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Biomedical subjects

Kari Hemminki

Publications and source records attributed to Kari Hemminki.

At least 199 records · Page 11Linked to original sources
PubMed2003

Time to pregnancy among the wives of Finnish greenhouse workers.

OBJECTIVES: This study investigated the possibility of men's work in greenhouses and their exposure to pesticides being associated with reduced fertility. METHODS: A study on time to pregnancy was conducted among the families of Finnish male greenhouse employers and employees. Exposure to pesticides was assessed on the basis of questionnaire information and data gathered from the enterprises. Fecundability density ratios (FDR) for occupational exposure were calculated with discrete proportional hazards regression analyses. RESULTS: After three mailings, 578 (43%) couples participated. Fecundability was suggestively decreased for exposed greenhouse workers who were inefficiently protected, with FDR values of 0.67 [95% confidence interval (95% CI) 0.33-1.35], 0.92 [95% CI 0.45-1.88] and 0.77 [95% CI 0.46-1.29] for high exposure, moderate exposure and low exposure, respectively, as compared with unexposed greenhouse workers. The exposed men who efficiently used personal protective equipment were as fertile as the unexposed greenhouse workers. Exposure to pyrethroids (FDR 0.40, 95% CI 0.19-0.85) was related to decreased fecundability. Suggestive associations were observed for organophosphates (FDR 0.70, 95% CI 0.42-1.17) and carbamates (FDR 0.55, 95% CI 0.27-1.11). CONCLUSIONS: The findings of the study provide limited support for the hypothesis that exposure to pesticides is associated with reduced fertility. The findings for pyrethroids, organophosphates, and carbamates can serve as a basis for a hypothesis for future studies.

Adult↗
PubMed2003

Detecting homozygous deletions in the CDKN2A(p16(INK4a))/ARF(p14(ARF)) gene in urinary bladder cancer using real-time quantitative PCR.

PURPOSE: 9p21 is a major target in the pathogenesis of human urinary bladder cancer. The locus harbors the CDKN2A/ARF tumor suppressor gene, which encodes two cell cycle regulatory proteins cyclin dependent kinase 2A (p16(INK4a)) and alternate reading frame (p14(ARF)). We have designed a real-time quantitative PCR (QPCR) application to study homozygous deletion (HD) of CDKN2A/ARF in 186 urinary bladder cancer patients. EXPERIMENTAL DESIGN: Real-time QPCR, based on simultaneous amplification of ARF and a reference gene, GAPDH, was developed and evaluated in three melanoma cell lines with HDs at the CDKN2A/ARF locus (IGR-1, SK-MEL-5, and WM-266-4). In addition, loss of heterozygosity was analyzed at the D9S942, D9S1748, and D12S99 markers. Mutation analysis of the CDKN2A/ARF gene was performed using single-strand conformational polymorphism and sequencing. Results from the present investigation were combined with previous p53 analysis of the same urinary bladder neoplasms. RESULTS: Real-time QPCR analysis showed 26 (14%) HDs, 22 (12%) hemizygous deletions, and 3 (2%) multiple duplications. Loss of heterozygosity was determined in 30 (22%) cases at the D9S942 locus, which is located between E1alpha and E1beta of the CDKN2A/ARF gene. No association was established between occurrence of genetic aberrations at 9p21 and tumor stage or grade, supporting previous suggestions that CDKN2A/ARF inactivation is an early event in bladder carcinogenesis. CONCLUSIONS: We have established a fast and efficient method for detection of HDs. Our data support the notion that inactivation, including HDs, of CDKN2A/ARF is an early event in transitional cell carcinoma. We observed separate and specific targeting of the CDKN2A and ARF genes, respectively, and that simultaneous inactivation of ARF and p53 occurs.

Carcinoma, Transitional Cell↗
PubMed2003

Level of education and the risk of cancer in Sweden.

It is well known that certain cancers have shown clusteringin educational and socioeconomic groups, but recent comprehensive data on clustering by education are limited. We determined standardized incidence ratios (SIRs), adjusted for several variables, for cancer among men and women in six educational groups based on the Swedish Family-Cancer Database. People were identified with a certain educational background in the census of year 1970; the comparison group was the largest group, those with <9 years of education. Cancers were followed from years 1971 to 1998. Total cancer risks did not differ much, but at individual sites, the trend was significant, either increasing or decreasing over all educational groups (for 27 of 29 male and 28 of 31 female cancers). University graduates had a decreased risk of tobacco-, alcohol-, and genital infection-related cancers, but male graduates had an excess of colon, prostate, squamous cell skin, nervous system cancer, and melanoma. Male graduates showed a low SIR of 0.50 for stomach cancer and a high SIR of 1.89 for melanoma; female graduates showed a low SIR of 0.43 for lung and cervical cancer and a high SIR of 1.57 for melanoma. The overall weighted population attributable fraction for educational level was 13.8% for men and 16.7% for women, and it was highest, >50%, for stomach cancer in both genders and for cervical and anal cancer in women.

Educational Status↗
PubMed2003

Lifestyle and cancer: effect of widowhood and divorce.

Limited data are available on the possible changes in cancer risk brought about by widowhood and divorce, an increasing segment of the population. We calculated standardized incidence ratios (SIRs) for cancer among 47,000 widows/widowers and 60,000 divorced people, based on the Swedish Family-Cancer Database. Persons had to be identified with the same civil status in the census of years 1960 and 1970; the comparison group was married people according to the same censuses. Cancers were followed from years 1971 to 1998. Both increased and decreased SIRs were found, and a consistent pattern emerged. The effects on the divorced were always stronger than those in widows/widowers, irrespective of the direction of the effect. Every significant SIR for a cancer site in widows/widowers was accompanied by a more deviant and significant SIR in the divorced. SIRs between divorced men and women (r=0.83, P<0.0001) and between widows and divorcees correlated (r=0.70, P<0.0001). The overall cancer risk for the divorced was 0.92-0.94, and it was a balance between increased risks at tobacco-, alcohol-, and human papilloma virus-related sites, and decreased risks at most other sites. The data suggest that the changes in lifestyle on the loss of a spouse impact on the incidence of almost every type of cancer. The effects were so large that a failure to consider marital status in epidemiological studies may be a source to bias. Understanding these lifestyle changes may provide new insight in cancer prevention.

Alcohol Drinking↗
PubMed2003

Familial risks in nervous system tumors.

We used the nationwide Swedish Family-Cancer Database to analyze the risk for nervous system tumors in offspring through parental and sibling probands. Among 0-68-year-old offspring, close to 11000 patients with a nervous system tumor were identified in years 1961 to 2000, among whom 199 had a parent diagnosed with a nervous system tumor. Brain tumors constituted 86% of all tumors, and astrocytoma was the main histological type, representing half of all cases. Standardized incidence ratios (SIRs) for familial risk were only increased for brain tumors of meningioma, astrocytoma, and hemangioblastoma histology. When parents were diagnosed with tumors of the same histology, the SIRs for offspring were 3.06, 2.19, and 165 for meningioma, astrocytoma, and hemangioblastoma, respectively. Among siblings, the SIRs were 4.41, 3.20, and 61. Age-specific analysis of familial astrocytoma revealed three distinct components, one < 10 years, the second approximately age 30 years, and the third at age >60 years. The kappa test was used to assess the likelihood of an identical histology in two family members. The occurrence of hemangioblastoma was completely determined among the siblings, and the kappa value was 1.00. Meningiomas were also moderately ordered among the siblings, but astrocytomas were less determined. Many syndromes are known in which nervous system tumors are manifestations, including hemangioblastoma, recognized as part of von Hippel-Lindau disease. Yet, it is likely that many brain astrocytoma, meningioma, and mixed families represent yet unknown heritable conditions.

Adolescent↗
PubMed2002

Gender effects in familial cancer.

Very limited data are available on sex ratios in familial cancer. Such data would be valuable in the assessment of sex chromosome effects and of interactions between background and familial rates. We used the nationwide Swedish Family-Cancer Database on 10.2 million individuals and over 1 million neoplasms to analyze familial risks for male and female offspring by paternal and maternal concordant cancer. Sex ratios for familial cancer were derived for cancer at 15 sites shared by men and women. At 14 sites the sex ratio (male/female) for familial relative risk ranged between 0.78 and 1.41, with no evidence of sex preference, suggesting that sex chromosomes do not contribute to a noticeable extent to familial risks. Furthermore, in cancers where the background incidence varied extensively by sex, such as bladder cancer (sex ratio 2.82) and nonthyroid endocrine tumors (0.65), the familial effect was proportionate to the background incidence and the familial sex ratio was close to unity. In thyroid cancer, the familial sex ratio was 2.48 (1.54-3.98) and the background incidence ratio was 0.31. This was the first evidence of an inverse sex ratio in primary cancer, i.e., higher familial risk in the gender of low background risk. The high familial ratio, 2.85 (95% CI: 1.35-6.03), was due to thyroid adenocarcinoma, encompassing both papillary and follicular types.

Adenocarcinoma↗
PubMed2002

Age specific and attributable risks of familial prostate carcinoma from the family-cancer database.

BACKGROUND: Familial risks by proband status and age are useful for clinical counseling, and they can be used to calculate population-attributable fractions (PAFs), which show the proportion of disease that could be prevented if the cause could be removed. METHODS: The authors used the nationwide Swedish Family-Cancer Database on 10.2 million individuals and 182,104 fathers and 3710 sons with medically verified prostate carcinoma to calculate age specific familial standardized incidence ratios (SIRs) with 95% confidence intervals (95%CI) and familial PAFs for prostate carcinoma in sons ages 0-66 years. RESULTS: The incidence of prostate carcinoma was doubled between the years 1961 and 1998. The familial SIRs for prostate carcinoma were 2.38 (95%CI, 2.18-2.59) for men with prostate carcinoma in the father only, 3.75 (95%CI, 2.73-4.95) for men with prostate carcinoma in a brother only, and 9.44 (95%CI, 5.76-14.03) for men with prostate carcinoma in both a father and a brother. The corresponding familial PAFs were 8.86%, 1.78%, and 0.99%, respectively, yielding a total PAF of 11.63%. Age specific risks were shown for the same proband histories. The SIR was 8.05 for prostate carcinoma before age 55 if a brother had been diagnosed before that age. If, in addition, a father was diagnosed at any age, then the SIR was 33.09. CONCLUSIONS: The authors recommend that having a brother who is diagnosed with prostate carcinoma before age 55 years or having a brother and father who are diagnosed at any age are indications to screen for prostate carcinoma. The familial PAF of prostate carcinoma among a population of sons ages 0-66 years was 11.63%.

Age Factors↗
PubMed2002

New aspects in the biomonitoring of occupational exposure to styrene.

OBJECTIVE: Based on our previous studies we analysed DNA and haemoglobin adducts, single-strand breaks in DNA, chromosomal aberrations and HPRT mutant frequencies in styrene-exposed workers, in relation to employment time, with respect to markers of individual susceptibility. In our study the risk assessment of genotoxic styrene in occupationally exposed humans is reviewed in the light of adaptation and/or population selection. Various styrene-induced DNA adducts (representing important integral measures of DNA damage) are discussed as potential powerful biomarkers of styrene exposure, with respect to DNA repair. METHODS: The complexity of followed markers required multiple methodological approaches, including modified (32)P-post-labelling assay, PCR-based methods for genotyping, cytogenetic analysis, T-cell cloning assay, comet assay and tests for DNA repair capacity, and statistical tests. RESULTS: Haemoglobin and DNA adducts, single-strand breaks in DNA, chromosomal aberrations and mutant frequencies at the HPRT gene were assessed with respect to the duration of exposure. No apparent accumulation of these biomarkers was found to be dependent on the years of employment, suggesting that adaptive processes play a role in chronically exposed workers. Statistically significant differences between the exposed and control individuals were found for the deduced epoxide hydrolase activity ( P=0.041) and the frequency of heterozygous Ala/Val genotype in GSTP1, exon 5 ( P=0.025). Significantly increased DNA repair capacity was found in styrene-exposed laminators compared with control individuals. CONCLUSIONS: In the light of present knowledge well-designed population studies on styrene genotoxicity are needed. Such studies should cover important areas of individual susceptibility (metabolising and repair enzymes, distributions of genetic polymorphisms) and possible role of adaptation, as well as the crucial role of DNA repair. Additionally, genotoxic effects of in-vivo formed 3,4-styrene oxide should be also addressed.

DNA Adducts↗
PubMed2002

Attributable risks for familial breast cancer by proband status and morphology: a nationwide epidemiologic study from Sweden.

Population attributable factions (PAFs) show the proportion of the disease that could be prevented if the cause could be removed. The PAF for familial breast cancer has not been precisely determined. We used the nationwide Swedish Family-Cancer Database on 10.2 million individuals and 190,000 mothers' and 26,000 daughters' breast cancers to calculate familial standardized incidence ratios (SIRs), proportion of cases with a family history and familial PAFs for all invasive and in situ and morphology-specific breast cancers in daughters who were 0-66 years old. The data were calculated by mother only, sister only or both as probands. More than 5,500 familial breast cancers were recorded. The familial SIRs for all invasive breast cancer were 1.79 by breast cancer in the mother only, 2.03 by breast cancer in a sister only and 2.82 by breast cancer in both a mother and sister. The familial PAFs were 3.61, 3.01 and 0.43%, respectively, giving a total PAF of 7.05%. Age-specific risks were shown for the mother and sister history of breast cancer. The PAF values decreased by age when the daughter had a mother history of breast cancer but not when she had a sister history. PAFs did not depend on the morphologic type of breast cancer. The data show that the familial PAF of breast cancer among a 0-66-year-old population of daughters was 7% and independent of the morphologic type. If contribution from the paternal side was allowed for, the PAF would be 11%.

Adolescent↗
PubMed2002

Cancer risks in twins: results from the Swedish family-cancer database.

Twin studies on cancer have addressed two general questions, one about the possible carcinogenic effects of twinning and the second about heritable effects of cancer. The first question is answered by comparing the occurrence of cancer in twins to that in singletons; the second is answered in probandwise analysis of monozygotic twins compared to dizygotic twins or siblings. We used the nationwide Swedish Family-Cancer Database on 10.2 million individuals and 62,574 0-66-year-old twins to calculate standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for all main cancer compared to cancer in singletons. In probandwise analysis, the SIR was calculated for the co-twin of an affected twin. The overall risk of cancer in same or opposite sex twins was at the level of the risk for singletons. Testicular cancer was increased among same sex twins and all twins to an SIR of 1.43. Melanoma was decreased in these groups of twins to an SIR of 0.84. Some other cancer sites were increased or decreased in some groups of twins, but none in all twins. The SIR of breast cancer was 1.01 and 1.04 in same and opposite sex twins, respectively. Probandwise analysis showed increased risks for Hodgkin's disease in males and breast cancer and childhood acute lymphoid leukemia among females. The data on this unselected population of twins suggest that twinning per se is not a risk factor of cancer. However, because twins are smaller than singletons at birth, some possible effects could be masked by such differences. In utero hormonal exposures may be related to the risk of testicular cancer. The protective effects in melanoma may be due to socioeconomic factors.

Adolescent↗
PubMed2002

Familial breast carcinoma risks by morphology: a nationwide epidemiologic study from Sweden.

BACKGROUND: Familial risks in patients with breast carcinoma have not been assessed by morphologic types of medically verified cancers. Reliable data on familial risks would help to establish prevention programs and guide clinical decisions. METHODS: We used the nationwide Swedish Family-Cancer Database to calculate standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for invasive and in situ breast carcinomas in women with mothers and sisters. This database has information on 10.2 million individuals and on more than 13,000 morphology-specific breast carcinomas. RESULTS: SIRs for all invasive breast carcinomas were 1.82 (95% CI 1.71-1.93) for breast carcinoma in the mother and 1.89 (1.70-2.01) for breast carcinoma in a sister. The respective risks were 1.81 and 1.85 for a mother and sisters with ductal breast carcinoma. The SIRs were equally for lobular, tubuloductal, comedo, and mucinous breast carcinomas. However, the SIRs for lobular carcinoma were lower than those for the ductal type, whereas the opposite trend was noted for the comedo and mucinous type; none of the differences were significant. The risks for all morphologic types were highest when both a mother and a sister were affected, SIR 3.19 (2.36-4.22). The risks for in situ breast carcinomas were 2.09 (1.78-2.44) for an affected mother, 2.24 (1.88-2.85) for an affected sister, and 5.23 (2.59-9.39) when both a mother and a sister were affected. CONCLUSIONS: The data suggest that the familial risk of breast carcinoma is independent of the morphologic type. The higher risks in in situ cancer may be due to medical surveillance. The risks were identical from a mother or sister proband, suggesting that recessive effects are unlikely as a heritable cause of breast carcinoma.

Adult↗
PubMed2002

Cancer risks in first-generation immigrants to Sweden.

We used the nationwide Swedish Family-Cancer Database to analyse cancer risks in 613,000 adult immigrants to Sweden. All the immigrants had become parents in Sweden and their median age at immigration was 24 years for men and 22 years for women. We calculated standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for 18 cancer sites using native Swedes as a reference. Data were also available from compatriot marriages. All cancer was decreased by 5% and 8% for immigrant men and women, respectively. However, most of the male increase was due to lung cancer for which male immigrants showed a 41% excess. Among individual cancer sites and immigrant countries, 110 comparisons were significant, 62 showing protection and 48 an increased risk. Most of the differences between the rates in immigrants and Swedes could be ascribed to the variation of cancer incidence in the indigenous populations. Some high immigrant SIRs were 5.05 (n = 6, 95% CI 1.82-11.06) for stomach cancer in Rumanian women and 2.41 (41, 1.73-3.27) for lung cancer in Dutch men. At some sites, such as testis, prostate, skin (melanoma), kidney, cervix and nervous system, the SIRs for immigrants were decreased; in some groups of immigrants SIRs were about 0.20. The highest rates for testicular cancer were noted for Danes and Chileans. Women from Yugoslavia and Turkey had an excess of thyroid tumours. All immigrant groups showed breast, endometrial and ovarian cancers at or below the Swedish level but the differences were no more than 2-fold.

Adult↗
PubMed2002

Cancer risks in second-generation immigrants to Sweden.

We used the nationwide Swedish Family-Cancer Database to analyze cancer risks in Sweden-born descendants of immigrants from European and North American countries. Our study included close to 600,000 0-66-year-old descendants of an immigrant father or mother. We calculated standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for 17 cancer sites using native Swedes as a reference. All cancer was marginally below the Swedish incidence in offspring of immigrant origin. Decreased SIRs were observed for breast cancer among Norwegian descendants, melanoma among descendants of Hungarian fathers and ovarian and bladder cancer among descendents of Finnish mothers, all consistent with the difference in cancer incidence between Swedes and the indigenous populations. Cervical cancer was increased in daughters of Danish men, whereas thyroid cancer and non-Hodgkin's lymphoma were in excess in offspring of parents of Yugoslav and Asian descent. Even these results agreed with the high incidence rates in parents compared to Swedes, except that for non-Hodgkin's lymphoma other explanations are needed; these may be related to immune malfunction. Comparison of the results between the first- and the second-generation immigrants suggest that the first 2 decades of life are important in setting the pattern for cancer development in subsequent life. Birth in Sweden sets the Swedish pattern for cancer incidence, irrespective of the nationality of descent, while entering Sweden in the 20s is already too late to influence the environmentally imprinted program for the cancer destiny.

Adolescent↗
PubMed2002

Environmental and heritable causes of cancer among 9.6 million individuals in the Swedish Family-Cancer Database.

The genetic and environmental components in 15 common cancers were estimated using the nationwide Swedish Family-Cancer Database. Tetrachoric correlations were used to describe similarity in cancer liability among family members. Structural equation modeling was used to derive estimates of the importance of genetic and environmental effects. Statistically significant estimates of proportion of cancer susceptibility, accounted for by genetic effects, were obtained for all studied cancers except for leukemia. The estimate was highest in thyroid cancer (53%), followed by tumors at endocrine glands (28%), testis (25%), breast (25%), cervix (22%), melanoma (21%), colon (13%), nervous system (12%), rectum (12%), non-Hodgkin lymphoma (10%), lung (8%), kidney (8%), urinary bladder (7%), stomach (1%) and leukemia (1%). The estimates of shared environmental effects ranged from 0% (cervix) to 15% (stomach). The childhood shared environmental effects were most important in testicular cancer (17%), stomach cancer (13%) and cervix in situ (13%). Our results indicate that environment has a principal causative role in cancer at all studied sites except for thyroid. The relatively large effect of heritability in cancer at some sites, on the other hand, indicates that even though susceptibility genes have been described at many cancer sites, they are likely to explain only part of the genetic effects.

Breast Neoplasms↗
PubMed2002

Cancer risks in childhood and adolescence among the offspring of immigrants to Sweden.

We used the nation-wide Swedish Family-Cancer Database to analyse the risk of nervous system tumours, leukaemia and non-Hodgkin's lymphoma in age groups 0-4 and 0-19 years among Swedish-born offspring of immigrants. The study included 850 000 individuals with an immigrant background, including European, Asian and American parents. We calculated standardised incidence ratios for the above three malignancies using Swedish offspring as a reference. Subjects were grouped by region or by selected countries of parental origin. No group differed significantly from Swedes in the occurrence of nervous system neoplasm or leukaemia. Offspring of Yugoslav fathers (SIR 2.27) and Turkish parents were at increased risk of non-Hodgkin's lymphoma. The highest risk was noted for non-Hodgkin's lymphoma among young offspring (0-4 years) of two Turkish parents (6.87). The currently available limited data on rates for childhood non-Hodgkin's lymphoma in these countries do not explain the risk in the offspring of immigrants. Yugoslavs and Turks are recent immigrant groups to Sweden, and their offspring have been subject to much population mixing, perhaps leading to recurring infections and immunological stimulation, which may contribute to their excess of lymphomas.

Adolescent↗
PubMed2002

Morphological types of breast cancer in family members and multiple primary tumours: is morphology genetically determined?

BACKGROUND: We conducted the present study to determine whether breast cancer morphology is genetically determined. METHODS: Using the nationwide Swedish Family Cancer Database, which includes data on 10.2 million individuals and over 25,000 morphology-specific breast cancers, we followed morphological types in familial cancers between mothers and daughters and between sisters. Additionally, we recorded morphological data in women who presented with two primary breast cancers and in those who presented with an invasive and in situ breast cancer. We used kappa statistics to examine the association between genetics and morphology. A kappa value of 0 indicates that the process is random and a value of 1 indicates that it is completely determined (i.e. genetic); values between 0.40 and 0.60 are considered to indicate a moderately determined process. RESULTS: The study sample included a total of 25,730 first and 3394 second invasive breast cancers, and 2990 in situ breast cancers. Ductal, lobular, tubuloductal and comedo were the most common invasive types. We identified 164 mother-daughter pairs with breast cancer of a defined morphology, yielding a low kappa value of 0.08. Among 100 sister pairs the kappa value was 0.002. In individuals with two primary breast cancers the kappa values were 0.22 and 0.01 for two invasive and in situ-invasive pairs, respectively. However, for a tumour with a subsequent tumour detected in the contralateral breast less than 1 year later the kappa value was 0.47. CONCLUSION: The data suggest that breast cancer morphology is not genetically determined. However, because of mixed morphologies and the overwhelming prevalence of ductal morphology, the results for rare morphologies should be interpreted with caution.

Adenocarcinoma, Mucinous↗