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Biomedical subjects

J T Flannery

Publications and source records attributed to J T Flannery.

At least 37 records · Page 2Linked to original sources

Cancer in the contralateral breast after radiotherapy for breast cancer.

BACKGROUND: Patients with breast cancer have a threefold increase in the risk that a second breast cancer will develop. Radiation treatment for the initial cancer can result in moderately high doses to the contralateral breast, possibly contributing to this heightened risk. METHODS: We conducted a case-control study in a cohort of 41,109 women diagnosed with breast cancer between 1935 and 1982 in Connecticut. We reviewed the medical records of 655 women in whom a second breast cancer developed five or more years after the initial tumor and compared their radiation exposure with that of 1189 matched controls from the cohort who did not have a second cancer. The dose of radiation to the contralateral breast was estimated from the original radiotherapy records. Among the exposed women, the average radiation dose to the contralateral breast was 2.82 Gy (maximum, 7.10). RESULTS: Overall, 23 percent of the women who had a second breast cancer and 20 percent of the controls had received radiotherapy (relative risk of a second breast cancer associated with radiotherapy, 1.19). Among women who survived for at least 10 years, radiation treatment was associated with a small but marginally significant elevation in the risk of a second breast cancer (relative risk, 1.33); the risk increased significantly with the dose of radiation. An increase in risk in association with radiotherapy was evident only among women who were under 45 years of age when they were treated (relative risk, 1.59) and not among older women (relative risk, 1.01). CONCLUSIONS: Radiotherapy for breast cancer contributes little to the already high risk of a second cancer in the opposite breast. Fewer than 3 percent of all second breast cancers in this study could be attributed to previous radiation treatment; the risk, however, was significantly increased among women who underwent irradiation at a relatively young age (less than 45 years). Radiation exposure after the age of 45 entails little, if any, risk of radiation-induced breast cancer.

Adult↗

Association between childhood rhabdomyosarcoma and maternal history of stillbirths.

A case/control study of childhood rhabdomyosarcoma (RMS) was conducted utilizing information from birth records. Cases among Connecticut residents age 19 and younger diagnosed between 1960 and 1988 were identified from the Connecticut Tumor Registry files. Connecticut birth certificates were located for 103 of the 130 cases identified. A random sample of control birth certificates was frequency-matched to the cases by year of birth, sex, and ethnic origin, with a control:case ratio of 2:1. Information abstracted from birth certificates included birth weight, length of pregnancy, plurality, birth order, mother's prior stillbirths, mother's age, father's age, and father's occupation. Data were analyzed by conditional logistic regression. The major finding was an association between RMS and the mother having had one prior stillbirth or more (odds ratio = 3.7; 95% confidence interval = 1.5 to 8.9). Particularly noteworthy was the observation that 6 mothers of cases, but no mothers of controls, had had 2 or more prior stillbirths. The trend for increasing risk of RMS with increasing number of mother's prior stillbirths was highly significant (p = 0.0004). This association suggests that RMS and a class of stillbirths share a common etiologic factor. This factor may be genetic or may involve in utero exposure to an exogenous or endogenous agent.

Birth Weight↗

Stomach cancer patterns in European immigrants to Connecticut, United States.

Age-adjusted annual incidence rates of stomach cancer (ICD-9 code #151) were examined for the period 1973-88 among Connecticut residents who were born in the United States or who emigrated from one of five European nations (Italy, Poland, the United Kingdom, Germany, Portugal). Risk of stomach cancer among each of the five immigrant groups was elevated significantly above that of US-born residents. The magnitude of difference ranged from a 1.62-fold excess among persons born in Italy to a 4.27-fold increase in risk among persons born in Portugal. Cancer risk to foreign-born residents was less than that observed in their native countries, with decreases of 25-64 percent found here. Several differences in patient and disease characteristics were observed according to country of birth. Compared with US-born residents, there was a lesser predominance of males among patients born in Italy, Poland, and the UK. Among all foreign-born groups, the gastric cardia was involved less frequently, and the pyloric region more frequently, than in US-born patients. Adenocarcinomas were significantly less common among Polish-born cases. The findings suggest different etiologies in foreign and US-born patients.

Adolescent↗

Time trends in malignant melanoma of the upper limb in Connecticut.

Time trends in the incidence of malignant melanoma of the anatomic subsites of the upper limb in Connecticut from 1935 to 1984 were examined. Among males, the incidence of melanoma of the hand was stable, in sharp contrast to the 15-fold to 16-fold increase in the upper arm and forearm. Among females, the 3-fold increase in melanoma of the hand was substantially less than the 12-fold to 14-fold increase in the upper arm and forearm. However, melanoma of the dorsal surface of the hand in females increased sevenfold. These results are in partial agreement with the hypothesis that the hand would be relatively resistant to increased melanoma incidence because it has continually been a sun-exposed site over the decades. The results contradict the hypothesis that the rise in incidence would be greater in the upper arm (a usually unexposed site that has received increasing exposure due to changes in recreation and dress habits) than in the forearm (a site of intermediate exposure).

Arm↗

Incidence of childhood cancer in twins.

The incidence of childhood cancer in twins was evaluated by linking a roster of 30,925 twins born in Connecticut (United States) between 1930 and 1969 with the Connecticut Tumor Registry. Cancer, exclusive of nonmelanoma skin cancer, was identified in 19 females and 12 males under 15 years of age. The incidence rate among twins was 7.9 cancers per 100,000 person-years (PY) overall, and 9.7 and 6.1 per 100,000 PYs for females and males, respectively. Four of 13 leukemias occurred in two female twin pairs, representing concordance rates of 18 percent overall and 29 percent for like-sex pairs, which are somewhat higher than values reported previously. The number of cancers expected was computed on the assumption that twins experienced the same sex-, age-, and calendar time-specific cancer rates as recorded for all Connecticut-born children. Because active follow-up of individuals was not conducted, an adjustment to person-years of observation was made to account for childhood mortality, including the high perinatal mortality characteristic of twins. Childhood cancer was 30 percent less frequent than expected (standardized incidence ratio [SIR] = 0.7; 95 percent confidence interval [CI] = 0.5-0.9), a deficit that is marginally greater than those found in previous studies. Both leukemia (SIR = 0.8; CI = 0.4-1.4), and all other cancers combined (SIR = 0.6; CI = 0.3-0.9) occurred less often than expected. The deficit was greater among males (SIR = 0.5; CI = 0.2-0.8) than among females (SIR = 0.9; CI = 0.5-1.4) and was especially pronounced among males younger than five years (SIR = 0.2; CI = 0.0-0.7). The data support the view that twins, particularly male twins, have a lower risk of childhood cancer than single-born children. Any added risk for twins associated with their greater frequency of exposure to prenatal X-rays appears to have been insufficient to offset an 'effect' of twinning per se. Possible explanations for this finding include (i) the low birthweight distribution of twins, or (ii) selective early mortality of twin fetuses or neonates who would otherwise have developed a clinical cancer.

Adolescent↗

Cervical cancer rates by population size of towns: implications for cancer control programs.

Incidence rates and standardized incidence ratios (SIRs) for invasive and in situ cervical cancers diagnosed in 1982-87 were analyzed according to total population size of 148 towns, using data from the population-based Connecticut Tumor Registry. Previous studies have not considered socioeconomic or sociodemographic variables in analyzing cervical cancer rates in urban-rural or population density groups. In multiple regression analyses, increases in SIRs for invasive and in situ cancer from medium-sized to large towns were explained by differences in poverty prevalence or other socio-demographic variables. Nevertheless, cancer screening programs (aimed at preventing invasive cancer through early detection) could be targeted to some extent on the basis of town size category, because larger towns include large numbers of poorer and minority women with higher rates of invasive cervical cancer. SIRs for in situ cancer were significantly elevated in the largest towns (100,000 + total population), and primary prevention programs could target these larger towns with a higher prevalence of poverty.

Adolescent↗

Increasing incidence of cecal and sigmoid carcinoma. Data from the Connecticut Tumor Registry.

We have studied both the distribution and incidence of colorectal cancer using The Connecticut Tumor Registry, the oldest tumor registry in the United States. During the time period 1973 to 1985, left-sided colon cancers accounted for 63% of the cancers, right-sided cancers 33%, and cancers with unspecified sites 4%. Indeed, this pattern of distribution has remained constant for 25 years. For the period 1935 to 1985, we calculated the sex-specific, age-adjusted (normalized to the 1970 U.S. Census) incidence. Age-adjusted incidence of rectal cancer has remained stable for 50 years: for men, 22.8 cases/100,000/year, and for women, 13.9 cases/100,000/year. During these 50 years, the age-adjusted incidence of cecal carcinoma for men has increased from 3.6 to 16.7 cases/100,000/year, while for women, it has increased from 4.9 to 14.2 cases/100,000/year. Sigmoid carcinoma for men has increased from 8.8 to 18.7 cases/100,000/year, and for women, it has increased from 7.7 to 12.8 cases/100,000/year. The incidence of colon cancer at each site has been and continues to be increasing at a constant rate. Age-adjusted incidence for all colorectal cancers has increased from 35.2 to 70.2 cases/100,000/year for men and from 32.1 to 49.2 cases/100,000/year for women. Thus, distribution of colorectal cancers by site in Connecticut has remained stable for 25 years. More importantly, however, the age-adjusted incidence of colon cancer has continued to increase for 50 years, whereas that of rectal cancer has remained relatively stable.

Cecal Neoplasms↗

Leukemia following chemotherapy for breast cancer.

Leukemia following chemotherapy for breast cancer was studied among patients diagnosed during 1973-1985 within the population-based tumor registries in the Surveillance, Epidemiology, and End Results Program. Among 13,734 women given initial chemotherapy, 24 developed acute nonlymphocytic leukemia (ANLL) compared to 2.1 expected based on general population rates (observed/expected = 11.5; 95% confidence interval = 7.4-17.1). Overall, 58 excess ANLL occurred per 100,000 women-years at risk for patients treated with chemotherapy. The cumulative incidence was 0.7% at 10 years. Risk remained high over all periods of observation up to 9 years after treatment. Among 7974 women treated only with surgery during 1973 and 1974, a period before the widespread use of adjuvant chemotherapy for breast cancer, ANLL was not significantly increased (observed = 7, expected = 5.1). A case-control study was then conducted in Connecticut to evaluate in more detail the risk associated with adjuvant chemotherapy in the general population. Among 20 cases (17 incident leukemias and 3 deaths due to preleukemia) and 60 matched controls, alkylating agents were linked to an 11.9-fold risk of ANLL and preleukemia (95% confidence interval = 2.6-55). Chemotherapy regimens including melphalan were related to a higher risk of leukemic conditions than those including cyclophosphamide. These data suggest that women in the general population treated with adjuvant chemotherapy for breast cancer are at an increased risk of leukemia, that the risk remains high among long-term survivors, and that risk differs by type of alkylating agent administered.

Age Factors↗

Pinealomas and germinomas in children.

A series of 34 pinealomas and intracranial germinomas in childhood (age less than 20), from two tumor registries, is analyzed. Male to female ratio was 2:1. Median age was 12 years. Visual complaints and endocrine disturbances were the most common presenting symptoms. Papilledema, visual field deficits, and oculomotor abnormalities were the principal findings at diagnosis. Cumulative probability of survival (CPS) of the entire series at one year was 0.65, at two years 0.54, and at five years 0.54. Best survival was with treatment by operation and radiation: CPS at one year was 0.82, at two years 0.82, and at five years still 0.82. Survival was similar with pineal region tumors and with suprasellar tumors. Most long-term survivors, particularly with suprasellar germinomas, had permanent hormonal deficits requiring replacement therapy.

Adolescent↗

Leukemia risk following radiotherapy for breast cancer.

To evaluate further the relationship between high-dose radiotherapy and leukemia incidence, a nested case-control study was conducted in a cohort of 22,753 women who were 18-month survivors of invasive breast cancer diagnosed from 1935 to 1972. Women treated for breast cancer after 1973 were excluded to minimize the possible confounding influence of treatment with chemotherapeutic agents. The cases had histologically confirmed leukemia reported to the Connecticut Tumor Registry (CTR) between 1935 and 1984. A total of 48 cases of leukemia following breast cancer were included in the study. Two controls were individually matched to each leukemia case on the basis of age, calendar year when diagnosed with breast cancer, and survival time. Leukemia diagnoses were verified by one hematologist. Radiation dose to active bone marrow was estimated by medical physicists on the basis of the original radiotherapy records of study subjects. Local radiation doses to each of the 16 bone marrow components for each patient were reconstructed; the dose averaged over the entire body was 530 rad (5.3 Gy). Based on this dosage and assuming a linear relationship between dose and affect, a relative risk (RR) in excess of 10 would have been expected. However, there was little evidence that radiotherapy increased the overall risk of leukemia (RR = 1.16; 90% confidence interval [CI], 0.6 to 2.1). The risk of chronic lymphocytic leukemia, one of the few malignancies without evidence for an association with ionizing radiation, was not significantly increased (RR = 1.8; n = 10); nor was the risk for all other forms of leukemia (RR = 1.0; n = 38). There was no indication that risk varied over categories of radiation dose. These data exclude an association between leukemia and radiotherapy for breast cancer of 2.2-fold with 90% confidence, and provide further evidence that cell death predominates over cell transformation when high radiation doses are delivered to limited volumes of tissue.

Aged↗

Late-stage diagnosis of breast cancer in women of lower socioeconomic status: public health implications.

To assess the success of breast cancer control activities in Connecticut, we examined data from the Connecticut Tumor Registry, determining differences in breast cancer stage at time of diagnosis over time and in selected subgroups. From 1982 to 1985, the percentage of women with cancer confined to the breast increased from 54.0 percent to 61.3 percent. During 1984 and 1985, lower socioeconomic status (SES) women with breast cancer were less likely than higher SES women to be diagnosed with early-stage disease (56.9 percent vs 62.7 percent). SES was estimated by census tract of residence. In the same years, the overall incidence of breast cancer was greater in higher SES women. Projections based on these incidence data found that lower SES women, as compared to higher SES women, had a higher rate of expected breast cancer deaths (24.6 vs 19.7 per 100,000), and a greater percentage of those deaths considered preventable by early detection (22 percent vs 11 percent). The rate of preventable deaths in lower SES women was 2.5 times as great as that for higher SES women (5.3 vs 2.1 per 100,000). Tumor registries can serve as useful surveillance systems to aid cancer control programs. Breast cancer early-detection programs should give special attention to lower SES women.

Black or African American↗

Clear cell adenocarcinoma of the vagina and cervix: incidence, undetected disease, and diethylstilbestrol.

We conducted an incidence study to determine the occurrence rates of clear cell adenocarcinoma (CCAC) of the vagina and cervix in young women (born in 1940 and thereafter), and a case-series analysis, focusing on the maternal history of pregnancy and delivery and in-utero exposure to diethylstilbestrol (DES). Overall, 10 cases of CCAC had been listed in the files of the Connecticut State Tumor Registry prior to the study, and each of the 10 cases were confirmed as valid. In addition, another 10 cases, all previously undetected, were found after the tissue slides of young women listed as having other cancers of the vagina and cervix were reviewed by expert pathologists, suggesting that prior estimates of the incidence rate for CCAC must be misleading unless special efforts are taken to identify undetected cases. The incidence rates of vaginal CCAC (11 cases total) were highest in 1975-1979, and decreased slightly during 1980-1982. In the cervix (nine cases total), the rate increased consistently since 1970. History of in-utero exposure to diethylstilbestrol was obtained for five of eight vaginal cases and four of eight cervical cases of CCAC. In all nine cases, exposure to diethylstilbestrol was associated with a history of bleeding during the pregnancy or prior miscarriage. We conclude that the finding of stable (or rising) incidence rates for CCAC occurring nearly 30 years after the marked decrease in diethylstilbestrol sales emphasizes the need for continued clinical and epidemiologic studies of the etiology and clinical course of CCAC.

Abortion, Spontaneous↗

Adult occurrence of medulloblastoma.

We analyze a series of 44 medulloblastomas in patients aged 20 and older, listed in the Connecticut Tumor Registry. Average age was 34.1 years. Incidence was 0.058 per 100,000 per year. Headache and ataxia were the most frequent presenting complaints. Findings at diagnosis most often were papilloedema, cranial nerve palsies, and cerebellar dysfunction. Treatments included operation (15%), radiation (7%), and operation plus radiation (60%). Probability of survival at one year was 0.62; at five years, 0.26. Survival with operation and radiation was superior to survival with other courses of treatment. Extracranial metastases to the spinal cord, the bones, and the pleura occurred in 27% of cases. For the first two years from diagnosis, survival in this series was significantly better than survival in the contemporary series of children with medulloblastoma. At five years and ten years, survival in adults and children was comparable.

Adult↗

A population-based case-control study of thyroid cancer.

A population-based case-control interview study of thyroid cancer (159 cases and 285 controls) was conducted in Connecticut. Prior radiotherapy to the head or neck was reported by 12% of the cases and 4% of the controls [odds ratio (OR) = 2.8; 95% confidence interval = 1.2-6.9]. Risk was inversely related to age at irradiation and was highest among children exposed under age 10. Few persons born after 1945 received prior radiotherapy, consistent with the declining use of radiation to treat benign conditions in the 1950's. Among females the radiogenic risk appeared to be potentiated by the number of subsequent live-births. Other significant risk factors included a history of benign thyroid nodules (OR = 33) or goiter (OR = 5.6). Miscarriage and multiparity increased risk but only among women who developed thyroid cancer before age 35 years. Consumption of shellfish (a rich source of iodine) seemed to increase the risk of follicular thyroid cancer, whereas consumption of goitrogen-containing vegetables appeared to reduce risk of total thyroid cancer, possibly because of their cruciferous nature. A significantly low risk was observed among persons of English descent, whereas Italian ancestry appeared to increase risk. No significant associations were found with a number of suspected risk factors: diagnostic x-rays, radioactive isotope scans, occupational radiation exposure, tonsillectomy, Jewish ethnicity, alcohol intake, cigarette smoking, oral contraceptives, lactation suppressants, menopausal estrogens, most other common medications, and water source. New associations were suggested for obesity among females (OR = 1.5), surgically treated benign breast disease (OR = 1.6), use of spironolactone (OR = 4.3) or vitamin D supplements (OR = 1.8), and a family history of thyroid cancer (OR = 5.2). About 9% of the incident thyroid cancers could be attributed to prior head and neck irradiation, 4% to goiter, and 17% to thyroid nodular disease, leaving the etiology of most thyroid cancers yet to be explained.

Adult↗

Nasopharyngeal cancer, sinonasal cancer, and occupations related to formaldehyde: a case-control study.

Formaldehyde vapor induces cancer of the nasal passages in laboratory animals. In this case-control epidemiologic study, occupational information was obtained for 198 persons with sinonasal cancer (SNC), for 173 with nasopharyngeal cancer (NPC) identified as incident cases by the Connecticut Tumor Registry over 41 years among Connecticut males dying of any cause, and for 605 controls sampled from Connecticut death certificates. City directories and death certificates provided information on job, industry, employer, and year of employment for exposure classification. Without knowledge as to case-control status, an industrial hygienist particularly experienced in epidemiologic studies of formaldehyde classified each study subject with respect to probability and degree of formaldehyde exposure. For those with probable exposure to the high level 20+ years prior to death the odds ratio for NPC was 2.3 [95% confidence limits (CL): 0.9, 6.0], and for those with this same risk factor among men dying at age 68+ (the median study age at death or older) the odds ratio was 4.0 [95% CL: 1.3, 12.0--with two-sided P = .015, unadjusted for multiple significance tests, and with two-sided P = .129 in testing for interaction between this risk factor (never any exposure vs. probable exposure to high level 20+ years prior to death) and age (age less than 68 yr vs. age 68+ yr)]. Odds ratios were close to unity for 9 of 13 industries. Formaldehyde-related occupations in printing appeared to be associated with any type of nasal cancer (either SNC or NPC).

Formaldehyde↗

Risk of second malignancy after cancers of the renal parenchyma, renal pelvis, and ureter.

Risk of second primary malignancy was assessed in a population-based survey of persons who developed cancers of the renal parenchyma, renal pelvis, or ureter in Connecticut during the period 1935-1982. Among 4176 patients with a first primary tumor of the renal parenchyma, a second cancer was reported in 219 (5%), yielding a small but significantly elevated relative risk (RR) of 1.2, which reflects excesses for cancers of the bladder, kidney, and lymphatic-hematopoietic system. Among 939 patients with a first primary tumor of the renal pelvis or ureter, a second cancer was reported in 155 (17%), associated with a significantly elevated RR of 2.7. This resulted mainly from a 21-fold increase in risk for bladder cancer, although significant excesses were also found for lung and prostate cancers, and metachronous cancers of the renal pelvis and ureter. These associations seem to reflect the multicentric behavior of tumors arising in the urinary tract, the role of cigarette smoking, and host factors yet to be defined, and some degree of heightened medical surveillance and detection of tumors, especially in the same organ system.

Aged↗

Testicular cancer in the United States: trends in incidence and mortality.

The patterns of incidence and mortality of testicular cancer in the United States indicate substantial differences by age, race, time period, and geographical region. An epidemic increase over time in the risk of testicular cancer is noted for young men aged 15-44, with the most recent birth cohorts showing the greatest rate of increase. Indeed, some of the evidence suggests the possibility of two separate increases, one apparent from at least the late 1930's through the late 1950's and the second appearing in the late 1970's. The incidence data for blacks also show a young adult peak, even though the rates for whites are four to five times higher than for blacks at all ages except early childhood. Mortality rates for older men consistently declined over the 30-year period, while rates for younger men showed a dramatic drop only for the most recent time period. Aetiological factors yet to be determined may be responsible for the increasing incidence of testicular cancer in young adults. Survival factors appear to explain the age-specific differences between the incidence and mortality curves over time.

Adolescent↗

Bladder tumor incidence among workers exposed to benzidine: a thirty-year follow-up.

Linkage with records of the Connecticut Tumor Registry was used to determine cancer incidence in a cohort of workers (n = 984) at a benzidine manufacturing facility. Compared to the findings for the Connecticut population, there was a statistically significant excess of bladder tumor among male cohort members [standardized incidence ratio (SIR) = 343; 95% confidence limits (CL) = 148, 676; n = 830], which was confined to those with the highest estimated level of benzidine exposure (SIR = 1,303; CL = 479, 2,839; n = 105). No significantly elevated risks were found for cancers at other anatomic sites in men or at any anatomic sites in women; nor was there any pattern of increasing risk with increasing benzidine exposure for sites other than bladder. In addition, the elevated bladder cancer risk was greater for men first employed during the earliest years of the plant, namely, 1945-49 (SIR = 976; CL = 262, 2,498) as compared to those first employed in 1950-54 (SIR = 213; CL = 3, 1,184) after equalization of duration of follow-up. These results suggest that the major preventive measures instituted around 1950 may have reduced bladder cancer risk in this plant.

Adult↗