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Biomedical subjects

L Teppo

Publications and source records attributed to L Teppo.

At least 55 records · Page 3Linked to original sources

Serum p53 accumulation and altered antibody responses to Epstein-Barr virus proteins precede diagnosis of haemopoietic malignancies of lymphoid origin.

We analysed antibodies to Epstein-Barr virus nuclear antigens (EBNAs 1, 2, 5 and 6) and the presence of serum p53 in 100 individuals, 37 of whom has developed a haemopoietic malignancy during a 12-year follow-up of 39,000 Finnish adults. Serum p53 was detectable in six of the 63 (10%) matched controls and in 13/31 (42%) patients who developed a malignancy of lymphoid origin approximately 7 years after serum withdrawal. Six patients who developed a malignancy of myeloid origin were negative for p53. The presence of p53 alone was associated with a highly significant increased risk of lymphoid malignancies (relative risk (RR)p53 = 6.7, 95% confidence limits (CL) 1.9, 24) whereas high levels of antibody to EBNA2 seemed to be inversely related to the risk (RREBNA2 = 0.1, CL 0.0, 1.1). Among lymphoid malignancies, a combination of serum p53 and high EBNA1 antibody levels gave a greater than expected risk (RRp53 and EBNA1 = 14, CL 1.4, 130; RRexpected = 4.4), whereas interaction with high levels of EBNA5 antibody gave an expected risk (RRp53 and EBNA5 = 19, CL 1.7, 220; RRexpected = 17). Thus detectable levels of p53 appear early in the development of lymphoid malignancies, and high EBNA1 antibody levels, and accumulated p53 may both be synergistic risk indicators for lymphoid malignancies, whereas high EBNA5 antibody levels and accumulation of p53 seem to raise the RR independently of each other.

Adult↗

Risk of subsequent malignant neoplasms among 470,000 cancer patients in Finland, 1953-1991.

Because of increasing numbers of incident cancers and improving survival rates, more and more cancer patients are at risk of subsequent primary malignant neoplasms. The potential carcinogenicity of cancer therapies raises further concern regarding this unwanted long-term side effect. The objective of this cancer-registry-based study was to assess the trends in the risk of subsequent primary malignancies among cancer patients on a nationwide public-health level. The 470,000 cancer patients registered between 1953 and 1991 in Finland were followed up for subsequent primary neoplasms, and 19,800 subsequent malignant neoplasms were observed, yielding an overall standardized incidence ratio (SIR) of 1.00 for men and 1.25 for women. Substantial variation was observed in the SIR by the site of subsequent malignancy. The adjusted relative risk derived from multiple regression analyses showed only a slight increase by follow-up interval. Overall, the excess relative risk of subsequent malignancies was low, since the majority of cancer patients are old and at low relative risk. Patients under the age of 50 years, however, were at 70% increased risk, and the overall relative risk increased by 50% from the 1950s to the 1980s. Subsequent neoplasms among cancer patients do not pose a major public-health problem, but the possibility of subsequent cancers must be borne in mind in decisions concerning therapy and in clinical follow-up.

Adolescent↗

Risk of second cancers among lung cancer patients.

The risk of a second cancer among lung cancer patients was investigated using Finnish Cancer Registry data from 1953 to 1989. Among the 36,528 patients with a primary cancer of the lung, 504 new cancers were diagnosed six months or more after the diagnosis of lung cancer, yielding a standardized incidence ratio significantly lower than expected (SIR = 0.81). A significant excess of cancers of the larynx (SIR = 2.10) and urinary bladder (SIR = 1.35) was observed Among lung cancer patients below 60 years of age, the risks of oesophageal cancer (SIR = 2.47) and kidney cancer (SIR = 2.48) were also significantly elevated. The risk of a second cancer among lung cancer patients increased with the length of follow-up, and there was some indication of an excess risk of oesophageal cancer and leukaemia among lung cancer patients subject to radiotherapy.

Age Factors↗

Serum concentrations of prostate specific antigen and its complex with alpha 1-antichymotrypsin before diagnosis of prostate cancer.

Prostate cancer can be detected at an early, potentially curable stage by screening based on digital rectal examination and serum prostate specific antigen (PSA). The value of screening appears doubtful, based on high 10-year survival rates in selected cases of early prostate cancer, but this follow-up time may be insufficient. By linking the information on 21172 men who took part in a screening examination in Finland, 1968-73, with data from the Finnish Cancer Registry, 44 cases of prostate cancer diagnosed up to 1980 were identified. Serum samples from cancer cases and from 74 controls matched for age and time of sampling were assayed for PSA and its complex with alpha 1-antichymotrypsin (PSA-ACT). With a cut-off for PSA of 2.5 micrograms/L giving 92% specificity, 95% of the cancers developing within the first 5 years, and 52% developing in 6-10 years tested positive. As a potential screening test with a 5-year interval for men under 65, the sensitivity would be 92% and specificity 97%. The ratio of PSA-ACT to total PSA was lower in controls than in patients with cancer. Using this ratio, we could eliminate half of the false-positive results in the range 2.5-25 micrograms/L without loss of sensitivity. Cancer was typically diagnosed 5-10 years after PSA exceeded 2.5 micrograms/L, and the median survival after diagnosis was 3.6 years. 10-year survival after drawing the sample was 71% in cancer cases with a PSA concentration less than 4 micrograms/L and 48% in those with higher concentrations. The corresponding figures at 15 years were 53% and 27%, and at 20 years 43% and 18%, respectively. These results suggest it is advisable to confine screening for prostate cancer to men with a life expectancy of clearly more than 10 years--ie, younger men, who have the greatest chance to benefit from early detection.

Age Distribution↗

Testicular cancer in nine northern European countries.

The incidence of testicular cancer was examined in the Nordic and Baltic countries, Poland and Germany by collaboration among 10 cancer registries. Population-based registers were used to analyze a total of 34,309 cases, diagnosed from the start of registration (varying from 1943 in Denmark to 1980 in Latvia and Lithuania) through 1989. An approximately 10-fold geographical variation was found in 1980, with the highest age-standardized incidence rate (7.8 per 10(5); world standard population) in Denmark and the lowest (0.9) in Lithuania. During the entire period of registration, incidence increased rapidly in all countries, by 2.3 to 3.4 per cent annually in the Nordic countries and by about 5 per cent in Poland and Germany; there was some evidence of a slower increase in Denmark and Poland after 1975. The rising trend was more pronounced for ages below 30. The age-specific incidence peaked in all countries at ages 25 to 34, but the geographical variation was considerable. Our data indicate that environmental influences on testicular cancer are strong. Exposure to causal factors mostly takes place early in life, shows substantial geographical variation, and increases over time, so that the age-standardized incidence doubles every 15 to 25 years. New aetiological hypotheses are needed to accommodate these salient features of the descriptive epidemiology, since risk factors considered so far cannot explain the observed pattern.

Adolescent↗

Subsequent primary cancers following bladder cancer.

The incidence of a subsequent primary cancer was investigated among 10,014 patients with cancer of the urinary bladder diagnosed in 1953-1989 in Finland. During the follow-up period of 1953-1989, 652 new metachronous cancers were diagnosed. The number equals the expected number based on the national incidence figures. There were 195 second cancers of the lung. The standardised incidence ratio (SIR) for lung cancer was 1.3 among males [95% confidence interval (CI) 1.1-1.4] and 2.6 among females (95% CI 1.4-4.5). An increased SIR for larynx cancer in males (SIR = 1.7, 95% CI 0.91-2.8) and for kidney cancer in females (SIR = 3.6, 95% CI 1.8-6.2) was observed. The risk of a second cancer was greater among patients less than 60 years of age at the time of first diagnosis than among older patients. No consistent differences were observed in the risk of new cancer between bladder cancer patients treated with or without radiotherapy.

Adult↗

Bladder cancer and the risk of smoking-related cancers during followup.

The risk of smoking-related secondary cancers developing in bladder cancer patients was studied. The study population consisted of 10,014 bladder cancer patients reported to the Finnish Cancer Registry between 1953 and 1989. The risk of contracting a new primary cancer was estimated as a standardized incidence ratio, defined as the ratio of the observed and expected numbers of cases. Of 660 secondary cancers (6.6%) observed (standardized incidence ratio 0.96) 44% were considered to be smoking-related. Lung cancer was the most common secondary cancer (30% overall), and it occurred significantly more often than expected (standardized incidence ratio 1.31, 95% confidence interval 1.13 to 1.50). Also, larynx cancer among men (standardized incidence ratio 1.67, 95% confidence interval 0.95 to 2.79) and kidney cancer among women (standardized incidence ratio 3.55, 95% confidence interval 1.84 to 6.20) were found more often than expected. These excess risks were observed up to 20 years after diagnosis of bladder cancer. Therefore, bladder cancer patients experience an excess risk of smoking-related new tumors, which must be acknowledged during the initial evaluation and regular followup of such patients.

Adult↗

Risk of new primary cancer in patients with oropharyngeal cancer.

The relative risk of subsequent cancers was evaluated for a total of 9,092 patients with lip and oropharyngeal cancer recorded between 1953 and 1989 in the nationwide Finnish Cancer Registry. The observed numbers of patients were compared with those expected on the basis of the incidence rates in the Finnish population. There were 1,130 patients (12%) with a new cancer. The standardised incidence ratio (SIR) of contracting a new primary cancer was 1.2 for lip cancer patients (95% CI 1.1-1.3) and 1.4 for patients with oropharyngeal cancer (95% CI 1.2-1.4). Among lip cancer patients, a statistically significant excess risk was found for subsequent cancers in the oropharyngeal area (SIR 1.9, 95% CI 1.1-3.1), larynx (SIR 2.0, 95% CI 1.2-2.9) and lung (SIR 1.4, 95% CI 1.3-1.6), i.e. for cancers with tobacco aetiology. Among patients with oropharyngeal cancer there was an excess of lip cancer (SIR, 3.5, 95% CI 1.5-6.9), lung cancer (SIR 1.8, 95% CI 1.3-2.3) and leukaemia (SIR 2.3, 95% CI 1.0-4.3). Radiotherapy for the first primary did not increase the risk of new cancer.

Adult↗

The Helsinki Heart Study: an 8.5-year safety and mortality follow-up.

OBJECTIVES: Earlier monitoring of all symptoms, hospital admissions, cancer diagnoses and causes of death during gemfibrozil treatment had raised some suspicions which called for further follow-up. DESIGN: Close monitoring of selected, potentially adverse events amongst treated subjects after a placebo-controlled trial and comparing occurrences to those in various untreated groups. SETTING: All participants of the Helsinki Heart Study (a controlled, 5-year, multi-clinic coronary heart disease (CHD) primary prevention trial with gemfibrozil and placebo) were offered gemfibrozil treatment and twice yearly follow-up for 3.5 years. Untreated groups in the source population and national cancer statistics were utilized in comparisons. SUBJECTS: Of the 2046 dyslipidaemic men initially randomized to gemfibrozil, 2002 survivors entered the 3.5-year follow-up; of the 2035 initial placebo men, 1992 continued to be monitored. INTERVENTIONS: Gemfibrozil was chosen for the follow-up by 66.3% of the gemfibrozil-treated and 68.5% of the placebo-treated men. MAIN OUTCOME MEASURES: Gastrointestinal symptoms, surgery, strokes, cancer incidence, mortality by cause. RESULTS: Gastrointestinal symptoms remained more common in the original gemfibrozil group. After 8.5 years strokes numbered 32 (gemfibrozil) vs. 37 (placebo), violent deaths 16 vs. 14, and cancers 51 in both groups. Total mortality was equal during the original 5 years, but higher in the gemfibrozil group post-trial, leading to an 8.5 year mortality of 101 vs. placebo 83 (P = 0.19). This was mainly a result of higher cancer mortality in the gemfibrozil (30) than the placebo group (18, P = 0.08). An additional 18-month post-study registry follow-up disclosed 13 placebo and five gemfibrozil cancer deaths, altering the cancer mortality to gemfibrozil 35 vs. placebo 31 at 10 years. CONCLUSIONS: The most plausible explanation for the discrepancy between cancer incidence and cancer-specific mortality, based mainly on comparison with untreated groups, is delayed diagnosis. The increased cancer and total mortality is most probably due to chance, based on the later reversal of trends.

Adult↗

Data quality and quality control of a population-based cancer registry. Experience in Finland.

Cancer registries should pay great attention to the quality of their data, both in terms of completeness (all cancer patients in the population are registered) and accuracy (data on individual cancer patients must be correct). In addition to technical measures in the data processing, different types of checks and comparisons should be routine practice. Active research policy and ambitious, research-oriented staff with competence in medicine, biostatistics and computer science are essential in terms of maintaining good data quality.

Finland↗

Serum tumor markers CEA, CA 50, TATI, and NSE in lung cancer screening.

BACKGROUND: There are no effective means for screening for lung cancer, so the authors assessed the utility of four lung cancer tumor makers for screening. METHODS: A case-control study, nested in a cohort study based on the linkage of records of health survey examinees with Finnish Cancer Registry records, was used to test the validity of tumor markers carcinoembryonic antigen (CEA), tumor-associated trypsin inhibitor (TATI), neuron-specific enolase (NSE), and CA 50 in lung cancer screening. Ten years after health examinations, record linkage indicated that 187 men had lung cancer; 344 control subjects, matched for age, sex, and municipality were drawn from the same records. RESULTS: The data allowed assessment of the sensitivity of the marker assays at a 95% specificity level, which was highest for CEA (17% at a concentration level of 5.3 micrograms/l). Logistic discrimination analysis indicated that of the other markers, only TATI, when used in combination, improved the discriminatory power of CEA. CEA and TATI levels correlated significantly with smoking. They also showed a significant gradient toward increasing risk of lung cancer from the lowest to the highest quintiles of marker levels (for CEA, crude relative risk between the highest and lowest quintiles, 8.6). The gradient also was evident in the subgroup whose cancer had been diagnosed more than 5 years after serum specimen collection. The trend persisted, although relative risk was halved after adjustment for smoking. CONCLUSIONS: The markers do not seem to be useful tools for lung cancer screening. However, CEA and TATI levels seem to give information on cancer risk long before the clinical cancer stage, as the quintile-based analyses of marker levels indicate.

Antigens, Tumor-Associated, Carbohydrate↗

Serum antibodies and subsequent cervical neoplasms: a prospective study with 12 years of follow-up.

Approximately 40,000 blood samples drawn in 1968-1972 by the Social Insurance Institution's mobile clinic in Finland have been stored. Linking cancer incidence data obtained from the Finnish Cancer Registry with this material yielded 32 cases of cervical cancer diagnosed after drawing of the blood sample. These 32 individuals and 64 matched controls were analyzed for serum antibodies indicative of past infection with Chlamydia trachomatis, Neisseria gonorrhoeae, cytomegalovirus, Epstein-Barr virus, and herpes simplex virus type 2. After adjustment for smoking and other sexually transmitted diseases, antibodies to C. trachomatis showed the strongest association with cervical cancer (odds ratio = 5.0 (95% confidence interval 1.6-15.7)), but the numbers were too small for drawing conclusions as to the sexually transmitted diseases with which cervical cancer is most specifically associated.

Adolescent↗

Increased risk of malignant lymphoma indicated by elevated Epstein-Barr virus antibodies--a prospective study.

We estimated Epstein-Barr virus (EBV) antibody-associated relative risks (RR) of malignant lymphoma/leukemia within a cohort of 39,000 healthy Finnish adults followed up for 12 years. Antibody analyses to EBV capsid antigen (VCA), early antigen (EA), and nuclear antigens (EBNA, EBNA1, and EBNA2) were based on concomitantly evaluated ELISA techniques. No increased risk was associated with mere EBV seropositivity. However, elevated EBV EA and EBNA antibody levels were associated with a statistically significant excess risk of malignant lymphoma/leukemia (RREA = 3.4, 95 percent confidence interval [CI] = 1.0-11.0; RREBNA = 4.5, CI = 1.2-16.9). These elevated antibody responses may be due either to destruction of neoplastic EBV positive B-cells and/or to activation of latent EBV infection early in the lymphomagenesis.

Adult↗

Trends in childhood leukaemia in the Nordic countries in relation to fallout from atmospheric nuclear weapons testing.

OBJECTIVE: To obtain further information about the risks of childhood leukaemia after exposure to ionising radiation at low doses and low dose rates before or after birth or to the father's testes shortly before conception. DESIGN: Observational study of trends in incidence of childhood leukaemia in relation to estimated radiation exposures due to fallout from atmospheric nuclear weapons testing during the 1950s and 1960s. SETTING: Nordic countries. SUBJECTS: Children aged under 15 years. MAIN OUTCOME MEASURES: Incidence rates of leukaemia by age at diagnosis, sex, country, and calendar year of diagnosis or year of birth; exposure category; relation between leukaemia and exposure for children aged 0-14 and 0-4 separately. RESULTS: During the high fallout period the average estimated dose equivalent to the fetal red bone marrow was around 140 mu Sv and the average annual testicular dose 140 mu Sv. There was little evidence of increased incidence of leukaemia among children born in these years. Doses to the red bone marrow of a child after birth were higher, and during the high exposure period children would have been subjected to an additional dose equivalent of around 1500 mu Sv, similar to doses received by children in several parts of central and eastern Europe owing to the Chernobyl accident and about 50% greater than the annual dose equivalent to the red bone marrow of a child from natural radiation. leukaemia incidence and red marrow dose was not related overall, but rates of leukaemia in the high exposure period were slightly higher than in the surrounding medium exposure period (relative risk for ages 0-14: 1.07, 95% confidence interval 1.00 to 1.14; for ages 0-4: 1.11, 1.00 to 1.24). CONCLUSIONS: Current predicted risks of childhood leukaemia after exposure to radiation are not greatly underestimated for low dose rate exposures.

Adolescent↗

Herpes simplex virus type 2 infection and cervical cancer: a prospective study of 12 years of follow-up in Finland.

This study was initiated to investigate the role of past herpes simplex virus type 2 (HSV-2) infection, as determined by serum antibody analysis, in the etiology of cervical neoplasia. Two Finnish registers, the registry of the Social Insurance Institution's Mobile Clinic Survey and the Finnish Cancer Registry, were linked. About 40,000 blood samples were drawn in 1968-72 and stored by the Social Insurance Institution. According to the Cancer Registry, 32 cases of cervical carcinoma or carcinoma in situ for which serum samples were available were diagnosed in this cohort during a follow-up of 12 years (1968-81). The serum samples of these individuals and age matched controls (2:1) from the cohort were analyzed for HSV-2 antibodies. HSV-2 infection as determined by the best available HSV-2 type-specific antibody assay, glycoprotein gG2-ELISA, was not related to cervical neoplasia, i.e., the risk of cervical neoplasia among the HSV-2 positive women was not higher than that among the negative ones (smoking-adjusted relative risk = 0.5, 95 percent confidence interval = 0.2-1.6). The results do not support the hypothesis that HSV-2 is an etiologic agent for cervical neoplasia.

Adolescent↗

Serum ceruloplasmin and the risk of cancer in Finland.

The relationship between serum ceruloplasmin level and cancer incidence was investigated in a case-control study nested within a longitudinal study of 39,268 Finns participating in the Social Insurance Institution's Mobile Clinic Health Examination Survey carried out in 1968-1972. During a median follow-up of 8 years, 766 cancer cases were identified. Ceruloplasmin levels were determined from stored serum samples collected at the baseline from these cancer cases and from two matched controls per case. The overall incidence of cancer was positively associated with serum ceruloplasmin level. The association was strongest for lung cancer and other cancers related to smoking and, consequently, in males. The smoking-adjusted relative risk of lung cancer among men was 4.3 (95% confidence interval (CI) = 1.8-10.6) in the highest quintile of serum ceruloplasmin as compared with that in the lowest quintile. The corresponding relative risks for cancers related to smoking combined, and for cancers not related to smoking were 3.9 (CI = 1.9-8.4) and 0.9 (CI = 0.6-1.5), respectively. The elevated risk of lung cancer at high concentrations of serum ceruloplasmin persisted after further adjustment for several potential confounding factors such as serum levels of vitamins A and E and selenium. The risk was stronger during the first 6 years of follow-up than later, and strongest during the first 2 years. The most likely explanation of the present results thus is that high serum ceruloplasmin levels in lung cancer are mainly due to occult cancer.

Adolescent↗