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Showing papers by "Timo Hakulinen published in 1999"


Journal ArticleDOI
TL;DR: A significant positive association was observed between intake of NDMA and subsequent occurrence of colorectal cancer with a relative risk between the highest and lowest quartiles of intake of 2.12 [95% confidence interval (CI) 1.04–4.33].
Abstract: N-nitroso compounds are potent carcinogens detected in foodstuffs. The importance of dietary nitrosamines in relation to human cancer development is, however, uncertain. We studied the relationship between intake of nitrates, nitrites and N-nitrosodimethylamine (NDMA) and risk of cancers of the gastro-intestinal tract in a cohort of 9,985 adult Finnish men and women. During a follow-up period of up to 24 years, 189 gastro-intestinal cancer cases were diagnosed in the cohort, initially free from cancer. Intake of nitrate, nitrite and NDMA were estimated, based on food-consumption data from a 1-year dietary history interview covering the total diet of the participants. A significant positive association was observed between intake of NDMA and subsequent occurrence of colorectal cancer with a relative risk (RR) between the highest and lowest quartiles of intake of 2.12 [95% confidence interval (CI) 1.04-4.33]. Of various sources of N-nitroso compounds, intake of smoked and salted fish was significantly (RR = 2.58, 95% CI 1.21-5.51) and intake of cured meat was non-significantly (RR = 1.84, 95% CI 0.98-3.47) associated with risk of colorectal cancer. No similar association was observed for intake of other fish or other meat. No significant associations were observed between NDMA intake and cancers of the head and neck combined or of the stomach or between nitrate or nitrite intake and risk of cancers of the gastro-intestinal tract. Our results are in line with the idea that N-nitroso compounds can induce colorectal cancer in humans.

300 citations


Journal ArticleDOI
TL;DR: The increasing survival rates reflect improvements that have taken place in various areas of cancer control, from health education and early diagnosis to treatment and aftercare.
Abstract: This is a study on the survival of all Finnish cancer patients diagnosed between 1953 and 1974. Data are from the Finnish Cancer Registry. Nearly all the 200000 cancer patients studied were followed up to death or the end of 1974. Factors investigated include primary site of cancer age and sex calender period and treatment. Relative survival rate and estimated mean length of life are used as the measures of survival. (ANNOTATION)

198 citations


Journal ArticleDOI
TL;DR: An application of a parametric mixture model to relative survival rates of colon cancer patients from the Finnish population-based cancer registry is proposed, including major survival determinants as explicative covariates and support the hypothesis that observed survival trends are really due to a real prognostic gain for more recently diagnosed patients.
Abstract: The interest in estimating the probability of cure has been increasing in cancer survival analysis as the curability of many cancer diseases is becoming a reality. Mixture survival models provide a way of modelling time to death when cure is possible, simultaneously estimating death hazard of fatal cases and the proportion of cured case. In this paper we propose an application of a parametric mixture model to relative survival rates of colon cancer patients from the Finnish population-based cancer registry, and including major survival determinants as explicative covariates. Disentangling survival into two different components greatly facilitates the analysis and the interpretation of the role of prognostic factors on survival patterns. For example, age plays a different role in determining, from one side, the probability of cure, and, from the other side, the life expectancy of fatal cases. The results support the hypothesis that observed survival trends are really due to a real prognostic gain for more recently diagnosed patients.

182 citations


Journal ArticleDOI
TL;DR: The results are in line with the concept that HPV‐specific immunity protects against SCC and support primary prevention of SCC by vaccination against the HPVs.
Abstract: Human papillomavirus (HPV) types 16 and 18 are the major risk factors for cervical carcinoma, whereas HPV types 6 and 11 cause benign genital lesions. We wanted to study the joint effect of simultaneous infections with the oncogenic and non-oncogenic HPV types on risk of subsequent development of cervical carcinoma. A cohort of 530,000 women who had donated blood samples to Nordic serum banks between 1973 and 1994 was followed up by linkage to national cancer registries. We identified 182 prospective cases with invasive cervical carcinoma and selected 538 matched controls at random. HPV 6, 11, 16, 18 and 33 seropositivity was used as a marker for the different HPV infections, and seropositivity for Chlamydia trachomatis and cotinine were used as markers for risk-taking sexual behavior and smoking respectively. The adjusted odds ratio (OR) of cervical squamous-cell carcinoma (SCC) was 2.2 for HPV6/11 among HPV16 seronegatives and 5.5 for HPV16 among HPV6/11 seronegatives. Assuming multiplicative joint effect, the expected OR for seropositivity to both HPV6/11 and HPV16 would have been 12, but the observed OR was 1.0. The antagonistic interaction was statistically significant (p = 0.001) and present also under deterministic considerations of possible misclassification bias. Antagonistic interactions were also detected for combinations of HPV16 and HPV18 and of HPV16 and HPV33. The results are in line with the concept that HPV-specific immunity protects against SCC and support primary prevention of SCC by vaccination against the HPVs.

87 citations


Journal ArticleDOI
TL;DR: A poor survival rate for small cell anaplastic lung carcinoma compared with all other morphologies was confirmed, and the main factor in the lower survival rate in Denmark is unfavourable stage distribution.
Abstract: Danish lung cancer patients diagnosed during 1983-1987 experienced 5-yr relative survival rates 2-7% inferior to patients in the other Nordic countries, despite the similarity of cancer registration and healthcare systems in the Nordic countries. Is the inferior relative survival in Denmark due to differences in morphology or stage of lung cancers? The present study compared in detail the survival of 92,719 patients diagnosed with lung cancer during 1978-1992 in Denmark, Finland, and Norway. In particular, differences in morphology and extent of disease were studied. A poor survival rate for small cell anaplastic lung carcinoma compared with all other morphologies was confirmed. However, this could not explain the relative survival differences observed between countries. Extent of disease was the most important predictor of survival. Part of the observed survival differences could be explained by a less favourable stage distribution in Denmark, combined with a slightly lower relative survival rate for those with metastatic disease. Differences in treatment are unlikely to explain the findings, although delays in diagnosing and treating patients in Denmark compared with neighbouring countries could partially explain the lower patient survival in Denmark. In conclusion, the main factor in the lower survival rate in Denmark is unfavourable stage distribution.

37 citations


Journal ArticleDOI
TL;DR: The effects of primary site, sex, age, stage and histological type on cancer patient survival were analysed on the basis of the population-based material of the Finnish Cancer Registry from 1985 to 1994 and trends in survival were constructed.
Abstract: The effects of primary site, sex, age, stage and histological type on cancer patient survival were analysed on the basis of the population-based material of the Finnish Cancer Registry from 1985 to 1994. In addition, trends in survival were constructed for the period 1955-1994. Detailed site-specific data are published as Supplement 12 to Vol. 38 of Acta Oncologica. Within a given site, the survival differences by gender were not large. However, because of different site distributions, the average prognosis for female patients, all sites taken together, was superior to that of males: the 5-year relative survival rates (RSR) were 58% and 43%, respectively. In general, older patients had a poorer outcome compared with younger patients (partly because of different stage and histology distributions). Stage was a strong determinant of patient survival. In some cancers with a poor average prognosis the 5-year RSR for localized tumours was reasonable, e.g. 61% for stomach cancer, males, 34% for gallbladder cance...

34 citations


Journal ArticleDOI
TL;DR: Cervical screening can explain the trends in cervical cancer survival: this identifies premalignant lesions, reduces incidence and selectively prevents less aggressive cancers.
Abstract: Objectives: To analyze cervical cancer survival trends in 10 European countries using models that estimate the proportion of cured patients (having the same life expectancy as the general population) and the survival of fatal cases (who die from cervical cancer) Methods: We considered 40,906 cases diagnosed over 12 years (1978–89) collected from cancer registries participating in EUROCARE Results: From 1978 to 1989, 5-year relative survival in Europe improved (60%→63%) The proportion of cured patients increased slightly but significantly (53%→55%, p = 005) For countries with poorer survival at the end of the 1970s the proportion of cured patients increased faster than average, particularly evident in England (49%→56%) and Scotland (44%→53%) By contrast, in Finland, Sweden and Germany with organized screening, 5-year survival and cure rate did not improve, but incidence declined to very low levels Conclusions: Cervical screening can explain the trends in cervical cancer survival: this identifies premalignant lesions, reduces incidence and selectively prevents less aggressive cancers The decreased proportion of the latter means that survival does not improve in countries with low incidence of cervical cancer The increased proportion of cured patients with time shows that survival improvement was not due simply to earlier diagnosis with no patient advantage

25 citations


Journal ArticleDOI
TL;DR: Retinol might act as an effect modifier of the HPV-associated risk for cervical cancer; exposed women may require adequate levels for immunologic surveillance of HPV.
Abstract: Nutritional factors have been associated with risk of cervical cancer, but it is unclear whether the associations are of etiological significance or secondary to human papillomavirus (HPV) exposure. A delineation of this question requires a prospective study with invasive cancer as the end point. We conducted a nested case-control study in Finland and Sweden within a joint cohort of 405,000 women followed up for, on average, 4 years. Blood samples from 38 prospective cases of invasive cervical cancer diagnosed between 1985 and 1994 and 116 controls matched for age, country, and sample storage time were available for the study. Levels of retinol or unoxidized a-tocopherol in the blood were not risk factors for cervical cancer. However, joint-effect analysis of low levels of retinol disclosed statistically significant (p = 0.023) synergistic (more than multiplicative) interaction with HPV (HPV16, HPV18, or HPV33) seropositivity (observed relative risk = 2.6, 95% confidence interval = 0.7-8.8, expected relat...

23 citations