Monoclonal gammopathy: natural history studied with a retrospective approach

The aim of this study was to examine the natural history of monoclonal gammopathy using a retrospective approach and a long observation period. Protein electrophoresis (PE) and immunofixation (IF) was performed on frozen prediagnosis serum samples from 65 multiple myeloma (MM) and 10 Waldenstr?m's macroglobulinemia (WM) cases. Paraprotein was found in 28% and 46% of the samples from cases using PE and IF respectively. The type of paraprotein was IgA in 33.4% of cases, IgG in 57%, and IgM in 8.5%. Excluding light chain or non-secretory disease, 72 % of MM cases had a prodromal MGUS phase within 10 years of diagnosis MM and WM were preceded by MGUS in at least half of the cases, confirming the premalignant nature of this condition.     

Assessing disease risk in genome-wide association studies using family history

We show how to use reports of cancer in family members to discover additional genetic associations or confirm previous findings in genome-wide association (GWA) studies conducted in case-control, cohort, or cross-sectional studies. Our novel family history-based approach allows economical association studies for multiple cancers, without genotyping of relatives (as required in family studies), follow-up of participants (as required in cohort studies), or oversampling of specific cancer cases (as required in case-control studies). We empirically evaluate the performance of the proposed family history-based approach in studying associations with prostate and ovarian cancers, using data from GWA studies previously conducted within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. The family history-based method may be particularly useful for investigating genetic susceptibility to rare diseases for which accruing cases may be very difficult, by using disease information from nongenotyped relatives of participants in multiple case-control and cohort studies designed primarily for other purposes.     

Mortality,Reoperation, and Hospital Stay Within 90 Days of Primary and Secondary Antireflux Surgery in a Population-Based Multinational Study

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Is Smoking an Independent Risk Factor for Invasive Cervical Cancer? A Nested Case-Control Study Within Nordic Biobanks

The strong correlation between smoking and exposure to oncogenichuman papillomaviruses (HPVs) has made it difficult to verifythe independent role of smoking in cervical carcinogenesis.Thus, the authors evaluated this role. Five large Nordic serumbanks containing samples from more than 1,000,000 subjects werelinked with nationwide cancer registries (1973–2003).Serum samples were retrieved from 588 women who developed invasivecervical cancer and 2,861 matched controls. The samples wereanalyzed for cotinine (a biomarker of tobacco exposure) andantibodies to HPV types 16 and 18, herpes simplex virus type2, and Chlamydia trachomatis. Smoking was associated with therisk of squamous cell carcinoma (SCC) among HPV16- and/or HPV18-seropositiveheavy smokers (odds ratio = 2.7, 95% confidence interval: 1.7,4.3). A similar risk of SCC (odds ratio = 3.2, 95% confidenceinterval: 2.6, 4.0) was found in heavy smokers after adjustmentfor HPV16/18 antibodies. The point estimates increased withincreasing age at diagnosis and increasing cotinine level. Thisstudy confirms that smoking is an independent risk factor forcervical cancer/SCC in women infected with oncogenic HPVs. Thesefindings emphasize the importance of cervical cancer preventionamong women exposed to tobacco smoke. carcinoma, squamous cell; risk factors; smoking; uterine cervical neoplasms     

Human, mouse or rat? Species authentication of glioma-derived cell cultures

Cell culture and the use of cell lines are often fundamental requirements in basic scientific research. It is of the utmost importance for researchers to ensure that the cell lines in use have a well defined origin and are routinely re-analysed to highlight possible areas of contamination. In this preliminary study species specific primers were designed to easily distinguish between human, mouse and rat DNA with standard agarose gel electrophoresis. Inter-species contamination is often the most common form of contamination experienced, with the most common of cell lines in use being of human, mouse and rat derivation. A PCR-based assay was therefore developed to ensure an accurate, quick and cost effective means of determining any cell line contamination which could be easily executed on a routine basis. Furthermore, this simple PCR is able to identify the species in the inter-species mixture of DNA and therefore provides a valuable tool for the authentication of human cell lines.     

Relation between the human fibroblast strain 46BR and cell lines representative of Bloom's syndrome

46BR is a human fibroblast strain derived from an immunodeficient young female of stunted growth. The diploid fibroblasts as well as a Simian Virus 40-transformed cell line are hypersensitive to killing by many DNA-damaging agents, exhibit a slightly increased level of spontaneous sister chromatid exchange, and show a defect in DNA ligation in vivo. 46BR is now shown to have abnormal DNA ligase I and is similar in this regard to cell lines derived from Bloom's syndrome patients. In a direct comparison, both 46BR and several Bloom's syndrome lines were found to be hypersensitive to the cytotoxic effect of simple alkylating agents, 46BR being more markedly sensitive. Bloom's syndrome lines do not exhibit the strong delay in joining of Okazaki fragments during DNA replication characteristic of 46BR. The cell line 46BR probably has a mutation in the gene encoding DNA ligase I different from those occurring in classical cases of Bloom's syndrome.     

Familial risk of lung carcinoma in the Icelandic population

Context  The dominant role of tobacco smoke as a causative factor in lung carcinoma is well established; however, an inherited predisposition may also be an important factor in the susceptibility to lung carcinoma. Objective  To investigate the contribution of genetic factors to the risk of developing lung carcinoma in the Icelandic population. Design, Setting, and Participants  Risk ratios (RRs) of lung carcinoma for first-, second-, and third-degree relatives of patients with lung carcinoma were estimated by linking records from the Icelandic Cancer Registry (ICR) of all 2756 patients diagnosed with lung carcinoma within the Icelandic population from January 1, 1955, to February 28, 2002, with an extensive genealogical database containing all living Icelanders and most of their ancestors since the settlement of Iceland. The RR for smoking was similarly estimated using a random population-based cohort of 10 541 smokers from the Reykjavik Heart Study who had smoked for more than 10 years. Of these smokers, 562 developed lung cancer based on the patients with lung cancer list from the ICR. Main Outcome Measures  Estimation of RRs of close and distant relatives of patients with lung carcinoma and comparison with RRs for close and distant relatives of smokers. Results  A familial factor for lung carcinoma was shown to extend beyond the nuclear family, as evidenced by significantly increased RR for first-degree relatives (for parents: RR, 2.69; 95% confidence interval [CI], 2.20-3.23; for siblings: RR, 2.02; 95% CI, 1.77-2.23; and for children: RR, 1.96; 95% CI, 1.53-2.39), second-degree relatives (for uncles/aunts: RR, 1.34; 95% CI, 1.15-1.49; and for nephews/nieces: RR, 1.28; 95% CI, 1.10-1.43), and third-degree relatives (for cousins: RR, 1.14; 95% CI, 1.05-1.22) of patients with lung carcinoma. This effect was stronger for relatives of patients with early-onset disease (age at onset 60 years) (for parents: RR, 3.48; 95% CI, 1.83-8.21; for siblings: RR, 3.30; 95% CI, 2.19-4.58; and for children: RR, 2.84; 95% CI, 1.34-7.21). The hypothesis that this increased risk is solely due to the effects of smoking was rejected for all relationships, except cousins and spouses, with a single-sided test of the RRs for lung carcinoma vs RRs for smoking. Conclusions  These results underscore the importance of genetic predisposition in the development of lung carcinoma, with its strongest effect in patients with early-onset disease. However, tobacco smoke plays a dominant role in the pathogenesis of this disease, even among those individuals who are genetically predisposed to lung carcinoma.      

A population-based familial aggregation analysis indicates genetic contribution in a majority of renal cell carcinomas

The etiology of RCC is incompletely understood and the inherited genetic contribution uncertain. Although there are rare mendelian forms of RCC stemming from inherited mutations, most cases are thought to be sporadic. We sought to determine the extent of familial aggregation among Icelandic RCC patients in general. Medical and pathologic records for all patients diagnosed with RCC in Iceland between 1955 and 1999 were reviewed. This included a total of 1,078 RCC cases, 660 males and 418 females. With the use of an extensive computerized database containing genealogic information on 630,000 people in Iceland during the past 11 centuries, several analyses were conducted to determine whether the patients were more related to each other than members drawn at random from the population. Patients with RCC were significantly more related to each other than were subjects in matched groups of controls. This relatedness extended beyond the nuclear family. RRs were significantly greater than 1.0 for siblings, parents and cousins of probands. RRs were 2-3 for first-degree relatives and 1.6 for third-degree relatives. The risk of RCC is significantly higher for members of the extended family of an affected individual, as well as the nuclear family. Our results indicate that germline mutations are significantly involved in what has been defined as sporadic RCC.