K Hemminki

..0 are known to present with lung manifestations, suggesting that the autoimmune process contributes to lung cancer susceptibility. The data on survival are reassuring that autoimmune diseases do not influence prognosis in lung cancer...

..abstract:..

..Importantly, half of all site-specific cancer deaths (266/530) were due to lung tumors. Thus, an intense search should be mounted to find lung cancer in CUP patients with lymph node metastases...

..Amyloidosis is a heterogeneous disease caused by deposition of amyloid fibrils in organs and thereby interfering with physiological functions. Hardly any incidence data are available and most survival data are limited to specialist clinics...

..Patients with autoimmune (AI) diseases are diagnosed with increased frequencies of some cancers, which may depend on the underlying dysregulation of the immune system or treatment. Data on female cancers are limited...

..Based on our previous results on co-morbidity between leukemia and T1D, we updated the Swedish dataset and focused on early onset leukemias in patients who had been hospitalized for T1D, comparing to those not hospitalized for T1D...

..Yet, a population level search for shared susceptibility between discordant cancers has been hampered because of lacking population sizes...

..Although there are putative mechanistic links between obesity and autoimmune diseases, obesity is not considered a risk factor for most autoimmune diseases...

..We analyzed systematically the occurrence of histology-specific digestive tract cancers in patients diagnosed with 33 different autoimmune diseases in order to address the question of shared susceptibility...

..We want to use the detection rate of second cancers as a measure of efficacy of the diagnostic modalities in finding tumors, assuming that the detection rates have increased with modern technologies...

..In the present review, I focus on three lines of family studies with novel results...

....

..TAS2R14 is one of the better characterized members of the taste receptor family and has several polymorphic variants. Several substances that have been shown to activate TAS2R14 are powerful toxic and carcinogenic agents...

..Therefore, genotyping of such deletion polymorphisms in case-control studies could give important insights into risk associations...

..Accumulating evidence also indicates a role of ghrelin in cancer development...

..Inactivating and truncating mutations of the nuclear BRCA1-interacting protein 1 (BRIP1) have been shown to be the major cause of Fanconi anaemia and, due to subsequent alterations of BRCA1 function, predispose to breast cancer (BC)...

..Genetic alterations in TCF7L2 may therefore affect cancer risk. Recently, TCF7L2 variants, including the microsatellite marker DG10S478 and the nearly perfectly linked SNP rs12233372, were identified to associate with type 2 diabetes...

..However, the effects on the estimation of familial risk are so far small...

..These findings should guide future genomic studies. The high spouse correlation will be a challenge to environmental epidemiology of ALS...

..Familial associations between cancer sites may implicate true familial clustering which is relevant for the identification of new cancer syndromes and for clinical counseling...

..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...

..There are limited data available on tumour subtype-specific familial risks for nervous-system tumours. We aimed to provide such data at the population level...

..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...

..The results should encourage others working on twin and singleton populations to examine the specific associations and emerging hypotheses...

..Reliable data on familial risks are important for clinical counseling and cancer genetics...

..The data suggest that passive smoking during childhood is associated with an increase risk of nasal cancer. For bladder and kidney cancers, a contribution by tobacco carcinogens is implicated through breastfeeding and in utero exposure...

..The present data suggest that 1.7% of lung cancers up to age 68 years are heritable and probably due to a high-penetrant recessive gene or genes that predispose to tobacco carcinogens...

..The late effects of these therapeutic practices have not been properly evaluated because of the relatively short time since their application...

..Our aim was to characterize familial risks for type 2 diabetes by the type and number of affected family members, including half-siblings, adoptees, and spouses, to quantify risks and estimate the contribution of environmental effect...

....

..Clinical genetic counseling would benefit from reviewing established familial risks on all main types of cancer...

..The data are probably explained by the healthy brother seeking medical advice upon diagnosis in another brother. This effect is likely to bias familial risk estimates...

..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...

....

..We wanted to estimate the associations of ulcerative colitis (UC) and Crohn's disease (CD) with 32 autoimmune and related diseases among parents and offspring, singleton siblings, twins, and spouses...

..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...

..Although of low risk, these common variants appear to explain large proportions of breast and prostate cancers in the population...

..We wanted to estimate associations between type 1 diabetes mellitus and 33 autoimmune and related diseases in parents, offspring, singleton siblings and twins...

..The shared familial risks of MS with amyotrophic lateral sclerosis and asthma suggest shared genetic basis...

..However, the theory cannot be excluded but should be taken up for study when further data are available on maternal smoking. The high familial risk may be the product of shared childhood environment and heritable causes...

..The lack of discordant pairs may suggest that heritable factors are disorder type-specific. Affected concordant sibling pairs should be subjected to molecular studies aiming at identifying the susceptibility gene...

..77; there was no evidence of increased RRs immediately after last pregnancy. The present study is by far the largest one published on the theme. It shows that pregnancy is not an additional risk factor for women with a family history...

..The consistency of the results suggests that the prognosis in breast cancer is in part heritable which is likely to be explained by yet unknown genetic mechanisms...

..We carried out a family study on COPD in order to address the role of heritable and environmental risk factors at a population level...

..It can be described by the proportion of the familial disease, i.e. same disease in two or more family members. A family history always needs to be specified as to the number of generations covered and their ages...

..Asthma is a common disabling condition, with known environmental and familial risk factors and with their assumed interactions. We wanted to carry out a family study on asthma to address gene-environment interactions at a population level...

....

..Patients diagnosed with RA have been at an increased risk of many cancers and at a decreased risk of some cancers. We planned to revisit the theme by using a nation-wide population of RA patients...

..To prove this, we searched for familial clustering of survival (ie, concordance of survival among family members)...

..Whether these associations can be explained by the recently identified pituitary adenoma predisposing gene, AIP, remains to be established...

..Using cancer as an example of complex disease, we examine the scientific evidence for the hypothesis that human diseases result from interactions between genetic variants and the environment...

..However, the population attributable fractions of the two alleles are equal. The penetrance mode of the causative locus may be very difficult to deduce from the apparent penetrance mode of the marker locus...

..Familial clustering of a disease is an indicator of a possible heritable cause. In the era of genome scans, the consideration of data on heritability should be important in the assessment of the likely success of the scans...

....

..Patients diagnosed with Crohn disease (CD) are known to be at an increased risk of bowel cancers and lymphoma. CD is an autoimmune disease and we hypothesize that the patients are predisposed to a wider spectrum of cancers...

..The very high overall SIRs for the diseases of the myoneural junction and muscle imply that the sporadic forms of these diseases are relatively rare and these diseases are overwhelmingly heritable...

..The high familial risks for neurological disease imply heritable etiology and opportunities for identification of further susceptibility genes...

..We aim at defining familial risks for siblings to be hospitalized because of epilepsy...

....

..However, some of these, including small intestinal carcinoids, prostate cancers and nonthyroid endocrine tumors, may be in excess because of intensified medical surveillance of the patients...

..Divorce is becoming increasingly common in many countries and any deviant cancer patterns among offspring of divorced parents will have an impact on the population risk...

..To our knowledge this is a first attempt to summarize familial risks for a large number of diseases using data from a single population on which reasonable uniform diagnostic criteria have been applied...

..Familial nervous system cancers are rare and limited data on familial aspects are available particularly on site-specific tumours...

..If fatal forms of cancer are a highly familial subtype, then familial risk for mortality may exceed that of incidence, which is relevant for clinical decision making and counseling...

..Recent data have shown that family history influences survival of bladder cancer. Gene identification has been successful particularly on low-risk genes influencing susceptibility and prognosis...

..The implementation of a unified management plan for familial cancers at large will be a major challenge to the clinical genetic counselling community...

..Quantitative data on solid tumors are limited. We focus on survivors of non-Hodgkin's lymphoma (NHL) because the disease is diagnosed at a wide range of ages and treated uniformly primarily with chemotherapy...

..These factors appear to influence seminoma risk in a more enduring way than they influence non-seminoma...

..Increased surveillance and the availability of PSA screening are the likely reasons for the overestimated familial relative risk shortly after the first diagnosis. This lead time bias should be considered in clinical counselling...

..84%. Although the present analysis lacked data on some important risk factors for endometrial cancer, the results suggest that a large proportion of the etiology of endometrial cancer can be defined by known epidemiological risk factors...

..Asthma includes immunological components that may share mechanisms with autoimmune diseases. We analyzed the subsequent occurrence of any of 22 autoimmune and related conditions in hospitalized asthma patients...

..Recent data show that colonoscopy is efficient in preventing left-sided cancers only. We examine the association of Tumor Node Metastasis (TNM) classes with diagnostic age and patient characteristics...

..40 in the daughter when the mother presented with endometrial cancer. Our data show a strong familial coupling of ovarian and endometrial cancers, which appears to be specific to the endometrioid morphology...

..Cancer and type 2 diabetes (T2D) are two common diseases that may share risk factors. We aimed at determining subsequent cancer risks in patients hospitalized for T2D in Sweden...

..Such data would be valuable for prevention and gene identification strategies...

..If, for example, a familial SIR of 2.2 would be use as an action level, counseling would be needed for most cancers at some diagnostic age groups. The present data provide the basis for clinical counseling...

..These differences offer opportunities for the identification of factors underlying breast cancer etiology and tools for prevention...

..Urological cancers also offer a challenge to molecular geneticists attempting to identify the susceptibility genes underlying the familial clustering...

..No evidence for gene-environment interactions was found. The intractable difficulty in separating cervical cancer causation will be an obstacle for a successful identification of susceptibility genes...

..The strong association of pancreatic and lung cancers is puzzling, and it remains unclear to what extent this represents familial sharing of smoking habits...

..The results have implications for design of genetic studies and for clinical counselling...

..Further, the results indicate, a role for the 3' UTR polymorphisms in the CDKN2A gene in tumor invasiveness...

..Only the combined distributions of TT/AA genotypes in MTHFR exon 4 (C/T) and exon 7 (A/C) showed slight increase in BCC compared to controls (P < 0.07, OR: 1.94; 95% CI: 0.96-3.89)...

..Our results highlight effects of homozygous deletion of the CDKN2A locus on global gene expression...

..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...

..The contribution of hereditary factors to the causation of sporadic cancer is unclear. Studies of twins make it possible to estimate the overall contribution of inherited genes to the development of malignant diseases...

..38+/-7.24 vs 65.77+/-19.79 years; t-test, P=0.02). Our data suggest that the occurrence of BRAF/N-ras mutations compensate the requirement for the allelic loss at chromosome 9, which is one of the key events in melanoma...

..The possible contribution of 6A/6A homozygosity in the TGF-betaRI gene to breast cancer needs to be confirmed in an independent study...

....

..Women from Yugoslavia and Turkey had an excess of thyroid tumours. All immigrant groups showed breast, endometrial and ovarian cancers at or below the Swedish level but the differences were no more than 2-fold...

..02). We conclude that the XPD variant alleles may be associated with reduced repair of aromatic DNA adducts in general and increased lung cancer risk among never-smokers...

..The search for pleiotropic recessive/X-linked susceptibility genes should be well motivated based on our results...

..In mothers and daughters, ovarian but not colon cancer was increased in combination with breast cancer...

..Our results suggest that the CDKN2A (p16(INK4a) and p14(ARF) ) and p53 genes involved in the two cell cycle pathways are major and independent targets of inactivation in OSCC...

..Birth in Sweden sets the Swedish pattern for cancer incidence, irrespective of the nationality of descent, while entering Sweden in the 20s is already too late to influence the environmentally imprinted program for the cancer destiny...

..51 to 23.56). CONCLUSIONS: In addition to the familial association of these 2 cancer sites, the high risk of a second primary cancer of the bladder in patients with papillary renal cell carcinoma may reflect a common genetic alteration...

..10 (95% CI = 1.04 to 1.17, P = .001). Among the combined subset of 2795 familial breast cancer patients, the respective ORs were 1.27 (95% CI = 1.12 to 1.45, P = .0003) and 1.16 (95% CI = 1.06 to 1.27, P = .001)...

..33, 95% CI 1.0-1.8) in cases (C-allele 0.29) compared to controls (C-allele 0.24). Combined heterozygote and variant homozygote genotype frequency was also higher in cases than controls (chi(2) 4.79, p = 0.03; OR 1.50, 95%CI 1.04-2.16)...

..Among 182 female cases, significantly elevated SIRs were observed in glass, ceramic, and tile workers. The study identified some known risk occupations and suggested some new ones...

..The effect of the novel intronic insertion polymorphism, which is located 16 nt downstream of the 3'-end of exon 10 of the XPD gene and involves a mononucleotide C repeat sequence, on expression remains to be determined...

..The data show that the familial PAF of prostate cancer was 20.55%, and breast cancer 10.61%, but for most other sites, it was between 1 and 3%...