Cancer risks after diagnostic doses of 131I with special reference to thyroid cancer

Between 1951 and 1969 a total of 35,074 patients less than 75 years of age (mean = 44 years) were examined with diagnostic doses of 131I. The mean administered activity of 131I was 52 microCi and the radiation dose to the thyroid gland was on the average of 0.5 Gy. The cohort was matched with the Swedish Cancer Register for the years 1958-1984. During this period, 3746 cancers occurred more than 5 years after the 131I examination, and the resulting standardized incidence ratio (SIR) was 1.01 (95% confidence interval [CI] = 0.98 to 1.04). SIR for thyroid cancer was 1.18 (95% CI = 0.88 to 1.56). The risks for both cancer of all sites and for thyroid cancer were highest 5 to 9 years after examination (SIR = 1.07 and 2.06, respectively) and did not differ from unity thereafter. With greater than or equal to 10 years of follow-up, risk was not statistically associated with the dose of 131I.     

Cancer risks in ulcerative colitis patients

Patients diagnosed with ulcerative colitis (UC) are known to be at an increased risk of colorectal and liver cancers and leukemia. UC is an autoimmune disease, which may present a wider spectrum of cancers. We wanted to examine the risk of cancer in a large population of UC patients in order to reach high statistical power. A UC research database was constructed by identifying UC patients from the Swedish Hospital Discharge Register and cancer patients from the Cancer Registry. Follow-up of 27,606 UC patients hospitalized for the first time during the years 1964-2004 identified 2,058 patients with cancer. Standardized incidence ratios were calculated for cancer in UC patients by comparing to subjects without hospitalization for UC. The novel tumor sites in UC patients included small intestinal (carcinoid), pancreatic, breast and prostate cancers, nonthyroid endocrine gland tumors, non-Hodgkin lymphoma and multiple myeloma. A total of 11 sites showed an increased risk, which remained at 6 sites when tumors diagnosed in the year of UC hospitalization were excluded; even chronic myeloid leukemia was in excess. Cancer risks depended on the age at first hospitalization for UC. The SIRs for colon, rectal, liver and pancreatic cancers declined by age at hospitalization for UC, while for endocrine tumors the older patients were at higher risk. Our large study identified novel subsequent cancers in UC patients. However, some of these, including small intestinal carcinoids, prostate cancers and nonthyroid endocrine tumors, may be in excess because of intensified medical surveillance of the patients.     

Cancer risks in Crohn disease patients

Background: Patients diagnosed with Crohn disease (CD) are knownto be at an increased risk of bowel cancers and lymphoma. CDis an autoimmune disease and we hypothesize that the patientsare predisposed to a wider spectrum of cancers. Patients and methods: A CD research database was constructedby identifying hospitalized CD patients from the Hospital DischargeRegister and cancer patients from the Swedish Cancer Registry.Follow-up of 21 788 CD patients first hospitalized during theyears 1964–2004 identified 1424 cancer cases. Standardizedincidence ratios (SIRs) were calculated by comparing cancersin CD patients with subjects without CD. Results: In addition to the known sites, many additional siteswere in excess in CD patients. These included liver, pancreatic,lung, prostate, testicular, kidney and skin (squamous cell)cancers; nonthyroid endocrine tumors and leukemia. The previouslyestablished sites showed the highest SIRs; however, SIRs >2.0were noted for the novel sites of the liver, testis and kidney.For testicular cancer, the SIR of seminoma was 2.74. Cancerrisks were influences by age at first hospitalization for CDbut whether the age effects were increasing or decreasing dependingon the cancer type. Conclusions: This large study identified many novel subsequentcancers in CD patients. Key words: age at onset, autoimmunity, cancer risk, inflammatory bowel disease, subsequent cancerReceived for publication February 22, 2008. Revision received July 29, 2008. Accepted for publication July 30, 2008.     

Cancer risks and cancer prevention in Sweden

Sweden has had cancer and population registers since 1958, indicating an increasing total age-adjusted cancer incidence. The incidence of liver, prostate and urinary tract cancer, as well as of melanoma and lymphoma, is increasing, whereas that of stomach cancer and Hodgkin's lymphoma is decreasing. National public recommendations by the nutrition and exercise committee of the National Board of Health and Welfare to reduce fat, salt, energy and sugar intake and to increase fiber intake and exercise have existed for 20 yr. The purpose was initially to prevent cardiovascular diseases, later also to prevent breast and prostatic cancer. Since the 1970s, Swedish women have been offered systematic gynecological health checks, resulting in a reduced incidence and mortality of cervix carcinoma. Local Swedish studies suggest that systematic mammography, which is now recommended on a national basis, can reduce breast cancer mortality by 30%. It is estimated that between 300 and 1100 cases of bronchopulmonary carcinoma are partly caused by a dwelling environment with over 400 Bq radon m-3. General rebuilding of the 40,000 houses concerned is at present being considered.     

Breast cancer risks in relatives of male breast cancer patients.

BACKGROUND: Previous studies have provided conflicting results concerning the familial effect of male breast cancer on breast cancer risks in female relatives. PURPOSE: We studied breast cancer risks in first-degree relatives of male patients and compared them with relatives of female patients. METHODS: Our study included 88 consecutively ascertained male patients and 320 of their first-degree relatives as well as 186 consecutively ascertained female patients and 633 of their first-degree relatives. Observed numbers of breast cancers in relatives were compared with the expected number derived from the Connecticut Tumor Registry. Multiple logistic regression analysis was also performed. RESULTS: Relatives of male patients exhibited a significant twofold increased risk when compared with expected rates and no difference in risk when compared with that of relatives of female patients. Prostate cancer in the family of a male patient resulted in a significant fourfold increased breast cancer risk compared with a risk of 1.4 in families with no history of prostate cancer. A family history of lung cancer, colon cancer, or melanoma had no effect on increasing risks of breast cancer. CONCLUSION: The familial effect of male breast cancer is the same as that of female breast cancer. IMPLICATIONS: Any estimates of breast cancer risk provided to individuals should also consider the occurrence of prostate cancer in the family, since prostate cancer appears capable of at least doubling the underlying twofold risk.     

Reproductive and gynecological complication risks among thyroid cancer survivors

Purpose

Thyroid cancer is the most rapidly increasing cancer in the USA, affects a young, mostly female population, and has high survival. The aim of this study was to determine if there is an increased risk of reproductive system adverse events or pregnancy complications among women diagnosed with thyroid cancer under the age of 50.

Methods

Up to five female cancer-free individuals were matched to each female thyroid cancer survivor diagnosed before the age of 50 based on birth year, birth state, and follow-up time, within the Utah Population Database. Medical records were used to identify disease diagnoses stratified over three time periods: 0–1, >?1–5, and >?5–10 years after cancer diagnosis. Cox proportional hazards models were used to estimate hazard ratios (HR) with adjustment on matching factors, race, BMI, and Charlson Comorbidity Index.

Results

There were 1832 thyroid cancer survivors and 7921 matched individuals. Thyroid cancer survivors had higher rates of having multiple health conditions associated with the gynecological system (15.4% vs. 9.4%) and pregnancy (14.3% vs 9.5%) >?1–5 years after cancer diagnosis. Increased risks persisted >?5–10 years after cancer diagnosis for menopausal disorders (HR?=?1.78, 99% CI?=?1.37, 2.33) and complications related to pregnancy (HR?=?2.13, 99% CI?=?1.14, 3.98). Stratified analyses showed these risks remained increased across different treatment types.

Conclusions

There were significant risk increases in reproductive system and pregnancy complications among female thyroid cancer survivors within this study.

Implications for Cancer Survivors

Although radiation has been linked to reproductive risks in previous studies, we found risks were increased in patients regardless of treatment.

     

Cancer risks after medical radiation.

Radiation-induced tumors cannot be distinguished from tumors in general by means other than a statistical excess. Epidemiological studies are the only means by which answers can be given as regards the carcinogenic effect of ionizing radiation. Age at exposure is perhaps the most important host factor influencing cancer risk and it is generally believed that cancer risk decreases with increasing age at exposure. For most cancers the temporal pattern follows the natural incidence, i.e. the cancers do not occur before ages normally associated with increased incidence. The induction period for solid tumors is at least 10 years while the corresponding figure for leukemia is 2 years. The breast, thyroid, lung and bone marrow seem to be the most radiosensitive tissues, while the risk of chronic lymphatic leukemia and possibly Hodgkin's disease and prostatic cancer does not seem to increase after exposure to ionizing radiation.     

Tumors after radiotherapy for thyroid cancer. A case-control study within a cohort of thyroid cancer patients.

A case-control study of Swedish thyroid cancer patients was conducted to evaluate the possible influence of 131I treatment and external radiotherapy on the risk of developing a subsequent cancer. Both cases and controls derived from a cohort of Swedish thyroid cancer patients treated with 131I (n = 834) or by other means (n = 1,121). Thirty-six breast, 13 stomach, 12 kidney, and 5 bladder cancers were found more than 2 years after 131I treatment/thyroid cancer diagnosis. Individual, absorbed dose in the organs was calculated by using ICRP tables, administered activity of 131I, and 24-h 131I uptake. In studying the effect of 131I and external radiotherapy no statistically significant dose-response relationships were found for cancers of the breast, stomach, bladder or kidney. When the absorbed dose from 131I was analyzed separately the risks remained essentially the same. The present follow-up time and the relatively low absorbed dose that the patients received from 131I and external radiotherapy necessitate studies with a longer follow-up time or a larger patient material before more firm conclusions can be made.     

Cellular radiosensitivity of patients with papillary thyroid cancer.

Cultured skin fibroblasts from patients with papillary (differentiated) thyroid carcinomas were compared to those from healthy subjects, ataxia telangiectasia (AT) homozygotes and AT heterozygotes for colony-forming ability after low dose-rate irradiation, and post-irradiation DNA synthesis as indicated by uptake of [3H]-thymidine. The cells from the cancer patients exhibited enhanced radiosensitivity (intermediate between normal and AT) and less than normal level of radioinduced inhibition of DNA synthesis.     

Glutathione S-transferase polymorphisms in thyroid cancer patients

Glutathione S-transferases (GST) are enzymes involved in the metabolism of many carcinogens and mutagens, also acting as important free-radical scavengers. The existence of different genetic polymorphisms in human populations has proven to be a susceptibility factor for different tumours. Nevertheless, as far as we know, for thyroid cancer no study has been conducted until now linking its incidence to genetic susceptibility biomarkers. The present investigation has been conducted to detect the possible association between polymorphism at the GSTM1, GSTT1 and GSTP1 genes and thyroid cancer incidence. Thus, 134 thyroid cancer patients and 116 controls, all from the urban district of Barcelona (Spain), have been included in this study. The results indicate that, according to the calculated odds ratio, the frequencies of the different genotypes found in the group of cancer patients do not significantly differ from those values obtained in the controls. This is true for the overall data as well as for the tumour characterization as follicular and papillar types. In addition, none of the possible combinations of mutant genotypes were shown to be risk factors. Finally, when the sex of the patients, the age of tumour onset, and life-style habits were also taken into account, no influence was observed related to the different genotypes. In conclusion, the results obtained in this study clearly suggest that those susceptibility factors related to the different GST polymorphic enzymes are not a predisposing factor in thyroid cancer disease.     

Continuing reassessment of the risks of erythropoiesis-stimulating agents in patients with cancer.

PURPOSE: Erythropoiesis-stimulating agents (ESA) are approved for the treatment of anemia in patients with nonmyeloid malignancies whose anemia is due to the effect of concomitantly administered chemotherapy. Since the 1993 approval of epoetin alfa in patients with cancer, the risk of thrombovascular events, decreased survival, and poorer tumor control have been increasingly recognized. The risks of ESAs in patients with cancer and the design of trials to assess these risks have been the topic of discussion at two Oncologic Drugs Advisory Committees in 2004 and 2007. EXPERIMENTAL DESIGN: Evaluation of randomized clinical trials comparing use of ESAs to transfusion support alone in patients with active cancer. RESULTS: Six studies (Breast Cancer Erythropoeitin Survival Trial, Evaluation of NeoRecormon on outcome in Head And Neck Cancer in Europe, Danish Head and Neck Cancer, Lymphoid Malignancy, CAN-20, and Anemia of Cancer) investigating ESAs in oncology patients showed decreased survival, decreased duration of locoregional tumor control, and/or increased risk of thrombovascular events. In these six studies, ESA dosing was targeted to achieve and maintain hemoglobin values in excess of current recommendations, and in three of the six studies, ESAs were administered to patients not receiving chemotherapy. CONCLUSIONS: ESAs increase the risk of thrombovascular events and result in decreased survival and poorer tumor control when administered to achieve hemoglobin levels of > or =12 g/dL in patients with nonmyeloid malignancies. No completed or ongoing randomized, controlled trial has addressed safety issues of ESAs in patients with chemotherapy-associated anemia using currently approved dosing regimens in an epidermal tumor type. Additional studies are needed to better characterize these risks.     

Second primary malignancies in thyroid cancer patients

The late health effects associated with radioiodine ((131)I) given as treatment for thyroid cancer are difficult to assess since the number of thyroid cancer patients treated at each centre is limited. The risk of second primary malignancies (SPMs) was evaluated in a European cohort of thyroid cancer patients. A common database was obtained by pooling the 2-year survivors of the three major Swedish, Italian, and French cohorts of papillary and follicular thyroid cancer patients. A time-dependent analysis using external comparison was performed. The study concerned 6841 thyroid cancer patients, diagnosed during the period 1934-1995, at a mean age of 44 years. In all, 17% were treated with external radiotherapy and 62% received (131)I. In total, 576 patients were diagnosed with a SPM. Compared to the general population of each of the three countries, an overall significantly increased risk of SPM of 27% (95% CI: 15-40) was seen in the European cohort. An increased risk of both solid tumours and leukaemias was found with increasing cumulative activity of (131)I administered, with an excess absolute risk of 14.4 solid cancers and of 0.8 leukaemias per GBq of (131)I and 10(5) person-years of follow-up. A relationship was found between (131)I administration and occurrence of bone and soft tissue, colorectal, and salivary gland cancers. These results strongly highlight the necessity to delineate the indications of (131)I treatment in thyroid cancer patients in order to restrict its use to patients in whom clinical benefits are expected.     

Cancer screening in patients with cancer

Interest in multiple primary malignant neoplasms is long-standingsince the Warren–Gates report (1) in 1932. We have theimpression that multiple cancer cases have recently been increasingin number. Multiple primary neoplasms in the same individualare experienced more frequently as advances in cancer treatmentprolong life. Improved survival rates for patients with neoplasticdisease, largely due to early diagnosis, allow more patientsto survive long enough to develop subsequent primary tumors. The development of more sophisticated invasive and non-invasivediagnostic tools has made it possible to detect cancer at anearly stage. Furthermore, it has contributed to the detectionof synchronous occult tumors which were formerly overlooked.Cases of multiple primary cancers raise questions about underlyingenvironmental factors     

Distant metastases in papillary thyroid cancer. A review of 91 patients

Of 731 patients with papillary thyroid cancer, 91 had metastases outside regional lymph nodes. The most common site was intrathoracic, occurring in 73 of the 91 patients. Miliary, micronodular pulmonary metastases, with iodine 131 (I-131) uptake and "curable" by I-131 treatment were encountered in seven patients. It has not been established whether this was a transient stage in additional patients. In 38 patients rounded, macronodular pulmonary metastases were found. Another 21 patients had unilateral pulmonary infiltration and mediastinal enlargement. Pulmonary infiltrations may be hematogenic, or may possibly occur via regional, mediastinal lymph nodes. Mortality within 1 year of the diagnosis of distant metastases exceeded 50%. Occurrence of distant metastases showed a slight but highly significant association with male sex, advanced age, and advanced local tumor stage. Better prognostic determinants are, however, required if adequate of the individual patient with papillary thyroid cancer is to be achieved.     

Cancer risks in women with 2 breast or ovarian cancers: clues to genetic cancer susceptibility.

Women diagnosed with 2 cancers of the breast and/or ovary are at higher risk of developing subsequent cancers. Using registrations from the Thames Cancer Registry, we quantified the risks at different cancer sites. Increased risks were found for cancers that are part of the BRCA1 and BRCA2 tumour spectrum: oropharyngeal cancer, malignant melanoma of the skin (BRCA2) and colon cancer (BRCA1). We also found significantly increased risks of myeloid leukaemia (probably due to radiotherapy) and of cancer of the corpus uteri (which may be due to hormonal factors).