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K Hemminki

Publications and source records attributed to K Hemminki.

At least 37 records · Page 2Linked to original sources
PubMed2004

Methods for testing familial aggregation of diseases in population-based samples: application to Hodgkin lymphoma in Swedish registry data.

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.

Adult↗
PubMed2004

Familial risk of endometrial cancer after exclusion of families that fulfilled Amsterdam, Japanese or Bethesda criteria for HNPCC.

BACKGROUND: Endometrial cancer is the second most common lesion within hereditary non-polyposis colorectal cancer (HNPCC) syndrome. The importance of the non-HNPCC genetic predisposition to endometrial cancer is unclear, and the familial aggregation of endometrial cancer after exclusion of HNPCC families may offer valuable clues about the involvement of non-HNPCC-related genes. PATIENTS AND METHODS: The families of the nationwide Swedish Family-Cancer Database were classified as HNPCC families according to the Amsterdam I or II, the modified Amsterdam, the Japanese and the Bethesda criteria. Standardized incidence ratios (SIRs) for endometrial cancer when parents or siblings were diagnosed with cancer at the most common sites were calculated before and after exclusion of HNPCC families. RESULTS: The proportion of individuals in the families with endometrial cancer was highest when the criteria required three cancers within a family or multiple HNPCC-related cancers in the same individual. Consideration of the Amsterdam or the Japanese criteria hardly reduced the familial aggregation of endometrial cancer. After exclusion of families that fulfilled the Bethesda criteria, SIRs were significant when the parents were diagnosed with endometrial or thyroid gland cancers; 75.7% (95% confidence interval 60% to 99.1%) of the familial cases of endometrial cancer were not related to HNPCC according to the Bethesda criteria. The reduction of SIRs for cancers at the colon, pancreas, prostate and ovary was limited when the Bethesda criteria were applied. However, the Bethesda criteria identified most of the familial aggregation when endometrial cancers were diagnosed before the age of 55 years. CONCLUSIONS: The data suggest that additional effects, not related to HNPCC, contribute to the familial aggregation of endometrial cancer.

Adult↗
PubMed2004

Risk of cancer at sites other than the breast in Swedish families eligible for BRCA1 or BRCA2 mutation testing.

BACKGROUND: Population-based data on the risk of cancer in families eligible for BRCA1/2 mutation testing may help to reach a consensus about the association of BRCA1/2 mutations with cancer at sites other than the breast and may reveal new, non-BRCA1/2 related components of the familial clustering of cancer in those families. PATIENTS AND METHODS: The families of the Swedish Family-Cancer Database with at least three generations (n = 944,723) were classified according to the criteria proposed by the German Consortium for Hereditary Breast and Ovarian Cancer. The cancer incidences in the classified families were compared with the incidences in the general population. The percentages of individuals with cancer in families eligible for BRCA1/2 mutation testing were compared with data in the literature to estimate the proportion of malignancies related to BRCA1/2 mutations. RESULTS: Families with two breast cancers before the age of 50 years showed increased risk of early onset pancreatic, prostate and ovarian cancers; families with ovarian and breast cancers presented increased incidences for ovarian and ocular cancers; families with two breast cancers, at least one of them under the age of 50 years, showed increased risks of prostate and primary liver cancers. Stomach cancer before age 70 years was twice as frequent in families with breast and ovarian cancers as in the general population. BRCA1/2 mutations probably explain most of the aggregation of ovarian cancer in families with male breast cancer, and in families with at least two breast cancers diagnosed before age 50 years. CONCLUSIONS: The association of BRCA1/2 mutations with ovarian, pancreatic, prostate and stomach cancers was confirmed at a population level. However, the clustering of early pancreatic cancer in families with two breast cancers under age 50 years, the aggregation of ovarian cancer in families with breast and ovarian cancers, and the increased incidence of early onset prostate cancer in families with male breast cancer seem to be due to other effects unrelated to BRCA1/2 mutations.

Adult↗
PubMed2004

University and medical education and the risk of cancer in Sweden.

Socio-economic gradients are known to exist in cancer but we want to focus on the university-educated population and specifically on physicians to find out whether their special educational background on cancer causation helps them to avoid cancers. The analysis was based on the latest update of the Swedish Family-Cancer Database, in which the educational level was obtained from the national census of 1970 for those aged 30 years or older and the follow-up for cancer was extended up to year 2000. We determined standardized incidence ratios (SIRs), adjusted for several variables, for cancer among men and women in four educated groups and compared them with those with less than 9 years of education. Total cancer risks did not differ much, but at individual sites, the university-educated population showed consistent, increasing or decreasing trends. The educated group showed high SIRs for melanoma and skin cancer and for female breast cancer. At all these sites, SIRs for in situ tumours exceeded those for invasive tumours; the highest SIR was 4.81 for male MD, PhDs for in situ melanoma. SIR for in situ breast cancer for female physicians was 1.95. SIR for non-Hodgkin's lymphoma for male MD, PhDs was 2.20 but their risk of stomach cancer was only 0.26. Tobacco-related cancers were decreased among the educated group. Cancer risks for physicians were not different from those of their academic colleagues. Some of the increased risks were probably due to lead-time bias, caused by early diagnosis.

Adult↗
PubMed2004

Clinical genetic counselling for familial cancers requires reliable data on familial cancer risks and general action plans.

Familial cancer clustering, without obvious heritability, poses a major challenge for current cancer risk assessment and management. Reliable determination of familial risks for cancer is important for clinical genetic counselling, but medically verified data on familial risks for many malignancies have been limited. However, the nationwide Swedish Family-Cancer Database allows a reliable characterisation of familial risk for all major neoplasms. Even though alert genetic counsellors and certainly clinical cancer geneticists will consider familial cancer clustering in their purview, the standard medical referral systems, which have already been shown to be poor in capturing and referring families at high risk for heritable cancers, are unlikely to ascertain familial aggregations of other cancers that are not known to belong to an inherited cancer syndrome. The data will be helpful in implementing evidence based guidelines for helping the general medical system to ascertain and refer even familial cancer clusters to cancer genetics professionals.

Adolescent↗
PubMed2003

Familial invasive and in situ squamous cell carcinoma of the skin.

We used the updated nation-wide Swedish Family-Cancer Database to examine familial risks in data from 1961 to 1998 on 1252 invasive and 2474 in situ squamous cell carcinoma (SCC) of the skin among offspring, and over 10 times more among parents. In 259 families a parent and an offspring had skin SCC. The familial standardised incidence ratios (SIRs) were 2.72 for invasive and 2.40 for in situ skin cancers in offspring. Multiple skin cancers in parents were associated with increased SIRs for invasive SCC in offspring, being 2.55 for one and up to 14.93 for two invasive and two in situ cancers in parents; the corresponding in situ SCC risks were 2.28 and 7.49. The population attributable fraction for any familial skin SCC, invasive or in situ, was 4.1%. Melanoma was the only discordant tumour that was associated with invasive and in situ skin SCC. These results provide evidence that there is an underlying hereditary susceptibility for at least a part of the familial clustering for skin SCC.

Aged↗
PubMed2003

The role of various biomarkers in the evaluation of styrene genotoxicity.

We evaluated our data on the occupational exposure to styrene in lamination workers. The battery of parameters included markers of external and internal exposure and biomarkers of biological effects and susceptibility. DNA repair capacities have been determined in both exposed and control groups. Styrene workplace concentration significantly correlated with styrene concentration in blood, exhaled air and urinary mandelic acid. Haemoglobin and O(6)-styrene oxide (SO)-guanine DNA adducts were significantly higher in exposed subjects as compared to controls and correlated with exposure parameters. In styrene-exposed workers 1-SO-adenine DNA adducts were detected (2.6 per 10(9) dNp), while in controls these adducts were below the detection limit. 1-SO-adenine adduct levels were affected by both acute and cumulative exposure (P=0.001, F=86.0 and P=0.017, F=59.0, respectively) and associated with cytochrome P450 2E1 (CYP2E1) polymorphisms (R(2)=0.442). Mutant frequencies (MF) at the hypoxanthine-guanine phosphoribosyltransferase (HPRT) locus appeared to accumulate with exposure over time and were associated with glutathione S-transferase P1 (GSTP1) polymorphism. DNA repair capacity increased with the exposure, except for the group exposed to the highest styrene concentration. In this particular group, increased DNA repair capacity to remove oxidative DNA damage was found.

Adult↗
PubMed2003

Skin cancer and non-Hodgkin's lymphoma as second malignancies. markers of impaired immune function?

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.

Carcinoma, Squamous Cell↗
PubMed2003

Cancer risks in men who had children with different partners from the Swedish Family-Cancer Database.

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.

Aged↗
PubMed2003

Familial liver and gall bladder cancer: a nationwide epidemiological study from Sweden.

BACKGROUND AND AIMS: Familial risks in liver and biliary cancers have been assessed in small case control studies, usually based on reported, but not medically verified, cancers in family members. Thus the degree of familial clustering for these cancers remains to be established. METHODS: The nationwide Swedish Family-Cancer Database was used, covering 10.2 million individuals for the years 1961-1998 from the Swedish Cancer Registry. Liver and biliary tract cancers were identified from 1121 offspring between the ages of 0 and 66 years and 17 131 parents. Standardised incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated for cancers in family members. RESULTS: All cancers in the liver and biliary system showed a familial SIR of 1.65 (95% CI 1.05-2.46). This was mainly explained by a high risk for familial gall bladder cancer (SIR 5.21 (95% CI 2.07-10.80)) and for familial primary liver cancer with hepatocellular carcinoma histology (SIR 4.69 (95% CI 1.48-11.04)). For gall bladder and hepatocellular cancer, maternal transmission appeared to be favoured. Gall bladder cancer was associated with pancreatic cancer (SIR 2.39 (95% CI 1.23-4.18)). Primary liver cancer was associated with cervical, urinary bladder, and endocrine gland tumours. Cancer in extrahepatic bile ducts was associated with ovarian cancer and that in ampulla of Vater with thyroid cancer; however, these associations may have been fortuitous. CONCLUSIONS: This study has provided the first data on familial clustering of liver and gall bladder cancers, based on medically confirmed records. The risks were so high that heritable factors were likely to contribute, possibly modified by environmental factors. The demonstration of candidate genes would help to further characterise the familial risks.

Adolescent↗
PubMed2002

Cancer risks among long-standing spouses.

We estimated risks for concordant and discordant cancers in spouses in order to quantify cancer risks from the shared environment. The study was restricted to spouses who had one or more children in common and who lived together for at least 15 years after the first child's birth. The nation-wide Family-Cancer Database was used as the source of family and cancer data. Standardised incidence ratios were calculated for concordant and discordant cancers in spouses after 50 years of age. Among the 18 cancer sites considered, only three sites, stomach, lung and bladder, showed concordant increases of cancer among spouses, standardised incidence ratios ranging only from 1.19 to 1.38. Additionally, gastric and pancreatic cancer were associated among spouses, as did many cancers which were related to tobacco smoking or human papilloma virus infection. By contrast, standardised incidence ratios of colon, rectal, renal and skin cancers showed no increases among spouses. Shared lifestyle among family members seems to explain only a small proportion of familial cancer susceptibility. Because lifestyles are likely to differ more between parents and offspring than between spouses, familial cancer risks between parents and offspring are even more likely to be due to heritable than environmental effects.

Databases, Factual↗
PubMed2002

A case-control study of childhood leukaemia and paternal occupational contact level in rural Sweden.

In a national case-control study in Sweden, we investigated whether in rural areas (where susceptible individuals are more prevalent than in urban areas) leukaemia risk was higher among the young children of fathers with many work contacts, as the infective hypothesis has predicted. A total of 1935 cases diagnosed in 1958-1998 together with 7736 age-matched (within 1 year) population controls (of whom 970 and 3880 respectively were aged 0-4) were linked to paternal occupational details as recorded in the census closest to the year of birth. Applying the two classifications of occupational contact level used in a study of rural Scotland, the odds ratios for children aged 0-4 years in the highest contact category (which includes teachers) in the most rural Swedish counties were 3.47 (95% CI 1.54, 7.85) and 1.59 (1.07, 2.38) respectively, relative to the medium and low (reference) category; no such excess was found in urban or intermediate counties. There was also a significant positive trend at ages 0-4 in the rural counties across the three levels of increasing occupational contact (P for trend 0.02 and 0.03, respectively), but again not in the urban or intermediate counties. No such effect or trend was found at ages 5-14 in any of the three county groupings. The findings confirm those of a recent study in rural Scotland, and also suggest that unusual population mixing (as occurred in Scotland as a result of the North Sea oil industry) is not a necessary requirement for the effect, since comparable mixing has not been a feature of rural Sweden.

Adolescent↗
PubMed2002

Cancer risks in Nordic immigrants and their offspring in Sweden.

Numerous migrant studies on cancer have been carried out, but little data are available on cancer incidence upon inter-European migration. We used the nationwide Swedish Family-Cancer Database to analyse cancer risk among Nordic immigrants and their offspring in Sweden. The parental population had entered Sweden in their 20s and they had become parents in Sweden. Finns were the largest immigrant group including approximately 183,000 parents and 278,000 offspring. We calculated the standardised incidence ratios (SIRs) and 90 or 95% confidence intervals (CIs) for 26 cancer sites using native Swedes as a reference. Cancers in the first generation immigrants followed the rates in the countries of origin, reaching high SIRs for tobacco-related, cervical and testicular cancer among Danes and for stomach cancer among Finns. Only a few cancers, such as cervical cancer was increased in the second generation. At many sites, particularly among the Finns, protection was observed in the first generation. At three sites, breast, ovary and urinary bladder, where plausible evidence for protection was found even among offspring, this was not reinforced among the offspring of compatriot parents, which is inconsistent with heritable effects. Protection against melanoma was strongest among the offspring of compatriots, but the contribution of cultural factors cannot be excluded. As the parents immigrated to Sweden in their 20s, their cancer pattern, including habits and life style, appeared to be set before that age because the differences to Swedes persisted even in cancers that predominate in old age. Immigrant populations would appear to be attractive subjects to study etiological factors of cancer at sites where causes remain poorly understood, such as testicular cancer.

Denmark↗
PubMed2002

Cancer risks in women who had children with different partners from the Swedish Family-Cancer Database.

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.

Databases, Factual↗
PubMed2001

Familial colorectal adenocarcinoma from the Swedish Family-Cancer Database.

Familial risks for colorectal (CRC) adenocarcinoma were characterized from the Swedish Family-Cancer Database covering 9.6 million individuals, whose family relationships and cancers were obtained from registered sources, not sensitive to reporting or ascertainment bias. Cancer cases were retrieved from the Swedish Cancer Registry from years 1958-96. Standardized incidence ratios (SIRs) were calculated based on gender-, age-, period- and tumor type specific rates. A total of 4,794 and 67,925 CRCs were recorded in offspring and parents, respectively. For colon and rectal adenocarcinoma, the SIRs in offspring were 2.28 and 1.68 by parental CRC adenocarcinoma, giving attributable proportions of 6.45 and 3.31%, respectively. The SIR of CRC was over 10 when both offspring and parents were diagnosed at a young age. The risk for parental CRC adenocarcinoma was over 100 when 2 or more children were affected. The risk in siblings was also very high when a parent was affected. The familial cancer sites that associated with CRC were those typical of hereditary nonpolyposis colorectal cancer (HNPCC). This is the largest study published on familial CRC and the only one reporting specifically on adenocarcinoma. The data suggest that HNPCC is the largest single disease entity among CRCs, probably accounting for less than 50% of familial CRC. Other familial components appear heterogeneous, characterized by incomplete penetrance, recessive mode of inheritance and few associated tumor sites.

Adenocarcinoma↗