions
Hormonal stimulation appears important for the development of radiation-induced breast cancer, as evidenced by the reduced risk associated with ovarian damage from alkylating agents or radiation. The high radiation-related risk, which did not diminish at the highest doses or the longest follow-up, however, suggests the need for lifetime surveillance and programs of patient and public awareness.
To observe the association between socioeconomic status (SES) and cancer incidence in a cohort of Canadians.Cases of primary malignant cancer (83,666) that arose in metropolitan Toronto, Ont., from 1986 to 1993 were ascertained by the Ontario Cancer Registry and linked by residence at the time of diagnosis to a census-based measure of SES. Socioeconomic quintile areas were then compared by cancer incidence.Significant associations between SES and cancer incidence in the hypothesized direction--greater incidence in low-income areas--were observed for 15 of 23 cancer sites.These findings, together with the recently observed consistent pattern of significant associations between SES and cancer survival in the United States and the equally consistent pattern of nonsignificant associations in Canada, support the notion that differences in cancer incidence alone explain the observed cancer mortality differentials by SES in Canada. The cancer mortality differential by SES observed in the United States is probably a function of differences in both incidence and length of survival, whereas in Canada such mortality differentials are more likely to be merely a function of differences in incidence by SES. This pattern of associations primarily implicates differences in the 2 health care systems; specifically, the more egalitarian access to preventive, investigative and therapeutic services available in the single-payer Canadian system.
We sought to determine whether the -6 exon 13 T>C polymorphism in the DNA mismatch repair gene hMSH2 modulates susceptibility to acute myeloid leukemia after therapy and particularly after O(6)-guanine alkylating chemotherapy. We also determined the extent of microsatellite instability (MSI) in therapy-related acute myeloid leukemia (t-AML) as a marker of dysfunctional DNA mismatch repair.Using a novel restriction fragment length polymorphism, verified by direct sequencing, we have genotyped 91 t-AML cases, 420 de novo acute myeloid leukemia cases, and 837 controls for the hMSH2 -6 exon 13 polymorphism. MSI was evaluated in presentation bone marrow from 34 cases using the mononucleotide microsatellite markers BAT16, BAT25, and BAT26.Distribution of the hMSH2 -6 exon 13 polymorphism was not significantly different between de novo acute myeloid leukemia cases and controls, with heterozygotes and homozygotes for the variant (C) allele representing 12.2 and 1.6%, respectively, of the control population. However, the variant (C) hMSH2 allele was significantly overrepresented in t-AML cases that had previously been treated with O(6)-guanine alkylating agents, including cyclophosphamide and procarbazine, compared with controls (odds ratio, 4.02; 95% confidence interval, 1.40-11.37). Thirteen of 34 (38%) t-AML cases were MSI positive, and 2 of these 13 cases were homozygous for the variant (C) allele, a frequency substantially higher than in the control population.Association of the hMSH2 -6 exon 13 variant (C) allele with leukemia after O(6)-guanine alkylating agents implicates this allele in conferring a nondisabling DNA mismatch repair defect with concomitant moderate alkylation tolerance, which predisposes to the development of t-AML via the induction of DNA mismatch repair-disabling mutations and high-grade MSI. Homozygosity for the hMSH2 variant in 2 of 13 MSI-positive t-AML cases provides some support for this model.
To describe the patterns of initial management of node-negative breast cancer in Ontario and British Columbia and to compare the characteristics of the patients and tumours and of the physicians and hospitals involved in management.Retrospective, population-based, cohort study.All 942 newly diagnosed cases of node-negative breast cancer in 1991 in British Columbia and a random sample of 938 newly diagnosed cases in Ontario in the same year.Number and proportion of patients with newly diagnosed node-negative breast cancer who received breast-conserving surgery (BCS) or mastectomy and who received radiation therapy after BCS.BCS was used in 413 cases (43.8%) in British Columbia and in 634 cases (67.6%) in Ontario (p < 0.001). After BCS, radiation therapy was received by 378 patients (91.5% of those who had undergone BCS) in British Columbia and 479 patients (75.6% of those who had undergone BCS) in Ontario (p < 0.001). In both provinces, lower patient age, smaller tumour size, a noncentral unifocal tumour, absence of extensive ductal carcinoma in situ and initial surgery by a surgeon with an academic affiliation were associated with greater use of BCS. Lower patient age and larger tumour size were associated with greater use of radiation therapy after BCS in both provinces.Patient, tumour and physician factors are associated with the choice of initial management of breast cancer in these two Canadian provinces. However, the differences in management between the two provinces are only partly explained by these factors. Other possible explanations, such as the presence of provincial guidelines, differences in the organization of the health care system or differences in patient preference, require further research.
We examined the differential effects of the supply of physicians on care for breast cancer in Ontario and California. We then used criteria for optimum care for breast cancer to estimate the regional needs for the supply of physicians.Ontario and California registries provided 951 and 984 instances of breast cancer diagnosed between 1998 and 2000 and followed until 2006. These cohorts were joined with the supply of county-level primary care physicians (PCPs) and specialists in cancer care and compared on care for breast cancer.Significant protective PCP thresholds (7.75 to = 8.25 PCPs per 10 000 inhabitants) were observed for breast cancer diagnosis (odds ratio [OR] 1.62), receipt of adjuvant radiotherapy (OR 1.64) and 5-year survival (OR 1.87) in Ontario, but not in California. The number of physicians seemed adequate to optimize care for breast cancer across diverse places in California and in most Ontario locations. However, there was an estimated need for 550 more PCPs and 200 more obstetrician-gynecologists in Ontario's rural and small urban areas. We estimated gross physician surpluses for Ontario's 2 largest cities.Policies are needed to functionally redistribute primary care and specialist physicians. Merely increasing the supply of physicians is unlikely to positively affect the health of Ontarians.
