Search

Temperature control of food products in retail food stores (food stores) is essential for food safety. The food business operator (FBO) must ensure that the product temperatures comply with food regulations. This study investigated the temperatures of products in 32 food stores and the relationship between the product temperature with the temperature of the refrigeration equipment (open front) and the temperature settings. The FBOs awareness of the equipment and product temperatures and the equipment temperature settings (temperature setpoint, alarm setpoint, timing for alarm to go off) were also investigated. The food stores represented four nationwide chain-store groups in Finland. The study included four categories of food products namely: fresh fish, minced meat, vacuum packed ready-to-eat processed fish and other ready-to-eat products, all of which are easily perishable products. Vacuum packed fish products and other ready-to-eat products are also sensitive to Listeria monocytogenes contamination. The temperatures of the products (n = 84) and refrigeration equipment (n = 86) were measured by a temperature data logger by the health inspector for 24 h. Temperature violations were observed in 50% of the products and 17.9% of the products exceeded the temperature limit by over 3 °C for more than 30 min. Products that were most often in noncompliance were fresh fish and vacuum packed processed fish products. Temperature violations were observed in food stores in all four chain-store groups and no significant difference between the chain-store groups was observed. The temperature of the equipment as measured by the refrigeration equipment's fixed thermometers differed significantly from the temperatures of the products. Moreover, no significant correlation was found between the equipment temperatures (fixed thermometer) and the products with the exception of minced meat. These results highlight, that the product temperature could not be reliably determined by the equipment's fixed thermometer. There was a lack of awareness of temperature settings in all chain-store groups. Only three stores (9.4%) were aware of all the settings of the inspected equipment. The results show that the FBOs own-check of equipment and product temperatures is not functioning correctly in food stores. This can have serious consequences for food safety. FBOs, equipment manufacturers, monitoring system providers and official food control authorities should take active measures to improve the situation.

Official food control inspects retail food stores (food stores) regularly for compliance with food safety regulations. The health officer (inspector) inspects the food store's own-check (self-verification) and facilities and operations. The own-check inspection is usually performed on-site and includes the examination of own-check documentation. The chain-store groups (grocery multiple retailers) studied have developed an internet based own-check databank for documentation of own-check data for their own use, and also to enable official food control to make inspections via the internet. The chain-stores aim to speed up and possibly decrease the number of on-site inspections made by the official control in food stores. The purpose of this study was to investigate the accuracy and reliability of the own-check databank from the view of official food control. Fourteen food stores that represented three different national chain-store groups in a local municipality in Finland were included in the study. The own-check documentation from a 3-month period with regard to the receiving of products, cleanliness and temperatures of the refrigeration equipment was inspected by the official control via the internet based own-check databank. This was followed by an on-site inspection for comparison. The frequency of non-compliance for cleanliness recorded by the inspector on-site was significantly higher than the frequency of non-compliance recorded in the databank (Fisher's exact test, p 3 °C for at least 30 min) of refrigeration equipment for minced meat and processed fish products, determined by temperature data logger (24 h measurement), in 57.1% (8/14) of the stores. In contrast, no non-compliance regarding those same refrigeration equipment was recorded in the databank during a 3-month period. Discrepancies between the inspection results of cold holding and cleanliness in the databank and the on-site inspections were observed in food stores representing all three chain-store groups. The observed differences between the databank data and the on-site inspections, suggest that the frequency of on-site inspections should not be decreased or substituted by off-site databank inspections. Issues of on-site inspection and off-site databank inspection are discussed. Further, the study revealed serious problems in maintaining and monitoring of the temperature in refrigeration equipment in food stores.

We aimed to estimate the 15-year and lifetime risks of contralateral breast cancer in breast cancer patients according to the age of diagnosis of the first cancer and the history of breast cancer in the mother. The risks of contralateral breast cancer were estimated for all 78,775 breast cancer patients in the Swedish Family-Cancer Database (age at diagnosis of first breast cancer70 years). The risk of experiencing a contralateral breast cancer within 15 years of diagnosis was 8.4% [95% confidence interval (CI): 8.1-8.7%] for women with an unaffected mother, was 12% (95%CI: 11-13%) for a woman with a mother with unilateral breast cancer and was 13% (95%CI: 9.5-17%) for women with a mother with bilateral breast cancer. In early-onset diagnosed women (50 years) with an unaffected mother, the risk of contralateral breast cancer until age 80 was 23% (95%CI: 20-26%) and for late-onset (50-69 years) diagnosed women it was 17% (95%CI: 14-21%). In a woman with a mother with an early-onset unilateral breast cancer, risk of contralateral breast cancer by age 80 was 35% (95%CI: 25-46%). Women with a mother with early-onset bilateral breast cancer had 31% (95%CI: 12-67%) lifetime risk of contralateral breast cancer. The risk of contralateral breast cancer is higher for daughters of breast cancer patients than for daughters of women without breast cancer. Maternal cancer history and age at onset of first breast cancer in women should be taken into account when counseling breast cancer patients about their risk of contralateral breast cancer.

We use data on lymphoma in families of Hodgkin lymphoma (HL) cases from the Swedish Family Cancer Database (Hemminki et al. 2001) to illustrate survival methods for detecting familial aggregation in first degree relatives of case probands compared to first degree relatives of control probands, from registries that permit sampling of all cases. Because more than one case may occur in a given family, the first degree relatives of case probands are not necessarily independent, and we present procedures that allow for such dependence. A bootstrap procedure also accommodates matching of case and control probands by resampling the matching clusters, defined as the combined set of all first degree relatives of the matched case and control probands. Regarding families as independent sampling units leads to inferences based on "sandwich variance estimators" and accounts for dependencies from having more than one proband in a family, but not for matching. We compare these methods in analysis of familial aggregation of HL and also present simulations to compare survival analyses with analyses of binary outcome data.

We used the nation-wide Swedish Family-Cancer Database to analyse cancer risks in men who had had children with more than one woman. Cancer cases were retrieved from the Swedish Cancer Registry from years 1961-1998. A total of 2.9 million men and 298,134 cancer cases were covered. For men having children with two, three or more women, increasing risk trends were shown for upper aerodigestive tract, lung, urinary bladder and oesophageal cancers. Decreasing trends were observed for tumours of the colon, skin (squamous cell and melanoma), nervous system and endocrine glands and against myeloma and non-Hodgkin's lymphoma. The present results indicated that men who had had children with multiple women showed an excess of smoking- and alcohol consumption-related cancers. The decreased risks for colon cancer, non-Hodgkin's lymphoma and melanoma were possibly related to lifestyle factors connected with economic deprivation, less obesity and physical fitness. These ill-defined protected factors may be a challenge to epidemiological studies.

We used the nationwide Swedish Family-Cancer Database to analyse cancer risks in women who have had children with different men. Cancer cases were retrieved from the Swedish Cancer Registry for 1961-1998. A total of 3 million women and 316 497 cancer cases were covered. For women having children with more than one partner, an increased risk was shown for upper aerodigestive tract, anal, liver, pancreatic, lung, cervical, other female genital, kidney and urinary bladder cancers. A decreased risk was observed for breast and endometrial cancer, and melanoma. In women who had at least three or more children with three or more partners, the increased risks were even more pronounced for pancreatic, lung and cervical cancer. Conversely, the risk for breast and endometrial cancer, and melanoma was decreased. The present results indicated that women who had children with multiple partners showed an excess of smoking-related and sexually transmitted cancers. The decreased risks for breast and endometrial cancer and for melanoma were possibly related to lifestyle factors connected with economic deprivation. The magnitude of the effects was so large that failure to consider the number of partners may introduce bias.

Summary Over 250 individuals fell ill in five outbreaks caused by Cryptosporidium parvum in Finland, October–November 2012. The cases were connected by lunch meals at restaurants in four different cities. In two outbreaks, the same C. parvumIIdA17G1 subtype was found in patients’ stool samples which supports a single source of infection. Frisee salad was the only common food item served at the restaurants, and consumption of lunch salad containing the frisee salad was associated with the illness. Lunch customers who responded that they had eaten lunch salad were three times more likely to have become ill than those who had not answered whether they had eaten the salad or not (RR 2.66; 95% Cl 1.02–6.9, P-value

SUMMARYIn 2010, 7/44 (16%) reported foodborne outbreaks in Finland were linked with raw beetroot consumption. We reviewed data from the national outbreak registry in order to hypothesize the aetiology of illness and to prevent further outbreaks. In the seven outbreaks, 124 cases among 623 respondents were identified. Consumption of raw beetroot was strongly associated with gastrointestinal illness (relative risk 8·99, 95% confidence interval 6·06–13·35). The illness was characterized by sudden onset of gastrointestinal symptoms; the median incubation time was 40 min and duration of illness 5 h. No common foodborne pathogens or toxins were found in either clinical or beetroot samples, but all tested beetroot samples were of poor quality according to total bacterial counts. Beta-haemolytic Pseudomonas fluorescens was detected in several beetroot samples but its effect on human health is unknown. No outbreaks were reported after the Finnish Food Safety Authority Evira advised against serving raw beetroot in institutional canteens.

Carcinogen-DNA adducts and somatic gene mutation at the hypoxanthine guanine phosphoribosyl transferase (HPRT) locus were evaluated in peripheral leukocytes of workers in an iron foundry with exposure to benzo[a]pyrene (B[a]P) and other polycyclic aromatic hydrocarbons (PAHs). During the two year study period, B[a]P exposure declined by approximately 40%, from a maximum of 60 ng/m3 in the first year to < 36 ng/m3 1 year later. A total of 64 persons were sampled in November/December of the two successive study years; 24 of them gave two samples one year apart. The biomarkers included carcinogen-DNA adducts in leukocytes (PAH-DNA measured by an immunoassay, aromatic-DNA by the 32P-postlabeling method) and HPRT mutation in lymphocytes. After adjusting for smoking, levels of PAH-DNA, aromatic-DNA and HPRT mutation frequency (Mf) increased with exposure among the 64 workers sampled during the 2 year period (P < or = 0.05). However, the markers showed a differential response to the change in exposure, consistent with their individual biology. For example, among the 24 workers sampled in both years, carcinogen-DNA adducts (which have a half-life on the order of several months) were markedly reduced from the first to the second year (PAH-DNA, 6.2 versus 2.3/10(8); aromatic-DNA, 2.5 versus 1.4/(8); P < 0.01). HPRT Mf (a longer-lived marker) was somewhat less affected by the decline in exposure (1.3 versus 0.8, P < or = 0.05). Moreover, in the second year several long-term workers had low levels of adducts, but elevated HPRT Mf. Thus, PAH-DNA and HPRT Mf were highly correlated in the first year (n = 17; r = 0.67; P < 0.01), but not in the second year or in the two years combined. However, when analysis was restricted to workers with detectable levels of adducts (who included the more highly exposed workers) the correlation was significant between PAH-DNA and HPRT (n = 17; r = 0.65; P = 0.005). In contrast, aromatic-DNA adducts and HPRT were not correlated in either year. These results suggest a molecular link between somatic gene mutation and PAHs; and they highlight the need in such molecular epidemiologic studies to consider the varying lifetimes of the individual markers.

Increased cancer risk after psoriasis has been observed in previous studies, whereas little is known about the prognosis in cancer patients with previously diagnosed psoriasis.We aimed at examining the cancer-specific and overall mortality among psoriatic cancer patients compared with the reference population.The population-based Swedish registers were used to identify psoriatic cancer patients and cancer patients without psoriasis. We estimated hazard ratios (HRs) showing the probability of death in the two groups.In total, 1746 psoriatic cancer patients and 1 011 757 other cancer patients were identified from 1964 to 2006, showing a significant survival disparity [overall HR 1·27, 95% confidence interval (CI) 1·20-1·35 and cancer-specific HR 1·26, 95% CI 1·18-1·35]. An overall mortality excess after psoriasis was observed for nine cancer sites and a cancer-specific mortality excess for seven cancer sites. Stratified analyses showed that the prognosis was worse for psoriatic cancer patients diagnosed below age 65 years and for those who had been treated for alcohol-related diseases. Those with more than one hospitalization for psoriasis were more likely to be associated with an increased risk of cancer-specific mortality.A previous diagnosis of psoriasis worsens the prognosis of many cancers. A worse prognosis was more pronounced in psoriatic cancer patients diagnosed at an earlier age, previously hospitalized for alcohol-related diseases, or with severe symptoms. Our study provides clinicians and patients with information about mortality risk and prognostic factors for psoriatic cancer patients. The mechanisms underlying this disparity warrant further studies.

A family history of melanoma is associated with an increased risk of melanoma and probably of other, discordant cancers. Limited data are available on familial mortality in melanoma. If fatal forms of melanoma were associated with fatal forms of melanoma or of some other cancers, only studies on familial mortality rather than on familial incidence might be able to detect them. Furthermore, estimates on familial aggregation based on mortality are free from bias of overdiagnosis.The aim of this study was the estimation of familial aggregation of concordant melanoma and of melanoma and any other cancers based both on incidence and on mortality.We used the nationwide Swedish Family-Cancer Database to calculate standardized incidence ratios (SIRs) for incident melanoma for relatives of any cancer patients and standardized mortality ratios (SMRs) for death from melanoma for relatives of individuals who died from any other cancer. Similar risks were determined for any common cancer when relatives were affected by melanoma.For concordant melanoma, familial incidence equalled familial mortality, SIR=SMR. Familial clustering (SIRs increased) of melanoma and oesophageal, colorectal, breast, prostate, kidney, nervous system and connective tissue cancers and myeloma and leukaemia was observed. The SMRs for pancreatic and nervous system cancers were increased in relatives whose parents had died from melanoma.These data should encourage a search for fatal subtypes of familial cancer, which may eventually have clinical implications.

The coding of histology of nervous system (NS) tumors with various degrees of malignancies differs between cancer registries, whereby the comparison of incidence rates from one registry to another seems difficult. No study has systematically defined whether the change in the risk of NS tumors upon immigration in adulthood varies by subsite or histology. Therefore, we aimed to address this issue amongst the first-generation immigrants to Sweden based on a large uniform cancer registry data (1958-2006).The nationwide Swedish Family-Cancer Database (2008 version;11.8 million individuals; 1.8 million immigrants; histology code in force since 1958) was used to calculate standardized incidence ratios (SIRs). We analyzed 28,981 adult cases of NS tumors amongst Swedes and 2519 amongst immigrants (age ≥ 30).Significantly decreased risks for brain glioma were amongst German (SIR = 0.64), Eastern European (0.62), some Asian (0.71), Chilean (0.34), and African immigrants (0.52). We found an increased risk for brain meningioma amongst Finns (1.15) and former Yugoslavians (1.33), whilst only Norwegians (0.71) and Latin Americans (0.21) had a decreased risk. The risk for spinal ependymoma and astrocytoma was increased in Germans (3.66) and former Yugoslavians (8.89). We found no significant difference for peripheral nerve tumors between immigrants and the native Swedes.Significant differences between risk of NS tumors amongst immigrants and the native Swedes may suggest different risk factor profiles for glioma compared to meningioma indicating a higher etiological role of genetic background or childhood environmental risk factors rather than exposures after immigration.

Type 1 diabetes mellitus (T1DM) is an autoimmune disease with potential mechanistic links to immune-related cancers. We aimed at examining the overall and specific cancer risks among hospitalized T1DM patients from the national registers in Sweden.A T1DM research cohort was created by identifying T1DM patients from the Hospital Discharge Register and linking them with the Cancer Registry. Standardized incidence ratios (SIRs) for subsequent cancers were calculated among patients with T1DM compared with those without T1DM.Two hundred and fifty-eight cases were ascertained with subsequent cancers during the follow-up duration from 1964 to 2006, with an increased overall SIR of 1.17 (95% CI 1.04-1.33) among 24 052 T1DM patients identified at baseline. Significant excess was noted for gastric and skin (squamous cell carcinoma) cancers and for leukaemia. Increased risk of acute lymphatic leukaemia accounted for most of the variation of leukaemia risk (SIR = 5.31, 95% CI 3.32-8.05). Cancer risk varied with sex, age at first hospitalization and numbers of hospitalizations. The risk was higher in women compared with men and in those hospitalized for T1DM at age over 10 years compared with the younger patients. Higher risks were also found among those with more hospital visits.By quantifying the variations of overall and site-specific cancer risks after T1DM, the current study provides novel associations between T1DM and subsequent cancers, the mechanisms of which remain to be established.

There is very little research on patient organizations (POs), even though their numbers and influence seem to be increasing. The purpose of this study was to describe the establishment, membership, size, organization, decision making and basic funding of national POs in Finland.National POs (n = 130) were identified from their umbrella organizations and by Internet searches. Data were collected from POs' web pages (87% of POs had one), Finland's Slot Machine Association (RAY, an important public financier of POs), a relevant survey done by a local TV-company, and interviews and written materials of POs.Some current national POs were established around the turn of the 19(th) century. The rate of establishment of new POs increased from the 1970s and particularly in the 1990s when POs were characterized by increasing specialization. POs focused on different patient groups and diseases and were founded by philanthropists, physicians, patients, parents and the drug industry. Members could be patients, patient relatives, health-care professionals and organizations. POs widely varied in memberships (20-145 000, in 2002) and in number of paid personnel (0-1395, in 2002), organizational structure and decision making. Interest groups and financiers were often represented in decision-making organs. Activities included mutual support and service production, and, increasingly, informing and lobbying. POs had wide domestic and international co-operation and networking. Drug industry marketing was visible on PO web pages. Budget sizes varied (4000-15 million euros, in 2001). The main public financier was RAY. The old national POs were large and part of national social and health care, but newer ones were often established for mutual support and lobbying. National POs are not uniform but characterized by great variation. The number of national POs is increasing suggesting tighter competition for financing and visibility in the future.

Several small studies combined have suggested that twins develop fewer childhood cancers than singletons. The national Swedish Family-Cancer Database contains information on a large population of multiple births providing an unbiased dataset for the estimation of cancer risk in twins. Lifelong cancer incidence in these twins has already been reported as similar to that in singleton births. In contrast, the present paper presents robust estimates of a significantly reduced childhood cancer risk in twins to age 15.Standardised incidence ratios (SIR) were used to measure cancer risk for twins, taking the corresponding rates for singletons as reference. Rates were adjusted for age, sex, period of birth, and residential area. Follow up data cover the period 1958-2002.Overall childhood cancer risk was significantly reduced in all twins (SIR 0.81 [95% CI: 0.69-0.94]) as was the risk for Wilms tumour (SIR 0.34 [95% CI: 0.09-0.88]). These significant reductions in risk were both driven by effects in same sex twins (overall cancer SIR 0.77 [95% CI: 0.64-0.93], Wilms tumour 0.12 [95% CI: 0.00-0.71]). Leukaemia risk was also significantly reduced for same sex twins (SIR 0.69 [95% CI: 0.47-0.97]).Our study provides the evidence that twins experience less childhood cancer than singletons. The risk reduction is most marked for Wilms tumour but may, to a varying extent, be true for a number of childhood neoplasms.

A new technique for detecting oncogene activation based on immunoblotting for oncogene proteins in serum has been applied to screen a cohort of foundry workers with well-defined workplace exposures to polycyclic aromatic hydrocarbon carcinogens. Three of the 18 individuals screened were found to have abnormal expression of the proteins of the ras and fes oncogenes. These three individuals were known to have had medium to high workplace exposures to benzo(a)pyrene and to have correspondingly high levels of benzo(a)pyrene-DNA adducts in their peripheral leukocytes. No individuals among the unexposed controls were found to have abnormal serum oncogene protein expression. These results suggest the feasibility of using serum oncogene proteins along with DNA-carcinogen adducts as potential molecular epidemiological markers in exposed worker populations; further, larger scale studies will be necessary to demonstrate the utility of these markers for identifying individuals at risk for the development of malignant disease due to their occupational exposures.

Basal cell carcinoma (BCC) is one of the most common neoplasms in the world. Development of BCC is associated with environmental factors (especially sun exposure) as well as heritable factors.To analyse three single nucleotide polymorphisms (SNPs) in the promoter regions of interleukin (IL) genes in genomic DNA from 527 cases of BCC and 530 matched controls and to examine if DNA pooling is a useful method on which to base decisions regarding further SNP analysis.The SNPs analysed were IL6-597, IL10-1082 and IL1B-511. The SNPs were first analysed from pooled DNA and afterwards from individual samples. The DNA pools resulted from a division of the samples into cases and controls, female and male, and three age groups. In these pools the allele frequencies were estimated by two methods, real-time polymerase chain reaction with allele-specific primers, and quantitative sequencing.No significant association was found when the allele frequencies in cases and controls were compared. However, by analysis of the individual genotypes we found SNP IL6-597 G/A to be significantly associated with BCC risk (P =0.007). Hereby the heterozygous genotype 'GA' had a protective effect (odds ratio 0.64, 95% confidence interval 0.49-0.84). No significant association was found for IL10-1082 and IL1B-511.The association of SNP IL6-597 with BCC could be found only by individual genotyping, but would have been missed if only data from the pooling analysis had been known.

1-SO-adenine DNA adducts, DNA single-strand breaks (SBs), chromosomal aberrations (CAs), mutant frequency (MF) at the HPRT gene, and immune parameters (hematological and of humoral immunity) were studied in styrene-exposed human subjects and controls. Results were correlated with genetic polymorphisms in DNA repair genes (XPD, exon 23, XPG, exon 15, XPC, exon 15, XRCC1, exon 10, XRCC3, exon 7) and cell cycle gene cyclin D1. Results for biomarkers of genotoxicity after stratification for the different DNA repair genetic polymorphisms showed that the polymorphism in exon 23 of the XPD gene modulates levels of chromosomal and DNA damage, HPRT MF, and moderately affects DNA adduct levels. The highest levels of biomarkers were associated with the wild-type homozygous AA genotype. The exposed individuals with the wild-type GG genotype for XRCC1 gene exhibited the lowest CA frequencies, compared to those with an A allele (P0.05). Cyclin D1 polymorphism seems to modulate the number of leukocytes and lymphocytes in the analyzed subjects. The number of eosinophiles was positively associated with XPD variant C allele and negatively with XRCC1 variant A allele (P0.05) and XPC variant C allele (P0.05). Immunoglobulin IgA was positively associated with an XRCC3 variant T allele (P0.01) and negatively with XPC variant C allele (P0.05). Both C3- and C4-complement components were lower in individuals with XRCC3 CT (P0.05) and TT genotypes (P0.01). Adhesion molecules sL-selectin and sICAM-1 were associated with XPC genotype (P0.05). Individual susceptibility may be reflected in genotoxic and immunotoxic responses to environmental and occupational exposures to xenobiotics.

Renal cell cancer (RCC) accounts for 80–90% of all cancers of the kidney.1 Clear cell carcinoma is the most common cell type among parenchymal adenocarcinomas.2,3 Over 2% of Swedish RCC patients have a parent with RCC, and the familial risk has been about 1.6.4,5 RCC is a manifestation in von Hippel Lindau (VHL) syndrome, in which up to one half of the mutation carriers of the VHL gene are thought to be affected; central nervous system hemangioblastomas and ocular angiomas are other common manifestations in VHL disease.6–9 VHL related tumours are of clear cell type, as are tumours in rare familial clusters with or without chromosome 3 translocations and other syndromes with manifested RCC, such as tuberous sclerosis, Birt-Hogg-Dube syndrome, and hereditary non-polyposis colorectal cancer (HNPCC).2,10,11 Common to these known syndromes is an apparently dominant mode of inheritance. However, in the population-based studies on familial aggregation, some evidence has been presented that the risk for RCC among siblings could be higher than that between offspring and parents, which could indicate some contribution by a recessive mode of inheritance.12,13 Intriguingly, to our knowledge, the Swedish data, together with recent Icelandic data, are the only population-based RCC studies where sibling risks have been assessed, and both point to higher familial risks among siblings than among parents and offspring.14 The most recent update (from the year 2002) of the Swedish Family-Cancer Database was used to examine specifically the issue of possible recessive inheritance in RCC. This database includes data from Swedish families, totalling over 10.2 million individuals, and cancers from the Swedish Cancer Registry up to the year 2000 and was created by linking registers maintained at Statistics Sweden and the Swedish Cancer Registry; it therefore …

We wanted to carry out a population-based study on medullary thyroid cancer (MTC) in order to quantify familial risks.MTC was studied in the Swedish Family-Cancer Database, updated in 1999 to cover individuals and offspring, born after 1934 with their biological parents, totaling 9.6 million persons. Cancer data were obtained from the Swedish Cancer Registry from year 1958 to 1996 and included 2,435 thyroid cancers among offspring.65 offspring were identified with MTC, which was coded as a separate entity since 1985. 62% had neither affected parent nor sib. Most familial cases were diagnosed at ages 15 to 24 and sporadic cases 25 years later. The familial SIRs of MTC were 3,080 and 3,650 when either a parent or a sib had MTC; when both had MTC the SIR was 35,800. All the familial risks were highest in young age groups, 0-9 years. MEN 2 or MEN 2-like families were considered when one family member had a TC and an adrenal pheochromocytoma. SIR of MTC in offspring was 61,000 when a parent had a MEN 2-like cancer and a sib had MTC.We described familial and sporadic MTC in a population-based database. The familial risks of MTC may be the highest ever reported in population based studies.

Successes in cancer therapy have led to increasing numbers of cancer survivors, who are at risk of developing second primary cancers. Therapy- or disease-induced suppression of the immune function may predispose cancer patients to a second malignancy. An excess of squamous cell skin cancers (SCC) and non-Hodgkin's lymphomas has been found in immunosuppressed patients. We used the nationwide Swedish Family-Cancer Database on 10.2 million individuals to calculate the risk of second primary skin cancers and non-Hodgkin's lymphomas following a previous malignancy. A total of 4301 second skin cancers and 1672 non-Hodgkin's lymphomas were identified. Standardised incidence ratios (SIR)s and 95% Confidence Intervals (CIs) were calculated and compared. Among 14 different sites for male or female first primary malignancies, 11 of these sites were followed by an increased risk of skin cancer (SIRs for males for risk of skin cancer as a second primary cancer: 14.1 for SCC; 9.7 for melanoma; 6.1 for leukaemia as the first site; SIRs for females for risk of skin cancer: 14.6 for SCC; 6.8 for larynx; 6.2 for upper aerodigestive tract (UADT) as the first site). The risk of non-Hodgkin's lymphoma was increased after 10 of 14 different male neoplasms and 12 of 17 different female neoplasms. (SIRs for males for risk of non-Hodgkin's lymphoma as a second primary cancer: 6.4 for non-Hodgkin's lymphoma; 3.2 for leukaemias; 3.1 for multiple myeloma as the first site; SIRs for females for risk of non-Hodgkin's lymphoma as a second primary cancer: 12.5 for leukaemias; 7.0 for Hodgkin's disease; 3.6 for UADT as the first site). The high, and after certain sites, very high risks of second skin cancer and non-Hodgkin's lymphoma suggest that immune suppression may be a contributory mechanism.

Cancer is a genetic disease in which the malignant cells have undergone mutations and chromosomal alterations that maintain the transformed phenotype even when cultured or when injected in immunologically tolerant experimental animals (Hanahan and Weinberg 2000; Vogelstein and Kinzler 1998). Yet, the views about the environmental (somatic) and inherited origin of the genetic alterations in human cancer have been debated and any reasonable agreement can be reached only when the causation appears clear, i.e., in case of a hereditary cancer syndrome or an overwhelming environmental cause, such as tobacco smoking or human papilloma virus. Even in such cases, one type of causation may not be pure, and when interactions exist, it may be impossible to apportion causation (Rothman and Greenland 1998). In the present chapter I will discuss causes of cancer, keeping in mind that, due to interactions, some of the quantitative measures may be imprecise and even arbitrary. Even so, an understanding of these causes will be helpful for scientific, clinical, and cancer preventive measures. A certain notion of cancer causation, often implicit, underlies many science and health policy decisions.

In this report we present the results of mutational analysis of the CDKN2B, CDKN2C, CDK4, p53 genes and 5'UTR of the CDKN2A gene in a set of 44 sporadic primary melanomas, which had been earlier analysed for mutations in the CDKN2A (p16/p14(ARF)) gene. No tumour-associated mutations were detected except in 1 melanoma where we found a CCT* deletion-mutation in the codon 151-152 (exon 5) of the p53 gene. On the basis of our preliminary results, we did extended genotyping of the 500 CG and 540 CT polymorphisms in the 3'UTR of the CDKN2A gene in 229 melanoma cases and 235 controls. The T-allele frequency (for 540 CT polymorphism) in melanomas was significantly higher than in controls (0.14 vs. 0.08; chi(2) = 5.95, p = 0.01; OR = 1.71, 95%CI = 1.11-2.66). The heterozygote frequency for this polymorphism was 0.26 (59/229) in melanomas compared to 0.13 (30/235) in healthy controls (chi(2) = 11.4; p = 0.0007; OR = 2.34, 95% CI = 1.40-3.92). The frequency of the 500 CG polymorphism in the 3'UTR in the CDKN2A gene was not significantly higher in melanomas compared to healthy controls. The 500 CG polymorphism, however, was in linkage disequilibrium with approximately 50 kb apart the CA intronic polymorphism in the CDKN2B gene (determined in 44 melanomas and 90 controls; Fisher exact test, p0.0001). Finally, the sequence analysis of genomic DNA isolated from T cell lymphocytes of healthy individuals exhibited that the codon reported as last of exon 2 of the CDKN2C gene is rather the first codon of exon 3.

The nationwide Swedish Family-Cancer Database of 9.6 million individuals was used to analyse the development of second neoplasia after 6909 thyroid and 12697 other endocrine tumours. Tumour cases were retrieved from the Swedish Cancer Registry from 1958 to 1996. The risk of a second endocrine tumour was markedly increased compared with first endocrine tumour; e.g. the standardised incidence ratios (SIRs) were well over 10 for adrenal tumours after thyroid cancer, and vice versa. Familial risks were higher for the development of second compared with first neoplasms, and the SIRs for men were usually higher than those for women. Many increases between different endocrine glands can probably be ascribed to known cancer syndromes. Even cancers at some other sites were increased after the development of primary endocrine tumours. Notably, small intestinal carcinoids were increased after thyroid and other endocrine tumours, and brain menigiomas were increased after parathyroid and pituitary adenomas. These novel associations suggest shared risk factors for these sites. However, many endocrine tumours are benign and the diagnosis of the first tumour may increase the likelihood of a second diagnosis.

Second cancers were studied among 68,104 cases of colorectal cancer (CRC) from the Swedish Family-Cancer Database. A total of 1,113 patients received a diagnosis of second CRC; 25 of them had a family history of CRC. Cases of second CRC with a family history were diagnosed up to 10 years before sporadic cases. The relative risk (RR) of all second CRCs was 2.21 compared with the first CRC. Familial second CRCs had a 2-fold risk compared with the sporadic forms. Age of onset was the most important covariate of second CRCs; the relative risk at ages 15-39 years was 27 compared with the first CRC. Familial CRC was associated with a high risk of small-intestinal, endometrial, and gastric cancers apart from CRC, all typical of hereditary nonpolyposis CRC (HNPCC). Among familial cases, 36% of second CRCs and 100% of endometrial cancers came from families that fulfilled the Bethesda criteria for HNPCC. Only 12 families conformed to the Amsterdam criteria; in family members, the risk of second CRC was 127-fold and that of endometrial cancer 257-fold. Other sites that were in excess among all second cancers were many cancers linked to HNPCC and, additionally, breast, prostate, thyroid and other endocrine, skin, and genital cancers. The high risk of second cancer after early-onset CRC calls for evaluation of family history and clinical surveillance.

To determine some of the genetic alterations involved in the pathogenesis and progression of transitional cell carcinoma of the bladder. Materials and methods In a population-based study, freshly frozen tissue was collected from all patients newly diagnosed with urinary bladder cancer in the Stockholm region during 1995-1996. The prevalence of loss of heterozygosity (LOH) was assessed at seven sites on chromosome 3, analysed in 151 patients, using a fluorescent multiplex polymerase chain reaction based on DNA from the tumour and peripheral blood.LOH was detected in 12.1% (at 3q25-26.2) to 22.1% (at 3p11-12) of the informative cases. Relatively frequent LOH was detected at 3p22-24.2 (21.6%), at 3p14.2 within FHIT (21.5%), and at 3p11-12 (22.1%). Of 151 tumours, 72 (47.7%) showed LOH at one or more loci on chromosome 3. LOH on chromosome 3 was weakly associated with tumour grade (P = 0.095), but not with tumour stage (P = 0.701). However, when the frequency of LOH was analysed individually at each site, the prevalence of LOH at 3p11-12 was closely correlated with higher tumour stage (P = 0.011). Replication errors were detected in only four of 151 (2.6%) tumours. Conclusion These findings suggest that the 3p11-12 locus may involve a putative candidate tumour-suppressor gene which might be associated with bladder tumour invasiveness. The FHIT gene locus showed a relatively high frequency of LOH even in Ta tumours.

We used the nationwide Swedish Family-Cancer Database to analyze the risk for adult (15-61 years) brain tumors in offspring through parental cancer probands. Additionally, cancer risks were assessed among siblings of brain tumor probands.In offspring and parents, respectively, 5,425 and 20,938 cases of brain tumors were diagnosed between the years 1958 and 1996. Groups of offspring were compared by calculating standardized incidence ratios (SIRs) for brain tumors.Of brain tumor patients, 2.1% had a parent with nervous system cancer; SIRs were 1.7, 2.4, and 2.5 for all brain tumors, astrocytomas, and meningiomas, respectively. Parental endometrial cancer and melanoma were associated with offspring astrocytoma, and parental breast and thyroid cancers with offspring ependymoma and neurinoma, respectively. SIR for sibling nervous system tumors from brain tumor probands was not increased overall but was 2.5 in those diagnosed at ages 15-34 years.These data show a familial risk for brain tumors among adults.

Human and experimental evidence indicates that the developing fetus may be more susceptible than the adult to the effects of certain carcinogens, including some polycyclic aromatic hydrocarbons (PAHs). Factors that can modulate susceptibility include proliferation rates, detoxification capabilities, and DNA repair capacity. Biomarkers can facilitate quantification of age-related susceptibility among human populations. In this study, we report on three biomarkers measured in paired blood samples collected at birth from 160 Polish mothers and newborns: 70 pairs from Krakow (a city with high air pollution including PAHs) and 90 pairs from Limanowa (an area with lower ambient pollution but greater indoor coal use). Biomarkers were: WBC aromatic-DNA adducts by (32)P-postlabeling and PAH-DNA adducts by ELISA (as indicators of DNA damage from PAHs and other aromatics) and plasma cotinine (as an internal dosimeter of cigarette smoke). Correlations were assessed by Spearman's rank test, and differences in biomarker levels were assessed by the Wilcoxon signed-ranks test. A significant correlation between paired newborn/maternal samples was seen for aromatic-DNA adduct levels (r = 0.3; P0.001) and plasma cotinine (r = 0.8; P0.001) but not PAH-DNA adduct levels (r = 0.14; P = 0.13). Among the total cohort, levels of the three biomarkers were higher in newborn samples compared with paired maternal samples. The difference was significant for aromatic-DNA adduct levels (16.6 +/- 12.5 versus 14.21 +/- 15.4/10(8) nucleotides; P = 0.002) and plasma cotinine (14.2 +/- 35.5 versus 8.3 +/- 24.5 ng/ml; P0.001) but not for PAH-DNA adduct levels (7.9 +/- 9.9 versus 5.9 +/- 8.2/10(8) nucleotides; P = 0.13). When analyses were restricted to the 80 mother/newborn pairs from whom the blood sample was drawn concurrently (within 1 h of each other), levels of all of the three biomarkers were significantly higher in the newborn compared with paired maternal blood samples (P0.05). Results suggest reduced detoxification capabilities and increased susceptibility of the fetus to DNA damage, especially in light of experimental evidence that transplacental exposures to PAHs are 10-fold lower than paired maternal exposures. The results have implications for risk assessment, which currently does not adequately account for sensitive subsets of the population.

Comparisons of cancer risks in persons by sibling cancers and those by parental cancers are informative of elucidating the potential genetic modes in the etiology of the cancers. The Swedish Family-Cancer Database was used to systematically estimate the effects of parental and sibling cancers on the cancer risks in the individuals born after 1934 (offspring). The study population included 5,520,756 offspring and their parents from 2,112,616 nuclear families. Standardized incidence ratios (SIRs) were calculated to analyze the risks for cancers in offspring by parental cancers (offspring risk) and by sibling cancers (sibling risk). For 20 concordant sites, all offspring and sibling risks were significantly increased except for sibling risks for squamous cell carcinoma of the skin and myeloma. Apart from breast cancer, the SIRs were more than 10 when offspring had both an affected parent and an affected sib at the concordant site. The ratio for the sibling to offspring risk was around 2.0 or more for gastric, renal, non-thyroid endocrine, urinary bladder, colon, testicular and prostate cancers and leukemia. For discordant sites, many reported across-site associations were confirmed and several consistent novel associations (rectum-skin, breast-endocrine and lung-endocrine) were found only among sibs. Our findings suggested that low-penetrance polygenic dominant effects or dominant genes of high penetrance but low mutant allele frequency in the population may be involved in the observed familial cancers at many sites. Recessive or X-linked effects may contribute particularly to gastric, renal, non-thyroid endocrine, bladder, colon, testicular and prostate cancers and leukemia. The search for pleiotropic recessive/X-linked susceptibility genes should be well motivated based on our results.

We have developed a 32P-postlabelling method for quantifying ultraviolet irradiation (UV)-induced cyclobutane dimers and 6-4 photoproducts in human skin in situ. We review the application of the method in studies with human volunteers, demonstrating dose-response relationships over a wide range of administered doses, repair kinetics of UV-damaged DNA among healthy individuals and melanoma patients, and modulation by sunscreens, tan and constitutive pigmentation of damage induction. A notable finding is the wide interindividual variation in DNA damage immediately after irradiation and in its repair. Moreover, the protective effects of sunscreens against erythema and DNA damage also show wide interindividual variation. These results cannot be explained by variation in the experimental methods used. The worst-case scenario is that the differences between individuals are multiplicative, resulting in 1000-fold differences in sensitivity in the population, which would be likely to translate into differences in risk of skin cancer.

Cancer has predominant environmental and somatic causes but the assessment of hereditary (genetic) causes is difficult, except for highly penetrant single-gene causes. Family studies are only partially informative in this regard because family members share diet and life-styles. Twin studies have been classically used to disentangle the effects of heredity and environment on disease etiology. We estimate the genetic and environmental components in colorectal and lung cancer and melanoma by comparing cancer risks in family members. The Swedish Family-Cancer Database, comprising more than 6 million individuals, was used as the source of family and cancer data. Tetrachoric correlations were used to describe similarity in cancer liability among family members. Structural equation modelling was used to derive estimates of the importance of genetic and environmental effects. The estimated genetic component ranged from 10% in colon and colorectal cancer to 18% in melanoma. For lung cancer, the share was 14%. If assortative mating were important for liability to cancer, these heritability estimates may be an underestimation of the true genetic effects. Non-shared environmental effect was 67-68% in colorectal cancer and melanoma, and 71% in lung cancer. Shared and childhood environments were equally important in colorectal cancer and melanoma, whereas no childhood effect was observed for lung cancer.

Ultraviolet (UV) radiation is mutagenic and induces specific DNA lesions in human skin that are often found at dipyrimidine sites. These photoproducts are likely to be biologically relevant regarding skin carcinogenesis, as p53 mutations in skin tumours are most often found at these UV radiation-specific sites within DNA. Psoriasis patients receiving long-term phototherapy are at an increased risk of non-melanoma skin cancers.The aim of this study was to quantify DNA photoproducts in human epidermis in vivo following consecutive doses of UVB and to investigate variations in DNA damage according to skin type, UVB dose and age.Eleven psoriasis patients receiving UVB phototherapy three times a week were recruited and underwent skin biopsies on a non-sun-exposed site before starting phototherapy and after three, nine and 18 UVB exposures. A biopsy was also taken at least 4 weeks after stopping phototherapy. DNA was extracted from separated epidermis and three types of photoproducts were quantified using a novel 32P high-performance liquid chromatographic technique.The mean level of cyclobutane dipyrimidine dimers (CPDs) after three doses of UVB (dose range 0.03-0.15 J cm-2) was 3.2 (range 0.8-8.9) photoproducts per 106 normal nucleotides for TT=T dimers and 4.5 (range 0-14) per 106 normal nucleotides for TT=C dimers. The mean levels of TT-C 6-4 photoproducts after three doses of UVB were very low (0.2, range 0-1.8). Overall, the levels of TT=T and TT=C reached a plateau at three exposures and were found to decrease for subsequent exposures despite increasing UVB doses. Skin type was negatively associated with mean levels of CPDs. However, significant differences in levels of photoproducts were seen between individuals, even after adjusting for skin type. No association was found between challenge dose of UVB and photoproduct yield in this study.This study showed a great individual variation in the accumulation of DNA photoproducts following exposure to repetitive doses of UVB. Photoadaptive responses of human skin involving DNA repair, tanning and epidermal thickening are likely to explain the overall lack of increase in DNA lesions throughout phototherapy. This in vivo study confirms that psoriasis patients produce a significant amount of DNA photolesions at suberythemal doses of UVB. Further work is needed to investigate which host factors are most likely to predict susceptibility to UV radiation-induced DNA damage.

The nationwide Swedish Family-Cancer Database was used to analyse the risk of cancer among the offspring of bilateral breast cancer patients. We studied 4,734 such mothers who had 9,391 offspring, of whom 328 presented with a primary cancer in the years 1958-1996. Standardised incidence ratios (SIRs) were increased for breast [SIR 3.05, 95% confidence interval (CI) 2.57-3.59], ovarian (SIR 1.84, 95% CI 1.03-3.05) and anogenital (SIR 1.75, 95% CI 1.11-2.63) cancers and childhood sarcomas (SIR 9.39, 95% CI 1.93-29.13). Additionally, squamous-cell skin cancer was increased among sons and all childhood cancers among daughters. When analysed by histological type, adenocarcinomas of the breast and ovary, all squamous-cell carcinomas and tumours at glandular epithelium (seminomas and intestinal carcinoids) were increased. Mothers with bilateral breast cancer had an excess of 2 or more children with cancer. The increased risk of ovarian cancer is consistent with germline mutations in the BRCA1 and BRCA2 genes, while the risk of soft tissue and bone sarcomas may reflect the association of these tumours with Li-Fraumeni syndrome. The increases in squamous-cell carcinomas at many sites may reflect a new susceptibility syndrome.

We have developed a fast single-strand conformation polymorphism (SSCP) technique to screen for mutations and polymorphisms in exons 5-8 of the human tumor suppressor gene p53. We use multiplex polymerase chain reaction (PCR) to amplify the four exons in one single PCR reaction and then fluorescent SSCP for screening. p53 fragments are labeled with three different colors and a fourth color is used for an internal size marker calibrating the gel. The method was evaluated in two ways: (i) 16 different cell lines with known mutations were tested blindly for band-shifts with SSCP, and (ii) 32 human urinary bladder cancer samples were screened for mutations using the present technique. After screening for mutations all exons from all samples were sequenced, both sense as well as antisense strands. Evaluating the method with four different gels shows that 21/23 mutations and polymorphism were detected in the cell lines and that 10/10 mutations and polymorphisms were detected in the patient samples. Sensitivity, specificity, positive and negative predictive values were 91/100%, 88/ 97%. 78/77% and 96/100% for cell lines / patient samples, respectively. Sensitivity, using one SSCP gel only, was 87% (20/23) for cell lines and 90% (9/10) for patient samples. We conclude that our modified SSCP technique is efficient and has a sensitivity close to 100% in detecting mutations.

The purpose of these guidelines is to provide concise guidance on the planning, performing and interpretation of studies to monitor groups or individuals exposed to genotoxic agents. Most human carcinogens are genotoxic but not all genotoxic agents have been shown to be carcinogenic in humans. Although the main interest in these studies is due to the association of genotoxicity with carcinogenicity, there is also an inherent interest in monitoring human genotoxicity independently of cancer as an endpoint. The most often studied genotoxicity endpoints have been selected for inclusion in this document and they are structural and numerical chromosomal aberrations assessed using cytogenetic methods (classical chromosomal aberration analysis (CA), fluorescence in situ hybridisation (FISH), micronuclei (MN)); DNA damage (adducts, strand breaks, crosslinking, alkali-labile sites) assessed using bio-chemical/electrophoretic assays or sister chromatid exchanges (SCE); protein adducts; and hypoxanthine-guanine phosphoribosyltransferase (HPRT) mutations. The document does not consider germ cells or gene mutation assays other than HPRT or markers of oxidative stress, which have been applied on a more limited scale.

Glutathione S-transferases (GSTs) are an important part of the protection system against a wide range of potentially harmful chemical compounds. GSTP1 and GSTM1 are mainly involved in detoxification reactions of PAH carcinogenic intermediates produced by cytochrome P450 (CYP). Polymorphism of the GST genes may influence the level of carcinogen-DNA adducts in human tissues and be associated with individual susceptibility to carcinogens. In this study, we examined the effect of common polymorphism in exon 5 (105Ile --Val) of the GSTP1 gene, alone and in combination with GSTM1-deletion polymorphism, on the level of PAH-DNA adducts measured by (32)P-postlabeling assay in mononuclear white blood cells collected in winter and in summer from a total of 170 healthy volunteers. When GSTP1 genotypes alone were compared, no statistically significant differences in adduct levels were found. However, smokers with GSTM1(null)/GSTP1-AG or -GG combined genotype showed significantly higher adduct levels in summer than carriers of other GSTM1/GSTP1 combinations (5.60 +/- 5.10 vs. 3.45 +/- 4. 28/10(8) nucleotides, P = 0.015). Among smokers carrying GSTP1-AG or -GG genotype, individuals with GSTM1(null) genotype had a significantly higher level of adducts in summer than subjects with GSTM1(+) genotype (5.60 +/- 5.10 vs. 1.82 +/- 1.98/10(8), P = 0.002) and GSTM1(null)/GSTP1-AA genotype carriers (5.60 +/- 5.10 vs. 4.13 +/- 5.84/10(8), P = 0.03). When adduct levels measured either in winter or in the nonsmoker group were considered, no influence of GSTM1/GSTP1 genotypes was found. Our data show that the combined GSTM1 and GSTP1 genetic polymorphisms may modulate PAH-DNA adduct levels in mononuclear WBCs from individuals exposed to specific carcinogenic compounds, e.g., tobacco smoke, in relatively lower-exposure environmental conditions (i.e., in summer).

FC1271a is a novel triphenylethylene compound with a tissue-selective profile of estrogen agonistic and weak antagonistic effects. It specifically binds to the estrogen receptor alpha and beta with affinity closely similar to that of toremifene and tamoxifen. To study the in vivo effects of the compound, 4-month-old rats were sham operated (sham) or ovariectomized (OVX) and treated daily for 4 weeks with various doses of FC1271a or vehicle (orally). FC1271a was able to oppose OVX-induced bone loss by maintaining the trabecular bone volume of the distal femur. Accordingly, the OVX-induced loss of bone strength was prevented at doses of 1 and 10 mg/kg. FC1271a also prevented the OVX-induced increase in serum cholesterol in a dose-dependent manner. No significant changes in uterine wet weight or morphology were observed in the OVX-rats treated with 0.1 or 1 mg/kg FC1271a, but at a dose of 10 mg/kg it had a slightly estrogenic effect. In immature rats the effect of FC1271a on uterine wet weight was less stimulatory than that of toremifene or tamoxifen, but more stimulatory than that of raloxifene or droloxifene. The appearance of the dimethylbenzanthracene (DMBA)-induced mammary tumors was inhibited by treatment of DMBA-treated rats with FC1271a in a dose-dependent manner. In human MCF-7 breast cancer cell tumors raised in nude mice in the presence of estrogen, the growth and expression of pS2 marker gene could not be maintained after estrogen withdrawal by treatment with FC1271a. No formation of DNA adducts was observed in the liver of the FC1271a-treated rats. In conclusion, the bone-sparing, antitumor, and cholesterol-lowering effects of FC1271a combined with a low uterotropic activity and lack of liver toxicity indicate that FC1271a could be an important alternative in planning antiosteoporosis therapy for estrogen deficiency.

A C--T polymorphism in intron 7 of the human tumour suppressor gene p53 was studied in 159 urinary bladder cancer patients and 171 non-cancer controls. The polymorphism was found in 15% of both patients and controls, suggesting that it has no relevance in urinary bladder cancer pathogenesis or aetiology. A second polymorphism, a T--G change located 20 bp downstream of the C--T change, was found in all samples with the C--T change. Our findings indicate that the C--T and the T--G changes occur simultaneously and belong to the same allelotype.

Abundant complex DNA adducts can be detected in human tissues by a combined 32P-postlabelling and high-performance liquid chromatography (HPLC) method. The HPLC profiles reveal a panorama of nuclease P1-resistant human adducts, which are not among the known human DNA adducts and are suspected of being endogenous. Lipid peroxidation-induced DNA adducts and I-compounds are two possible candidates for these adducts. Therefore, we performed two experiments: one was to identify chromatographically the lipid peroxidation-induced adducts among other human adducts with two acrolein- and crotonaldehyde-derived propano adduct standards (Acr-dG3 and Cro-dG12) and a structurally unknown adduct (Cro-DNA) derived from crotonaldehyde-treated DNA; and the other was to analyse the adducts in breast tissue from patients with breast cancer and from controls and to compare their behaviour with that of I-compounds in cancerous tissues. In the first experiment, Acr-dG3 and Cro-dG1 were detected in three human lung tissues, at levels ranging from 3.4 to 8.9 (x 10(-8)) and from not detectable to 2.9 (x 10(-8)), respectively. Acr-dG3 and Cro-DNA were detected in three human colon tissues, at levels of 0.2-0.4 (x 10(-8)) and 1.2-3.4 (x 10(-8)), respectively. In the second experiment, adjacent and tumorous breast tissues from 15 patients with breast cancer (of an average age of 33.4 years) and normal breast tissue from 18 controls (of an average age of 57.3) were analysed for the abundant complex adducts. The total adduct levels in the adjacent and tumorous tissues were lower than in the normal tissues (with medians of 8.0, 11.8 and 13.3 (x 10(-7)), respectively). Significant differences in the adduct levels between adjacent or tumorous tissues and normal tissues were observed in three HPLC peaks, and age was significantly associated with three peaks. These results are consistent with our speculation that the abundant adducts are comprised of lipid peroxidation-induced adducts and human homologues of I-compounds.

Endometrial cancer was studied in the Swedish Family-Cancer Database, updated in 1999 to cover individuals born after 1934 with their biological parents, totaling 9.6 million persons. Cancer data were obtained from the Swedish Cancer Registry from 1958 to 1996 and included over 20,000 cases of endometrial cancer. Seventy-six families were identified in which both the mother and the daughter had endometrial cancer, giving a familial standardized incidence ratio (SIR) of 3.19 for daughters and 2.78 for mothers. The risk depended inversely on the age at diagnosis, and the risk was almost 10 in daughters who were diagnosed before age 50 when their mothers were also diagnosed before that age. The discordant cancer site that associated with endometrial cancer between the two generations was colon, with a SIR of 1.44-1.68. However, when the maternal endometrial cancer was diagnosed before age 50, increased SIRs were observed in daughters or sons for rectal, pancreatic, nervous system, breast, and ovarian cancers. Second cancers were followed in females diagnosed with endometrial cancer, and the highest overall risks were observed for ovarian and connective tissue cancers; colorectal cancers were also clearly in excess. Among the other family members of the 76 families in which both mother and daughter were affected with endometrial cancer, there were 11 cases of colorectal cancer. When a sister was affected in such families, the SIR of endometrial cancer was 31.40, and the median diagnostic age was several years lower than in endometrial cancer families in which no colorectal cancers were found. Many of these families may have hereditary nonpolyposis colorectal carcinoma syndrome. However, the risk of endometrial cancer was increased even in families presenting no colorectal cancers.

Environmental contamination by polycyclic aromatic hydrocarbons (PAH) and human exposure were surveyed in the east Baltic region. Polluted and heavily industrialized areas are upper Silesia in Poland, northern Bohemia in the Czech Republic, and the northeast part of Estonia. In Estonia the pollution is in a defined geographic area, where lung cancer incidence is higher than elsewhere. In Silesia, exposure of some 5 million people appears to be elevated; DNA (deoxyribonucleic acid) adduct levels in white blood cells are increased in groups of residents with apparently only environmental exposure. By extrapolation, some 150 annual lung cancer cases could be predicted due to PAH in Silesia. Air levels of benzo[a]pyrene were increased in northern Bohemia, and domestic heating and power plants using brown coal appeared to be major contributors to particulate air pollution in winter. Further studies are needed to assess health risks of PAH exposure in central and eastern Europe.