Showing papers by "Olof Nyrén published in 2006"

Obesity and Risk for Chronic Renal Failure

Abstract: Few large-scale epidemiologic studies have quantified the possible link between obesity and chronic renal failure (CRF) This study analyzed anthropometric data from a nationwide, population-based, case-control study of incident, moderately severe CRF Eligible as cases were all native Swedes who were aged 18 to 74 yr and had CRF and whose serum creatinine for the first time and permanently exceeded 34 mg/dl (men) or 28 mg/dl (women) during the study period A total of 926 case patients and 998 control subjects, randomly drawn from the study base, were enrolled Face-to-face interviews, supplemented with self-administered questionnaires, provided information about anthropometric measures and other lifestyle factors Logistic regression models with adjustments for several co-factors estimated the relative risk for CRF in relation to body mass index (BMI) Overweight (BMI>or=25 kg/m2) at age 20 was associated with a significant three-fold excess risk for CRF, relative to BMI or=30) among men and morbid obesity (BMI>or=35) among women anytime during lifetime was linked to three- to four-fold increases in risk The strongest association was with diabetic nephropathy, but two- to three-fold risk elevations were observed for all major subtypes of CRF Analyses that were confined to strata without hypertension or diabetes revealed a three-fold increased risk among patients who were overweight at age 20, whereas the two-fold observed risk elevation among those who had a highest lifetime BMI of >35 was statistically nonsignificant Obesity seems to be an important-and potentially preventable-risk factor for CRF Although hypertension and type 2 diabetes are important mediators, additional pathways also may exist

Meat intake and risk of stomach and esophageal adenocarcinoma within the European Prospective Investigation Into Cancer and Nutrition (EPIC).

Abstract: BACKGROUND: Dietary factors are thought to have an important role in gastric and esophageal carcinogenesis, but evidence from cohort studies for such a role is lacking. We examined the risks of gastric cancer and esophageal adenocarcinoma associated with meat consumption within the European Prospective Investigation Into Cancer and Nutrition (EPIC) cohort. METHODS: A total of 521,457 men and women aged 35-70 years in 10 European countries participated in the EPIC cohort. Dietary and lifestyle information was collected at recruitment. Cox proportional hazard models were used to examine associations between meat intake and risks of cardia and gastric non-cardia cancers and esophageal adenocarcinoma. Data from a calibration substudy were used to correct hazard ratios (HRs) and 95% confidence intervals (CIs) for diet measurement errors. In a nested case-control study, we examined interactions between Helicobacter pylori infection status (i.e., plasma H. pylori antibodies) and meat intakes. All statistical tests were two-sided. RESULTS: During a mean follow-up of 6.5 years, 330 gastric adenocarcinoma and 65 esophageal adenocarcinomas were diagnosed. Gastric non-cardia cancer risk was statistically significantly associated with intakes of total meat (calibrated HR per 100-g/day increase = 3.52; 95% CI = 1.96 to 6.34), red meat (calibrated HR per 50-g/day increase = 1.73; 95% CI = 1.03 to 2.88), and processed meat (calibrated HR per 50-g/day increase = 2.45; 95% CI = 1.43 to 4.21). The association between the risk of gastric non-cardia cancer and total meat intake was especially large in H. pylori-infected subjects (odds ratio per 100-g/day increase = 5.32; 95% CI = 2.10 to 13.4). Intakes of total, red, or processed meat were not associated with the risk of gastric cardia cancer. A positive but non-statistically significant association was observed between esophageal adenocarcinoma cancer risk and total and processed meat intake in the calibrated model. In this study population, the absolute risk of development of gastric adenocarcinoma within 10 years for a study subject aged 60 years was 0.26% for the lowest quartile of total meat intake and 0.33% for the highest quartile of total meat intake. CONCLUSION: Total, red, and processed meat intakes were associated with an increased risk of gastric non-cardia cancer, especially in H. pylori antibody-positive subjects, but not with cardia gastric cancer.

Risk Factors for Long-term Pain After Hernia Surgery

Abstract: Until recently, research on the results of hernia surgery has focused mainly on recurrences. However, with the introduction of mesh techniques and presumably an increased awareness of the importance of systematic quality control, the recurrence rate has decreased dramatically.1 Hence, now that recurrences are no longer a pressing clinical problem, there has been a recent upsurge in interest in chronic pain as an adverse outcome. But the level of quantification of pain has often been limited in studies addressing the risk of long-term pain, and pain has sometimes been treated merely as a dichotomous (yes/no) phenomenon.2 As a result, the clinical and public health significance of reported prevalence rates of residual pain (ranging between 0% and 37%) remains uncertain.3 With the main purpose of evaluating long-term pain as an alternative endpoint in research on the outcome of hernia surgery, we used a validated pain questionnaire to investigate pain behavior rather than imaginary descriptors of pain intensity in an essentially population-based series of patients operated on 59 hospitals.

The XPD 751Gln allele is associated with an increased risk for esophageal adenocarcinoma: a population-based case–control study in Sweden

Abstract: Mechanisms behind the strong associations of esophageal adenocarcinoma risk with gastroesophageal reflux (GOR) and body mass remain to be defined. In a nationwide population-based case-control study, we examined associations of polymorphisms in the DNA repair genes XPD, XPC, XRCC1 and XRCC3 with risk of esophageal adenocarcinoma, squamous-cell carcinoma (SCC) and gastric cardia adenocarcinoma, and paid special attention to possible interactions with symptomatic reflux or body mass. We collected blood samples from 96, 81 and 126 interviewed incident cases of esophageal adenocarcinoma, esophageal SCC and gastric cardia adenocarcinoma, respectively, and 472 randomly selected controls, frequency-matched with regard to age and sex. DNA was extracted and polymorphisms in XPD codon 751 (Lys-->Gln), codon 312 (Asp-->Asn), C insertion in intron 10 of XPD, XPC codon 939 (Lys-->Gln), XRCC1 codon 399 (Arg-->Gln) and XRCC3 codon 241 (Thr-->Met) were examined using PCR-RFLP. Odds ratios (ORs) derived from multivariate logistic regression with adjustments for potential confounding factors estimated relative risks. XPD codon 751 Lys/Gln and Gln/Gln genotypes, compared with Lys/Lys genotype, were both associated with a more than doubled risk for esophageal adenocarcinoma (OR=2.4; 95% CI=1.4-4.4; OR=2.7, 95% CI=1.3-5.9). The combined effects of these genotypes and symptomatic GOR or body mass showed borderline significant deviation from additivity. Excess risks for esophageal SCC were also noted for XPD 751Gln variant genotypes. Other studied variants were not found to be related to the three tumors. Our study suggests that XPD 751Gln allele is a potential genetic marker for susceptibility to esophageal adenocarcinoma.

A population‐based binational register for monitoring long‐term outcome and possible disease concordance among blood donors and recipients

Abstract: Background and Objectives Even with appropriate donor deferrals and advanced screening tests, the risk of disease transmission through blood transfusion cannot be completely disregarded. Efficient monitoring of possible disease transmission between blood donors and recipients should be an important component of a comprehensive haemovigilance system. Materials and Methods We assembled the Scandinavian Donations and Transfusions (SCANDAT) database, with data on virtually all blood donors and recipients who have been registered at least once in any of the computerized local blood bank databases in Sweden and Denmark since the start of computerized registration in 1966. The records of these individuals, with their entire computerized donation and/or transfusion histories and all donor-component-recipient connections, were linked to nationwide population and health registers to attain essentially complete follow-up for up to 36 years regarding reproduction, hospital morbidity, cancer, and death. Results After data cleaning, the database contained 1 134 290 blood donors who contributed 15 091 280 records of donations and 1 311 079 recipients who received 11 693 844 transfusions. The data quality in the existing data sources was satisfactory. From the data obtained from local blood banks, 4·6%, 1·6%, and 6·4% of the person, donation, and transfusion records, respectively, had to be discarded after review of the legitimacy of recorded values, and comparisons with independent, external databases. Conclusion It is possible to use existing computerized data, collected in routine health care, in haemovigilance systems for monitoring long-term outcome and disease concordance in blood donors and transfusion recipients.

Validity and reliability of self-reported total energy expenditure using a novel instrument.

Abstract: Improved methods for quantitative self-reports of total physical activity in epidemiological studies are needed. We evaluated randomly selected individuals' ability to integrate their perception of physical activity over time to produce an estimate of the "usual" level, using a novel instrument for self-quantification of energy expenditure. A population-based sample of 418 Swedish men and women, age 20-59, completed a questionnaire containing the new instrument. For validation, three 24 hour recalls by phone served as gold standard. Reproducibility was assessed through administering the instrument another three times. The validation involved 133 subjects and another 160 completed the reproducibility evaluation. Pearson correlation between usual daily energy expenditure measured by the instrument and the mean of the 24 hour recalls was 0.73. After subdividing the self-reported daily energy expenditure and the mean of the 24 hour recalls into quintiles, 83.5% of the participants remained in the same quintile, or one quintile apart. There was a tendency towards overestimation of usual daily physical activity. This was significantly associated with low education. Reproducibility showed an intraclass correlation of 0.55. Although integrated reports of usual daily energy expenditure over longer periods seem to be afflicted with a tendency of overestimation, total energy expenditure can be estimated with reasonable validity and reproducibility using our instrument.

Long-Term Cancer Risk Among Swedish Women With Cosmetic Breast Implants: An Update of a Nationwide Study

Abstract: Epidemiologic evidence does not support a consistently increased cancer risk among women with cosmetic breast implants, but few studies have assessed risk beyond 15 years. Swedish women who underwent cosmetic breast implantation for the first time between January 1, 1965, and December 31, 1993 (N = 3486), were followed through December 31, 2002. Cancer incidence was ascertained through the nationwide Swedish Cancer Registry. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated to compare cancer incidence of women with implants with women in the general population. Mean follow-up among women with breast implants was 18.4 years (range = 0.1-37.8 years). The incidence of breast cancer was below expectation (SIR = 0.7, 95% CI = 0.6 to 1.0), whereas lung cancer was above expectation (SIR = 2.2, 95% CI = 1.3 to 3.4). With respect to cancer overall and all other specific cancer sites, including brain cancer and sarcoma, non-Hodgkin lymphoma, and multiple myeloma, no statistically significantly increased or decreased SIRs were observed. Stratification by duration of follow-up revealed no statistically significantly increased or decreased SIR, with the exception of a two- to threefold excess of lung cancer among women followed for more than 15 years, which would be expected due to the high prevalence of smoking among the Swedish women with implants in our study.

A long-term follow-up study on the natural course of snus-induced lesions among Swedish snus users.

Abstract: Snus-induced lesions (SILs) are mucosal changes that are regularly seen in users of moist snuff (snus). Their role in oral carcinogenesis remains undefined. Our aim was to assess the natural course of SILs over several decades. A cohort of 1,115 individuals with SILs, confirmed in 1973-1974 during a population-based survey was followed for 27-29 years through multiple record linkages with virtually complete population- and health registers. A sample (n = 267) of the cohort members were invited for reexamination after 19-22 years. Register-based follow-up through January 2002 revealed a total of 3 incident cases of oral cancer (standardized incidence ratio of 2.3, 95% CI 0.5-6.7), none of which occurred at the site of the original SIL. There was a strong association noted between the degree of SIL and current snus consumption. The SILs had disappeared in all 62 individuals who had permanently quit using snus. In no case did we observe an important clinical change for the worse among individuals who had decreased their use or continued unabatedly. While the incidence of oral cancer in this cohort of individuals with SILs tended to be higher than expected, we conclude that cancers rarely occur at the site of lesions observed in the distant past.

A nationwide epidemiologic study of breast cancer incidence following breast reduction surgery in a large cohort of Swedish women

Abstract: While it has been demonstrated that prophylactic mastectomy reduces breast cancer incidence among women at high risk, many women often consider this disfiguring surgery unacceptable. One alternative approach may be breast reduction surgery. In order to evaluate the long-term incidence of breast cancer following surgical removal of breast tissue, we have extended by 9 years the follow-up period of our earlier retrospective cohort study of Swedish women electing cosmetic breast reduction surgery (n=30,444) between 1965 and 1993, yielding an average of nearly 16 years of follow-up. Cancer incidence through 2002 was ascertained via the Swedish Cancer Registry. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated comparing women who underwent breast reduction surgery with women in the general Swedish population. Breast cancer was observed in 443 women versus 624 expected for a statistically significant reduced SIR of 0.71 (95% CI=0.65–0.78). Analyses by age at surgery, time since surgery or calendar year of surgery revealed similar reductions in risk. Our study of over 30,000 women with long-term follow-up offers further evidence that women undergoing breast reduction surgery have reduced breast cancer risk. As the evidence from large-scale cohort studies accumulates, direct testing of this reduction in risk through clinical trials should be considered.

Elevated anal squamous cell carcinoma risk associated with benign inflammatory anal lesions

Abstract: Background: The association between benign anal lesions and anal cancer is still unclear. Few data from large cohort studies are available. Methods: We conducted a register based retrospective cohort study including 45 186 patients hospitalised for inflammatory anal lesions (anal fissures, fistulas, and perianal abscesses) as well as 79 808 haemorrhoid patients, from 1965 to 2002. Multiple record linkages identified all incident anal (squamous cell carcinoma only) and colorectal cancers through to 2002. Relative risk was estimated by standardised incidence ratio (SIR), the ratio of observed number of cases divided by that expected in the age, sex, and calendar year-matched general Swedish population. Results: There was a distinct incidence peak in the first three years of follow up among patients with inflammatory lesions. SIR then levelled off at around 3 and remained at this level throughout follow up (SIR during years 3–37 of follow up was 3.3 (95% confidence interval 1.8–5.7)). A similar initial incidence peak was observed among haemorrhoid patients but was confined to the first year; SIR was 2.8 in the second year, and then it decreased further and was close to unity in the following years (SIR during years 3–37 was 1.3 (95% confidence interval 0.7–2.1)). Among inflammatory lesion and haemorrhoid patients, a significantly increased risk of colorectal cancer was observed only in the first year after hospitalisation. Conclusions: Inflammatory benign anal lesions are associated with a significantly increased long term risk of anal cancer. In contrast, haemorrhoids appear not to be a risk factor for this malignancy.

On the natural course of oral lichen lesions in a Swedish population-based sample.

Abstract: MaxillofacialUnit, Halmstad Hospital, Halmstad, SwedenOBJECTIVES: The aim was to assess the natural courseof oral lichen lesions (OLL) among unselected, non-con-sulting individuals.SUBJECTS AND METHODS: A cohort of 327 subjectswith OLL, confirmed in 1973–1974 during a population-based survey in two Swedish municipalities, was followedthrough January 2002 via record linkages with nationwideand essentially complete registers. A sample of 80 drawnfrom the 194 surviving subjects who still resided in thearea in 1993–1995 was invited for interview and oral re-examination.RESULTS: At the end of follow-up, one case of oral can-cer was detected, while 0.4 were expected. The overallmortality among subjects with OLL was not significantlydifferent from that in the 15 817 OLL-free subjects whoparticipated in the initial population based survey in1973–1974. The lesion had disappeared in 14 (39%) of 36re-examined subjects with white OLLs in 1973–1974, andfour (11%) had transformed into red types. In the cor-responding group of 19 with red forms initially, five (26%)had become lesion free and four (21%) had switched towhite types. Although the cohort size does not permitfirm conclusions regarding oral cancer risk, the naturalcourse over up to 30 years appears to be benign in thegreat majority.J Oral Pathol Med (2006) 35: 257–61Keywords: lichenoid; epidemiology; oral mucosa; cancer; lichenplanus; oral

Helicobacter pylori Infection: Mainly Foe but Also Friend?

Abstract: Journal of the National Cancer Institute, Vol. 98, No. 20, October 18, 2006 The discovery of Helicobacter pylori revolutionized peptic ulcer treatment and justifi ably led to the awarding of last year’s Nobel Prize to Robin Warren and Barry Marshall. H. pylori eradication therapy is associated with threeto fi vefold higher success rates in preventing duodenal and gastric ulcer recurrences compared with placebo and is superior to pharmacologic acid suppression in duodenal ulcer healing ( 1 ) . Consequently, elimination of H. pylori infection in peptic ulcer patients is by no means controversial. During the past 15 years, numerous observational studies of various designs have also demonstrated a positive association between the presence of anti – H. pylori antibodies and the risk of stomach cancer. The literature on this association has become so extensive that the fi rst review of published meta-analyses is now available ( 2 ) . Each of the six meta-analyses included in that review showed that serologic evidence of H. pylori infection is associated with increased stomach cancer risk, with pooled odds ratios (ORs) of stomach cancer that ranged from 1.92 to 2.56 and with little heterogeneity. In other words, individuals who carry antibodies to H. pylori purportedly have a two to three times higher risk of stomach cancer than people who do not carry such antibodies. Some of the more recent studies, however, have reported a stronger association when the outcome was restricted to noncardia gastric cancer and when measures were taken to deal with the fairly frequent occurrence of “ false-negative ” tests for H. pylori antibodies resulting from the infection’s tendency to disappear from the precancerous or cancerous stomach without leaving behind any measurable antibodies. One of the reviewed meta-analyses also indicated that the risk of stomach cancer varies according to the type of H. pylori strain a person is infected with ( 3 ) . Approximately 60% of all H. pylori strains isolated in Western countries have the cagA gene, which is located in a variable 40-kb locus (termed the cag pathogenecity island). Strains that carry this locus (cagA-positive strains) are particularly virulent and have consistently been found to be more strongly linked to stomach cancer than cagA-negative strains. It has been shown that some patients with noncardia stomach cancer have antibodies to the CagA protein but no H. pylori anti bodies according to conventional immunoglobulin G (IgG) enzymelinked immunosorbent assay (ELISA) serologic tests based on mixed surface antigens from whole cell preparations and that the use of a broader criterion of H. pylori seropositivity that involves evidence of either mixed surface antibodies or antibodies to CagA dramatically increased the strength of the observed association between the infection and noncardia gastric cancer in case – control study settings ( 4 ) . Antibodies against CagA seem to persist in serum for longer times after H. pylori eradication than antibodies to the mixed surface antigens captured by conventional IgG ELISA ( 5 ) and are thus more likely to signal burnedout infections from the past. The stronger association with stomach cancer typically observed when seropositivity to CagA Affi liations of authors: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (ON); International Epidemiology Institute, Rockville, MD (WJB); Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (WJB ). Correspondence to: Olof Nyrén, MD, PhD, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Box 281, SE-171 77 Stockholm, Sweden (e-mail: olof.nyren@ki.se ).

Perinatal Risk Factors for Cancer of the Esophagus and Gastric Cardia: A Nested Case-Control Study

Abstract: Background: We have previously hypothesized that preterm birth or impaired fetal growth may cause esophageal adenocarcinomas through gastroesophageal reflux early in life. In this study, we aimed to test if there is an association between gestational duration and birth weight on the one hand, and risk of esophageal and cardia adenocarcinoma on the other. Methods: We conducted a nested case-control study of 67 cases of esophageal adenocarcinoma and 93 cases of cardia adenocarcinoma, whereas 50 cases of squamous cell carcinoma were studied for comparison. Birth records of cases were traced. Three matched controls per case were randomly selected. Perinatal data were extracted from birth records. Results: Long gestational duration was associated with a decreased risk of cardia adenocarcinoma ( P trend = 0.001) and a nonsignificant decreased risk of esophageal adenocarcinoma ( P = 0.07), whereas no such association was found for esophageal squamous cell carcinoma ( P = 0.96). Birth weight was not associated with risk of any of the studied cancers. Compared with lower maternal age (≤24 years) at giving birth, maternal age of 25 to 29 years were associated with a decreased risk of esophageal adenocarcinoma and squamous cell carcinoma (odds ratio, 0.4; 95% confidence interval, 0.2-0.9 and odds ratio, 0.3; 95% confidence interval, 0.1-0.8, respectively). Conclusions: Numerical constraints hamper inference, but our results are somewhat consistent with the idea that future risk of esophageal and cardia cancer may in part be determined already perinatally or in infancy and give some limited support to the hypothesis that timing of birth influences risk. (Cancer Epidemiol Biomarkers Prev 2006;15(5):867–71)

Antibiotic treatment and risk of gastric cancer

Abstract: Background/aims: Helicobacter pylori infection is undoubtedly an important risk factor for gastric cancer. It remains unclear however whether antibiotic treatment may prevent gastric cancer development. Our aim was to assess long term gastric cancer risks in historic cohorts of patients presumed to have been heavily exposed to antibiotics. Subjects: Using the Swedish Inpatient Register, we identified 501 757 individuals discharged with any one of 10 selected infectious disease diagnoses between 1970 and 2003. Methods: We counted person time and non-cardia gastric cancer occurrences through linkage to virtually complete population and health care registers. Standardised incidence ratios (SIRs) were calculated for comparisons with cancer incidence rates of the general population in Sweden. Results: No reduction in gastric cancer risk was observed in the infectious disease cohort in total (SIR 1.08 (95% confidence intervals 1.00–1.17) or for any of the presumed antibiotic regimens. There were no clear trends towards decreasing risk with time of follow up, but the risk tended to fall with increasing age at first hospitalisation for the infection (p Conclusions: Our results do not confirm earlier observational findings of a reduced risk of gastric cancer following exposure to heavy antibiotic treatment among hip replacement patients. Suboptimal drug regimens, inadequate timing of H pylori eradication, or insufficient follow up time may possibly explain the lack of association in this setting. Although our findings do not rule out the cancer preventive potential of H pylori eradication, they emphasise that detection of such an effect, if any, may require considerable efforts.