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T Hakulinen

Publications and source records attributed to T Hakulinen.

At least 19 recordsLinked to original sources
PubMed2006

Age at introduction of new foods and advanced beta cell autoimmunity in young children with HLA-conferred susceptibility to type 1 diabetes.

AIMS/HYPOTHESIS: Evidence for the role of infant feeding in the development of beta cell autoimmunity is inconsistent. We set out to study the effects of breastfeeding and of age at introduction of supplementary foods on the development of beta cell autoimmunity. SUBJECTS AND METHODS: A prospective birth cohort of 3,565 infants with HLA-DQB1-conferred susceptibility to type 1 diabetes was recruited between 1996 and 2001 from two university hospital areas in Finland. Blood samples were collected at 3- to 12-month intervals to measure antibodies against islet cells, insulin, glutamate dehydroxylase and islet antigen 2. The families kept a record on the age at introduction of new foods, and for each visit completed a structured dietary questionnaire. The endpoint was repeated positivity for islet cell antibodies together with at least one of the other three antibodies. RESULTS: The overall or exclusive duration of breastfeeding was not associated with the risk of developing the endpoint. An early age at introduction of fruits and berries (< or =4 months) was related to increased risk of developing positivity for the endpoint (hazard ratio [95% CI] for earliest tertile 2.02 [1.03-3.95] and for midtertile 1.97 [1.06-3.64] compared with latest tertile >4 months). Also, introducing roots between 3 and 3.9 months (midtertile) was related to increased risk of the endpoint (hazard ratio [95% CI] for the earliest tertile 1.04 [0.57-1.90] and for midtertile 1.82 [1.19-2.79] compared with latest tertile). These associations were independent of several putative socio-demographic and perinatal confounding factors. CONCLUSIONS/INTERPRETATION: Our findings suggest that an early age at introduction of fruits and berries and roots associates independently with beta cell autoimmunity, contradicting earlier findings from smaller birth cohort studies.

Age Factors↗
PubMed2005

Age adjustment of cancer survival rates: methods, point estimates and standard errors.

We empirically evaluated the performance of a new method for age adjustment of cancer survival compared to traditional age adjustment using data from the Finnish Cancer Registry. We find that both methods provide almost identical results for absolute survival but the new method generally provides more meaningful estimates of relative survival with often a smaller standard error.

Adolescent↗
PubMed2005

Dietary manipulation of beta cell autoimmunity in infants at increased risk of type 1 diabetes: a pilot study.

AIMS/HYPOTHESIS: We aimed to assess the feasibility of a dietary intervention trial with weaning to hydrolysed formula in infants at increased risk of type 1 diabetes and to study the effect of the intervention on the emergence of diabetes-associated autoantibodies in early childhood. METHODS: We studied 242 newborn infants who had a first-degree relative with type 1 diabetes and carried risk-associated HLA-DQB1 alleles. After exclusive breastfeeding, the infants underwent a double-blind, randomised pilot trial of either casein hydrolysate (Nutramigen; Mead Johnson) or conventional cow's milk-based formula until the age of 6-8 months. During a mean observation period of 4.7 years, autoantibodies to insulin, anti-glutamic acid decarboxylase and insulinoma-associated antigen-2 were measured by radiobinding assays, and islet cell antibodies (ICA) by immunofluorescence. RESULTS: The feasibility of screening and identifying a cohort of first-degree relatives with HLA-conferred disease susceptibility, enrolling them in a dietary intervention trial and following them for seroconversion to autoantibody positivity is established. The cumulative incidence of autoantibodies was somewhat smaller in the casein hydrolysate vs control formula group, suggesting the need for a larger well-powered study. After adjustment for duration of study formula feeding, life-table analysis showed a significant protection by the intervention from positivity for ICA (p=0.02) and at least one autoantibody (p=0.03). CONCLUSIONS/INTERPRETATION: The present study provides the first evidence ever in man, despite its limited power, that it may be possible to manipulate spontaneous beta cell autoimmunity by dietary intervention in infancy.

Autoantibodies↗
PubMed2005

The influence of mammographic screening on national trends in breast cancer incidence.

Introducing an organized mammographic screening programme affects the breast cancer incidence rate in a population. The diagnosis is advanced in time, and initially, an increase will occur in the number of cases, followed by a drop in the rate when women leave the programme. The aim of this study was to quantify the potential effects that mammographic screening programmes have on breast cancer incidence. In addition, we wanted to investigate how the incidence of breast cancer varies between different birth cohorts, age groups and time periods in the five Nordic countries Finland, Denmark, Iceland, Norway and Sweden, adjusting for the effects of the screening programmes. Time trends were analysed over the period 1978-1997, using age-period-cohort models. In Sweden, the rates more than doubled (relative risk (RR)=2.20, 95% confidence interval (CI) 1.8-2.6) in women offered screening for the first time compared with women not offered screening. The risk remained elevated (RR=1.34, 95% CI 1.2-1.6) for women who were continued to be offered screening, compared with women who were not offered screening. Finally, the rates dropped (RR=0.68, 95% CI 0.6-0.8) when the women left the programme. This indicates that screening advances the time of diagnosis, which is a prerequisite to subsequent reduction in mortality. Analysis of secular trends, corrected for the influence of screening, showed that the rates in Finland increased by 13% per 5-year period, with a more modest increase in the other countries. There were strong cohort effects in all Nordic countries, and the risk seemed to be flattening for the youngest cohorts in most of the countries.

Adult↗
PubMed2004

Period analysis for 'up-to-date' cancer survival data: theory, empirical evaluation, computational realisation and applications.

Long-term survival rates are the most commonly used outcome measures for patients with cancer. However, traditional long-term survival statistics, which are derived by cohort-based types of analysis, essentially reflect the survival expectations of patients diagnosed many years ago. They are therefore often severely outdated at the time they become available. A couple of years ago, a new method of survival analysis, denoted period analysis, has been introduced to derive more 'up-to-date' estimates of long-term survival rates. We give a comprehensive review of the new methodology, its statistical background, empirical evaluation, computational realisation and applications. We conclude that period analysis is a powerful tool to provide more 'up-to-date' cancer survival rates. More widespread use by cancer registries should help to increase the use of cancer survival statistics for patients, clinicians, and public health authorities.

Cohort Studies↗
PubMed2004

Joint effects of different human papillomaviruses and Chlamydia trachomatis infections on risk of squamous cell carcinoma of the cervix uteri.

This case-control study based in Nordic serum banks evaluated the joint effects of infections with genital human papillomavirus (HPV) types, and Chlamydia trachomatis in the aetiology of cervical squamous cell carcinoma. Through a linkage with the cancer registries, 144 cases were identified and 420 controls matched to them. Exposure to past infections was defined by the presence of specific IgG antibodies. The odds ratio (OR) for the second-order interaction of HPV16, HPV6/11 and C. trachomatis was small (1.0) compared to the expected multiplicative OR, 57, and the additive OR, 11. The interactions were not materially different among HPV16 DNA-positive squamous cell carcinomas. When HPV16 was replaced with HPV18/33 in the analysis of second-order interactions with HPV6/11 and C. trachomatis, there was no evidence of interaction, the joint effect being close to the expected additive OR. Possible explanations for the observed antagonism include misclassification, selection bias or a true biological phenomenon with HPV6/11 and C. trachomatis exposures antagonizing the carcinogenic effects of HPV16.

Adult↗
PubMed2003

Differences in colorectal cancer survival between European and US populations: the importance of sub-site and morphology.

A previous study has shown a lower survival for colorectal cancer in Europe than in the United States of America (USA). It is of interest to examine the extent to which anatomical location and morphological type influence this difference in colorectal cancer survival. We analysed survival for 151,244 European and 53,884 US patients diagnosed with colorectal cancer aged 15-99 years during the period of 1985-1989, obtained from 40 cancer registries that contribute to the EUROCARE study from 17 countries, and nine Surveillance, Epidemiology and End-Results (SEER) registries in the USA. Cases included in the analysis were first primary malignant tumours (ICD-O behaviour code 3 or higher). Relative survival was estimated to correct for competing causes of mortality. The Hakulinen-Tenkanen multiple regression approach was used to examine the prognostic impact of sub-site and ICD-O histology codes. Relative excess risks (RERs) derived from this approach estimate the extent to which the hazard of death differs from that in a reference region after adjustment for mortality in the general population. In order to explore geographical variation, we defined three groups of European registries within which survival rates were known to be broadly similar. The proportion of cases with unspecified sub-site was higher in Europe than the USA (10% versus 2%), but sub-site distributions were broadly similar in the two populations. With the exception of appendix, 5-year survival was 13-22% higher in the USA than in Europe for each anatomical sub-site. The proportion of non-microscopically-verified cases was higher in Europe than the USA (16 versus 3%). Adenocarcinomas arising in a polyp (ICD-O-2 8210, 8261, 8263) were more frequent in the USA than Europe (13 versus 2%). Five-year survival was higher in the USA than Europe for each morphological group, with the exception of non-microscopically-verified cases. When age, gender and sub-site were considered, RERs ranged from 1.52 to 2.40 for the European populations (with the USA as a reference). After inclusion of morphology codes, the range of RERs fell to between 1.28 and 1.86, mainly because of the high frequency of adenocarcinoma in polyps in the USA. This analysis suggests that the large survival advantage for colorectal cancer patients in the USA can only marginally be explained by differences in the distribution of sub-site and morphology. The main explanatory difference is the proportion of adenocarcinoma in polyps.

Adenocarcinoma↗
PubMed2003

Cancer prevalence in Northern Europe: the EUROPREVAL study.

BACKGROUND: Information on cancer prevalence is of importance for health planning and resource allocation, but is not always available. In order to obtain such data in a comparable way a systematic evaluation of cancer prevalence in Europe was undertaken within the EUROPREVAL project. PATIENTS AND METHODS: Standardised data were collected from 38 population-based registries on almost 3 million cancer patients diagnosed between 1970 and 1992. The prevalence of 11 specific cancer types was estimated at the index date of 31 December 1992. This study deals with the northern countries Denmark, Estonia, Finland, Iceland and Sweden. RESULTS: There were large differences between these countries, Sweden having the highest prevalence rate of 3050 per 100 000 and Estonia the lowest, 1339 per 100 000. This difference is mainly due to a high proportion of cancers with favourable prognosis such as breast cancer, prostate cancer and melanoma, better survival and longer life expectancy in Sweden, whereas Estonia has a higher proportion of stomach and lung cancer with poor prognosis, worse survival and much shorter life expectancy, especially for males. For most tumour types, the Nordic countries did better than Estonia. There are indications that cancer patients in Estonia, as well as in Denmark, have a more advanced stage at diagnosis and that the Estonian health-care system is less efficient. CONCLUSIONS: Despite many similarities and a common historical background, the northern countries in Europe that participated in the EUROPREVAL study display quite different cancer patterns and prevalence. Reasons for these variations are discussed.

Adolescent↗
PubMed2003

European health systems and cancer care.

INTRODUCTION: Data on the survival of all incident cases collected by population-based cancer registries make it possible to evaluate the overall performance of diagnostic and therapeutic actions on cancer in those populations. EUROCARE-3 is the third round of the EUROCARE project, the largest cancer registry population based collaborative study on survival in European cancer patients. The EUROCARE-3 study analysed the survival of cancer patients diagnosed from 1990 to 1994 and followed-up to 1999. Sixty-seven cancer registries of 22 European countries characterised by differing health systems participated in the study. This paper includes essays providing brief overviews of the state and evolution of the health systems of the considered countries and comments on the relation between cancer survival in Europe and some European macro-economic and health system indicators, in the 1990s. OVERVIEW OF THE EUROPEAN HEALTH SYSTEMS: The European health systems underwent a great deal of reorganisation in the last decade; a general tendency being to facilitate expanding involvement of the private sector in health care, a process which occurred mainly in the eastern countries (i.e. the Czech Republic, Estonia, Poland, Slovakia and Slovenia). In contrast, organisational changes in the northern European countries (i.e. Denmark, Iceland, Finland and Sweden) tended to confirm the established public sector systems. Other countries, including the UK and some southern European countries (i.e. England, Scotland, Wales, Malta and Italy) have reduced the public role while the systems remain basically public, at least at present. Our findings clearly suggest that cancer survival (all cancer combined) is related to macro-economic variables such as the gross domestic product (GDP), the total national (public and private) expenditure on health (TNEH) and the total public expenditure on health (TPEH). We found, however, that survival is related to wealth (GDP), but only up to a certain level, after which survival continues to be related to the level of health investment (both TNEH and TPEH). According to the Organisation for Economic Co-operation and Development (OECD), the TNEH increased during the 1990s in all EUROCARE-3 countries, while the ratio of TPEH to TNEH reduced in all countries except Portugal. CONCLUSIONS: Cancer survival depends on the widespread application of effective diagnosis and treatment modalities, but our enquiry suggests that the availability of these depends on macro-economic determinants, including health and public health investment. Analysis of the relationship between health system organisation and cancer outcome is complicated and requires more information than is at present available. To describe cancer and cancer management in Europe, the European Cancer Health Indicator Project (EUROCHIP) has proposed a list of indicators that have to be adopted to evaluate the effects on outcome of proposed health system modifications.

Community Health Planning↗
PubMed2003

Epidemiological trends of colorectal cancer in the Nordic countries.

Cancer of the colorectum is the second most common cancer in the Nordic countries, after breast cancer. In this report, following Møller et al. (Eur J Cancer Prev 2002; 11 Suppl: S1-96), trends in incidence of colon and rectum cancers in the five Nordic countries are presented from 1958-1962 to 1993-1997, with future predictions for 2003-2007. The data originate from population-based cancer registries in each of the Nordic countries. Two thirds of the cases are colon cancers and one-third rectum cancers. From 1958-1962 to 1993-1997, the incidence of colon cancer has increased in all Nordic countries and the rates are predicted to increase further in Finland, Iceland, and Norway. The incidence rate of rectum cancer has increased slightly in Finland, Iceland, and Sweden, whereas the rate has decreased steadily in Denmark, originally a high-incidence country. In Norway the rates have increased substantially in both genders. Marked differences exist between individual Nordic countries in colorectal cancer incidence trends and known dietary or other life style associated factors cannot fully explain them.

Colonic Neoplasms↗
PubMed2002

Cancer-specific survival of patients with multiple cancers: an application to patients with multiple breast cancers.

In the analysis of cause-specific survival, the causes of death must be known. For single-cancer patients with a known cause of death, the estimation of the cause-specific survival rate is straightforward. For multiple-cancer patients with two primary cancers, however, the analysis of cause-specific survival rates is more complex, particularly if the cancers are of the same primary site. In these situations, a concept of cancer-specific survival may also be distinguished from cause-specific survival. Cancer-specific survival rates are studied here by introducing two models, the primary one where the death from cancer is attributed to one of the cancers, and an alternative where such an attribution is not necessary. The models are illustrated using data on patients with multiple breast cancers. The model-based survival rates are compared with each other and with the corresponding relative survival rates based on analogous modelling of relative survival. The results show that for the subsequent breast cancer, the cancer-specific survival rates based on the alternative, where the distinction between the cancers as a cause of death was not necessary, tended to be higher than those based on that distinction. It is thus possible that the subsequent cancer was too often coded as a cause of death, particularly when being localized at diagnosis.

Adult↗
PubMed2002

A computer program for period analysis of cancer patient survival.

Monitoring of long-term survival rates, which is now routinely performed by many cancer registries throughout the world, should be as up-to-date as possible. A few years ago, a new method of survival analysis, denoted period analysis, has been proposed which provides more up-to-date estimates of long-term survival rates than traditional survival analysis by exclusively reflecting the survival experience of patients within a recent calendar period. However, application of this method has so far been hindered by the lack of pertinent computer programs. In this paper, we present a simple and easy-to-use computer program (SAS macro) that enables one to carry out period analysis (as well as conventional analysis) of both absolute and relative survival rates with the type of data commonly available in population-based cancer registries. We illustrate application of the program with examples from the nationwide Finnish Cancer Registry.

Female↗
PubMed2002

Cancer prevalence in European registry areas.

BACKGROUND: Information on cancer prevalence is of major importance for health planning and resource allocation. However, systematic information on cancer prevalence is largely unavailable. MATERIALS AND METHODS: Thirty-eight population-based cancer registries from 17 European countries, participating in EUROPREVAL, provided data on almost 3 million cancer patients diagnosed from 1970 to 1992. Standardised data collection and validation procedures were used and the whole data set was analysed using proven methodology. The prevalence of stomach, colon, rectum, lung, breast, cervix uteri, corpus uteri and prostate cancer, as well as of melanoma of skin, Hodgkin's disease, leukaemia and all malignant neoplasms combined, were estimated for the end of 1992. RESULTS: There were large differences between countries in the prevalence of all cancers combined; estimates ranged from 1170 per 100000 in the Polish cancer registration areas to 3050 per 100000 in southern Sweden. For most cancers, the Swedish, Swiss, German and Italian areas had high prevalence, and the Polish, Estonian, Slovakian and Slovenian areas had low prevalence. Of the total prevalent cases, 61% were women and 57% were 65 years of age or older. Cases diagnosed within 2 years of the reference date formed 22% of all prevalent cases. Breast cancer accounted for 34% of all prevalent cancers in females and colorectal cancer for 15% in males. Prevalence tended to be high where cancer incidence was high, but the prevalence was highest in countries where survival was also high. Prevalence was low where general mortality was high (correlation between general mortality and the prevalence of all cancers = -0.64) and high where gross domestic product was high (correlation = +0.79). Thus, the richer areas of Europe had higher prevalence, suggesting that prevalence will increase with economic development. CONCLUSIONS: EUROPREVAL is the largest project on prevalence conducted to date. It has provided complete and accurate estimates of cancer prevalence in Europe, constituting essential information for cancer management. The expected increases in prevalence with economic development will require more resources; allocation to primary prevention should therefore be prioritised.

Adolescent↗
PubMed2002

Parametric mixture model for analysing relative survival of patients with multiple cancers.

BACKGROUND: This study aimed to provide a parametric mixture model for analysing relative survival and cure rates of patients with multiple cancers. METHODS: A new model was introduced by extending a parametric mixture model on relative survival of patients with a single cancer. The model was applied to empirical data on lung cancer as a first and second tumour after a first localised colorectal cancer. RESULTS: Survival and cure from subsequent cancer are estimatable with the parametric mixture model on relative survival of patients with multiple cancers. Survival from lung cancer does not differ between the first and second tumour, but there is suggestive evidence that survival from second lung cancer is higher than that from the first lung cancer. DISCUSSION: Relative survival analysis of patients with multiple cancers can be extended to incorporate cure rates and excess hazards related to the individual cancers. Prognostic factors can be included in the model.

Adult↗
PubMed2002

Relative survival of patients with subsequent cancer.

BACKGROUND: With the increasing numbers of patients with multiple primary cancers, survival from subsequent cancers is of growing interest. The majority of the analyses on the subject so far have, however, suffered from methodological difficulties. METHODS: A new model is now proposed for estimating relative survival of patients with subsequent primary cancer. The model is an extension to that proposed earlier by Estève et al. for estimating relative survival using individual patient data. The model is illustrated with real data on patients with one or two primary breast cancers and used in comparing the excess hazards between first and subsequent breast cancer. RESULTS: For patients with multiple cancers, the traditional analysis of relative survival can be made cancer-specific. The excess hazards are different between the first and subsequent breast cancer: The excess hazard of the subsequent breast cancer tends to decrease with increasing age when compared to the corresponding hazard of the first breast cancer. CONCLUSIONS: Relative survival of patients with subsequent cancer can be modelled facilitating studies on different hypothesis on the excess hazards of a first and subsequent cancer.

Adult↗