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Kari Hemminki

Publications and source records attributed to Kari Hemminki.

At least 91 records · Page 5Linked to original sources
PubMed2005

Occupational risk factors for kidney cancer: a cohort study in Sweden.

Although many studies have examined the associations between occupational exposures and kidney cancer, the evidence is not consistent. To examine the risk of occupational exposures on kidney cancer, we carried out a follow-up study on the economically active Swedish population, based on the latest update of the Swedish Family-Cancer Database. We calculated standardized incidence ratios (SIR) and 95% confidence intervals (CIs) for different occupational groups, adjusted for age, period, and socioeconomic status. The reference group was all the economically active population. An increased risk of renal parenchymal cancer was observed for miners and quarry workers, drivers, sales agents, transport workers, and public safety and protection workers among men, and launderers and dry cleaners among women. Significantly increased SIRs of renal pelvical cancer were also observed for the food manufacture workers among men, and journalists and shoe and leather industry workers among women. Male forestry workers, smelters, and metal foundry workers had increased risk for unspecified kidney cancer. Although smoking may explain some of these results, exposure to gasoline, diesel, their exposure products, some metal and chemicals in shoe and leather works, and dry-cleaning products may be associated with kidney cancer.

Confidence Intervals↗
PubMed2005

Familial risk of cancer shortly after diagnosis of the first familial tumor.

BACKGROUND: The diagnosis of the first cancer in a family may lead to the medical examination of the patient's relatives and the subsequent identification of additional familial cancers. If detection bias is present, familial risks could be overestimated soon after first diagnosis. METHODS: We followed 1,677,722 offspring/siblings of 846,448 probands from the year of diagnosis of the first familial tumor to the diagnosis of first cancer, death, emigration, or December 31, 2002, using the Swedish Family Cancer Database. The risks of cancer among the offspring and siblings of patients with melanoma and cancers of the breast, prostate, colorectum, cervix, and lung were compared with those in the general population. Relative risks (RRs) were determined using Poisson regression, according to the time after first diagnosis. All statistical tests were two-sided. RESULTS: Daughters of women with breast cancer had a statistically significantly higher relative risk of in situ breast cancer during the year of the mother's diagnosis than they did 5 or more years later (RR = 4.78, 95% confidence interval [CI] = 2.16 to 10.6, 26.6 cases per 100,000, versus RR = 1.97, 95% CI = 1.65 to 2.37, 27.2 cases per 100,000; P = .033). Daughters diagnosed the same year as their mothers were younger and were diagnosed earlier in the calendar year than daughters of women diagnosed 5 or more years after their mothers. Similarly, the risk of invasive melanoma among the offspring of individuals with invasive melanoma was higher during the year of the parent's diagnosis than it was 5 or more years afterward (RR = 8.27, 95% CI = 3.82 to 17.9, 57.0 cases per 100,000, versus RR = 3.18, 95% CI = 2.55 to 3.97, 37.6 cases per 100,000; P = .019). Sibling risks of in situ breast cancer, in situ cervical cancer, and invasive prostate cancer also decreased with time after diagnosis of the first familial tumor. CONCLUSIONS: Increased surveillance may result in the earlier detection of asymptomatic familial cancers, i.e., in detection bias. The possibility of overestimated familial risks of cancer shortly after diagnosis of the first familial tumor should be considered before a patient's clinical and genetic counseling is implemented.

Adult Children↗
PubMed2005

Association of the CASP10 V410I variant with reduced familial breast cancer risk and interaction with the CASP8 D302H variant.

Dysregulation of apoptosis plays a crucial role in carcinogenesis. As part of death receptor- and mitochondrion-mediated apoptosis, the homologues caspases 10 and 8 may act as low-penetrance breast cancer (BC) susceptibility genes. In death receptor-mediated apoptosis, engagement of death receptors by their ligands involves the assembly of the death-inducing signalling complex (DISC). In mitochondrion-mediated apoptosis, the release of cytochrome c into the cytosol results in apoptosome formation. Recruitment of both caspases 10 and 8 (CASP10 and CASP8, respectively) to DISC and apoptosome leads to their activation by dimerization. We investigated the influence of the coding CASP10 variant V410I (G1228A) by performing a case-control study - using 511 familial BC cases and 547 control subjects - on BC risk and revealed a significant association of V410I with a reduced risk (OR = 0.62, 95% CI = 0.43-0.88, P = 0.0076) related to the number of variant alleles (P(trend) = 0.0039). As CASP10 and CASP8 functionally co-operate during apoptosis, we analysed the mutual effect of both CASP10 V410I and CASP8 D302H, resulting in a significant association between the number of the variant alleles I410 and H302 and a highly decreased familial BC risk (OR = 0.35, P(trend) = 0.007), pointing to the interaction between the CASP10 and CASP8 polymorphisms in breast carcinogenesis.

Adult↗
PubMed2005

Socioeconomic/occupational risk factors for lymphoproliferative diseases in Sweden.

PURPOSE: The aim of the study is to investigate associations between socioeconomic and occupational factors and lymphoproliferative (LP) diseases. METHODS: We performed a follow-up study on the economically active Swedish population, based on the Swedish Family-Cancer Database. Standardized incidence ratios and 95% confidence intervals were calculated in different social classes and occupations. RESULTS: An increased risk for LP diseases was observed for physicians, plumbers, chemical process workers, and food manufacture workers among men and shoe and leather workers, mechanics, iron and metalware workers, and launderers and dry cleaners among women. CONCLUSIONS: Results suggest that socioeconomic and occupational factors have a minor effect on risk for LP diseases. Exposure to organic solvents may increase the risk for some LP diseases, although inconsistencies of findings between subcohorts do not rule out spurious associations.

Female↗
PubMed2005

Effects of screening for breast cancer on its age-incidence relationships and familial risk.

Mammographic screening programs for breast cancer have been implemented in many countries and opportunistic mammographies are taken as a diagnostic method. The consequences of the wide application of this technology to age-incidence relationships in breast cancer have not been clarified nor is its effect on familial risk estimation. It was assumed that if screening and diagnostic methods bias familial risk, the highest risk should be noted for sisters diagnosed close in time. Age-specific incidence data were collected from the EUCAN database and from cancer registries of Finland, Norway and Sweden. The Swedish Family-Cancer Database was used to analyse risks for breast cancer among sisters, depending on the time since the first sister was diagnosed with breast cancer. Age-incidence patterns deviated between Germany, with low mammographic coverage, and Sweden, the Netherlands, the UK and France, with variable levels of coverage. The annual age-incidence patterns in Finland, Norway and Sweden changed in concert with the targeted mammographic service. The risk of breast cancer for women with an affected sister, diagnosed between ages 50 to 64 years, was significantly higher within the same or the subsequent year of the sister's diagnosis compared to 5+ years, accounting for 7.3% of all patients. The ordered increase in age-specific incidence of breast cancer in the women targeted by screening studied suggests that mammographic screening is one important factor responsible for the shift of the age of onset for breast cancer towards middle age. However, the effects on the estimation of familial risk are so far small.

Adult↗
PubMed2005

Familial risks for migraine and other headaches among siblings based on hospitalizations in Sweden.

Migraine and other headaches are common disabling conditions, reducing the quality of life in the affected individuals. The unambiguous definition of familial risk for subtypes of migraine and other headaches will advance the search for the heritable causes of these conditions and their underlying mechanisms. We aim at defining familial risks for siblings to be hospitalized because of migraine or other headaches. An ad hoc migraine database was constructed by linking the Multigeneration Register on 0- to 69-year-old siblings to the Hospital Discharge Register for data on migraines of all hospitalized patients in Sweden from years 1987 to 2001. Standardized incidence ratios (SIRs) were calculated for affected sibling pairs by comparison with those whose siblings had no migraine. Among a total of 14,123 hospitalized patients, 205 affected siblings were identified, with a familial SIR of 2.84. SIRs for migraine with and without aura were 3.08 and 2.67, respectively. The highest familial risk of 3.71 was noted for unspecified migraine. The risk tended to be higher for concordant (both siblings sharing the migraine subtype, ranging from 4.0 to 6.0) than discordant subtypes, but even many discordant SIRs were significant. The SIR for spouse correlation was 1.14 for husbands and 1.22 for wives, far from being significant. All subtypes of hospitalized migraines and other headaches show an increased familial risk, at least in specific age groups. The different subtypes appear to share susceptibility, which may imply common disease mechanisms.

Adolescent↗
PubMed2005

Association of genetic variants in the Rho guanine nucleotide exchange factor AKAP13 with familial breast cancer.

The A-kinase anchor protein 13 (AKAP13, alias BRX and lbc) tethers cAMP-dependent protein kinase to its subcellular environment and catalyses Rho GTPases activity as a guanine nucleotide exchange factor. The crucial role of members of the Rho family of GTPases in carcinogenesis is well established and targeting Rho proteins with antineoplastic compounds has become a major effort in the fight against cancer. Thus, genetic alterations within the candidate cancer susceptibility gene AKAP13 would be expected to provoke a constitutive Rho signalling, thereby facilitating the development of cancer. Here, we analysed the potential impact of four polymorphic non-conservative amino acid exchanges (Arg494Trp, Lys526Gln, Asn1086Asp and Gly2461Ser) in AKAP13 on familial breast cancer. We performed a case-control study using genomic DNA of BRCA1/2 mutation-negative German female index patients from 601 unrelated families, among a subset of 356 high-risk families, and 1053 German female unrelated controls. The newfound Lys526Gln polymorphism revealed a significant association with familial breast cancer (OR = 1.58, 95% CI = 1.07-2.35) and an even stronger association with high-risk familial breast cancer (OR = 1.85, 95% CI = 1.19-2.88). Haplotype analyses were in line with genotype results displaying a similar significance as analyses of individual polymorphisms. Due to the pivotal role of AKAP13 in the Rho GTPases signalling network, this variant might affect the susceptibility to other cancers as well.

A Kinase Anchor Proteins↗
PubMed2005

Variation in the risk for liver and gallbladder cancers in socioeconomic and occupational groups in Sweden with etiological implications.

OBJECTIVES: To examine the associations between socioeconomic/occupational factors and liver cancer at various anatomic sites (including primary liver, gallbladder and other cancers). METHODS: We carried out a follow-up study on the economically active Swedish population, based on the Swedish Family-Cancer Database. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated in different social classes and occupations. RESULTS: For primary liver cancer, farmers were at a decreased risk; increased risks were observed for male sales agents, journalists, seamen, waiters, cooks and female beverage manufacture workers. Similar patterns were observed for gallbladder cancer; workers employed as journalists, sales agents, cooks and stewards, and public safety workers showed increased risk. Only male transport workers showed increased risk of cancers in other parts. CONCLUSIONS: Occupations with high consumption of alcohol and/or high prevalence of smoking associated with a risk of liver and gallbladder cancers. The present study suggests that the effects of socioeconomic factors on liver cancer of different subsites are similar; alcohol drinking is a risk factor of gallbladder cancer because of the covariation of primary liver and gallbladder cancers in occupational groups.

Adult↗
PubMed2005

Familial association of prostate cancer with other cancers in the Swedish Family-Cancer Database.

BACKGROUND: Familial associations between cancer sites may implicate true familial clustering which is relevant for the identification of new cancer syndromes and for clinical counseling. METHODS: We used the nation-wide Swedish Family-Cancer Database, containing 10,553 sons and 107,518 fathers with prostate cancer among a total of 170,000 cancer patients in the 0- to 70-year-old offspring generation and over 800,000 cancer patients in the parental generation. We calculated familial standardized incidence ratios (SIRs) and confidence intervals (CIs) for prostate cancers and other cancers in family members. RESULTS: SIRs for prostate cancer were increased in sons when mothers were diagnosed with breast and ovarian cancers, and when siblings were diagnosed with Hodgkins disease (1.78, N = 18, 95% CI 1.05-2.82) and leukemia (1.39, 43, 1.01-1.88). Liver cancer and melanoma were also in excess in the high-risk families. CONCLUSIONS: The present analysis, the largest yet carried out, found many novel associations implying familial links between prostate cancer and other sites.

Adolescent↗
PubMed2005

Genetic polymorphisms and possible gene-gene interactions in metabolic and DNA repair genes: effects on DNA damage.

We investigated in a central European population, the association between genetic polymorphisms in several genes coding for xenobiotic metabolizing enzymes (CYP1A1, CYP2E1, EPHX1, GSTP1, GSTM1 and GSTT1) and in DNA repair genes (XPD, XPG, XPC and XRCC1) and the levels of single-strand breaks (SSBs) and SSB endonuclease III sensitive sites (endoIII sites) in peripheral blood lymphocytes. No significant differences in the mean levels of SSBs and endoIII sites after stratification for main confounders and occupational exposure were observed in the studied population. Significantly higher levels of SSBs were observed in individuals bearing the wild-type alleles (AA) (0.75+/-0.51SSB/10(9)Da) and heterozygous (AC) genotypes (0.67+/-0.49SSB/10(9)Da) compared to those with homozygous XPD (CC) genotype (0.43+/-0.28SSB/10(9)Da, P=0.033). A moderate increase in the levels of SSBs was also found in individuals with the homozygous XPG exon 15 wild type (GG) and heterozygous (GC) genotypes in comparison to those with the homozygous (CC) genotype (P=0.066) and in individuals with low activity EPHX1 genotype in comparison to those with high activity genotype. Nevertheless, these differences were not statistically significant. No other significant association was found. When gene-gene interactions were evaluated, a combination of EPHX1 activity genotypes with that of either XPD or XPG significantly (P=0.003 and 0.016, respectively) modulated SSB levels resulting in a three-fold difference between the "protective" and the "adverse" genotype-combinations. Almost three-fold differences in SSB levels were found between the "protective" and the "adverse" genotype-combinations of EPHX1 activity genotype and GSTM1 or GSTT1 genotypes, respectively. In conclusion, our results suggest a relation between markers of genotoxicity and polymorphisms in genes coding for xenobiotic metabolizing and DNA repair enzymes as well as a modulating effect of combinations of these polymorphisms.

Adult↗
PubMed2005

Low frequency of BRAF and CDKN2A mutations in endometrial cancer.

Several pathways have been implicated in the pathogenesis of endometrial carcinoma. Based on recent reports, BRAF mutations provide an alternative route for activation of the RAS signalling pathway. The CDKN2A (p16) tumour suppressor gene is also altered in several tumour types. We therefore wanted to assess the pattern and prognostic impact of BRAF mutations and p16 alterations in endometrial carcinomas. Only 1 of 48 tumours (2%) was found to have a BRAF mutation in exon 15, whereas 8 of 45 tumours (18%) had a K-ras mutation. Homozygous deletion, amplification, promoter region methylation or mutation of the p16 gene was seen in 6 cases (13%), and 18 cases (38%) carried polymorphisms in the p16 gene. All tumours with presence of p16 methylation, non-sense mutation, deletion or amplification exhibited loss of p16 expression as evaluated by immunohistochemistry. Presence of a p16 hit was significantly correlated with high FIGO stage (p = 0.04), high histologic grade (p = 0.02), estrogen receptor negativity (p = 0.05), pathologic expression of p53 (p = 0.02), pathologic expression of p16 (p = 0.05) and poor survival (p = 0.02). There was also a significant correlation between loss of p16 expression and K-ras mutations, pathologic p53 expression and serous papillary/clear cell histologic types (p = 0.05/p = 0.001/p = 0.002). In conclusion, BRAF mutation is an infrequent finding in endometrial carcinomas. Loss of p16 expression is seen in all cases with alterations of the p16 gene. The presence of a p16 hit might be important in a subset of endometrial carcinomas with aggressive clinical behaviour. However, the mechanism of p16 inactivation remains unclear for the majority of cases exhibiting loss of expression, but the interactions with K-ras and p53 should be further studied.

Aged↗
PubMed2005

Familial risks for nonmedullary thyroid cancer.

CONTEXT: Reliable data on familial risks are important for clinical counseling and cancer genetics. OBJECTIVE: We wanted to define familial risks for histopathology-specific nonmedullary thyroid cancers through parental and sibling probands. SETTING: The study examines the nationwide Swedish Family-Cancer Database on 10.5 million individuals, containing families with parents and offspring. PATIENTS: Cancer data were retrieved from the Swedish Cancer Registry from years 1958 to 2002, including 3292 patients with thyroid adenocarcinoma. The Systematized Nomenclature of Medicine histology was available from 1993 onward, with 1449 papillary, 288 follicular, 148 anaplastic, and 68 Hurthle cell tumors. MAIN OUTCOME MEASURES: Familial risk for offspring was defined through standardized incidence ratio, adjusted for many variables. RESULTS: The familial risk for papillary carcinoma was 3.21 and 6.24 when a parent and a sibling, respectively, were diagnosed with thyroid cancers. There was an apparent gender preference, particularly among sisters, whose risk was 11.19. The risks were highest for early onset cancers. Thyroid adenocarcinoma was shown to be associated with melanoma and connective tissue tumors, and probably also with neurinomas (schwannomas). Associations found in single comparisons with papillary thyroid cancer and other sites included right-sided colon, breast, ovarian, and kidney cancers. Hurthle cell tumors were associated with Hodgkin's and non-Hodgkin's lymphoma, but the numbers of cases were small. CONCLUSIONS: The present findings were based on a limited number of cases, but they display a complex and heterogeneous pattern of familial nonmedullary thyroid cancer. The high risk for papillary carcinoma among women requires clinical attention, although the absolute risks for this rare cancer are still low.

Adenocarcinoma↗
PubMed2005

Familial risks for colorectal cancer show evidence on recessive inheritance.

Recent molecular genetic data have become available on a recessive inheritance in colorectal cancer (CRC). We wanted to search for evidence for recessive inheritance from a population-based family data set, which is not sensitive to reporting or ascertainment bias. The nationwide Swedish Family-Cancer Database covered 10.3 million individuals whose invasive CRCs of adenocarcinoma histology were followed from 1991 to 2000. Age of the offspring and parental populations was limited to less than 69 years. Standardized incidence ratios (SIRs) were calculated for site-specific CRC in offspring whose parents or siblings were diagnosed with CRC. A total of 6,774 offspring were recorded with CRC, whose risk was 2.13 when a parent was diagnosed with CRC and it was 2.75 when a sibling was affected. The SIRs for right-sided colon cancer were 7.53 among siblings and 3.66 among offspring of affected parents, giving a 1.8-fold excess familial risk among siblings. Colon cancer among the 0- to 68-year-old population accounted for about 25% of all colon cancers. Examination of all cancers in family members of the affected siblings did not reveal large contribution by known syndromes, such as hereditary nonpolyposis colorectal cancer. The most likely explanation to the high risk of right-sided colon cancer among siblings is a recessive inheritance, which would account for 0.75% of all CRCs. Its high prevalence and predilection to right-sided colon suggest that only a small proportion of this familial aggregation could be due to MYH mutations.

Adolescent↗
PubMed2005

Relationships between familial risks of cancer and the effects of heritable genes and their SNP variants.

Familial risks for cancer can be used in many ways in guiding gene identification efforts and, more broadly, in understanding cancer etiology. Gene identification efforts may be properly designed and targeted if the familial risks are well characterized and the mode of inheritance is identified. Single nucleotide polymorphisms (SNPs) are extensively used in case-control studies of practically all cancer types. They are used for the identification of inherited cancer susceptibility genes and those that may interact with environmental factors. However, being genetic markers, they are applicable only on heritable conditions, which is often a neglected fact. Based on the data in the nationwide Swedish Family-Cancer Database, we review familial risks for all main cancers and discuss the evidence for a heritable component in cancer. The available evidence, including differences in cancer incidence between regions and temporal changes within regions, indicates that cancer is mainly an environmental disease, with a minor heritable etiology. The large environmental component will hamper the success of SNP-based genetic association studies. Empirical familial risks should be used to evaluate the feasibility of such studies. We develop figures for the assessment of genetic parameters based on familial risks. Such data are helpful in the estimation of the expected genetic effects in cancer. Overall, we consider the likelihood of a successful application of SNPs in gene-environment studies small, unless established environmental risk factors are tested on proven candidate genes.

Environment↗
PubMed2005

Association of death receptor 4 haplotype 626C-683C with an increased breast cancer risk.

Dysregulation of apoptosis plays a crucial role in carcinogenesis. Tumour necrosis factor-related apoptosis-inducing ligand stimulates the extrinsic apoptotic pathway by binding to death receptor 4 (DR4). Thus, genetic alterations within the candidate tumour suppressor gene DR4 would be expected to provoke a deficient apoptotic signalling thereby facilitating the development of cancer. The DR4 variants Thr209Arg and Glu228Ala were genotyped in a series of 521 breast cancer cases and 1100 control subjects from Germany, determining their impact on breast cancer risk. Neither Thr209Arg (626C>G) nor Glu228Ala (683A>C) alone were significantly associated with breast cancer risk [odds ratio (OR) = 0.84, 95% confidence interval (CI) = 0.65-1.08, P = 0.18 and OR = 0.89, 95% CI = 0.72-1.12, P = 0.30]. However, haplotype analysis revealed a 3.5-fold risk for carriers of the 626C-683C haplotype (OR = 3.52, 95% CI = 1.45-8.52, P = 0.003).

Adult↗