Swedish National Cancer Registry Research Articles

Tattoos as a risk factor for malignant lymphoma: a population-based case–control study

The popularity of tattoos has increased dramatically over the last few decades. Tattoo ink often contains carcinogenic chemicals, e.g., primary aromatic amines, polycyclic aromatic hydrocarbons, and metals. The tattooing process invokes an immunologic response that causes translocation of tattoo ink from the injection site. Deposition of tattoo pigment in lymph nodes has been confirmed but the long-term health effects remain unexplored. We used Swedish National Authority Registers with full population coverage to investigate the association between tattoo exposure and overall malignant lymphoma as well as lymphoma subtypes. We performed a case-control study where we identified all incident cases of malignant lymphoma diagnosed between 2007 and 2017 in individuals aged 20-60 years in the Swedish National Cancer Register. Three random age- and sex-matched controls per case were sampled from the Total Population Register using incidence density sampling. We assessed exposure through a questionnaire in 2021, and data on potential confounders were retrieved from registers. We used multivariable logistic regression to estimate the incidence rate ratio (IRR) of malignant lymphoma in tattooed individuals. The study population consisted of 11,905 individuals, and the response rate was 54% among cases (n=1398) and 47% among controls (n=4193). The tattoo prevalence was 21% among cases and 18% among controls. Tattooed individuals had a higher adjusted risk of overall lymphoma (IRR=1.21; 95% CI 0.99-1.48). The risk of lymphoma was highest in individuals with less than two years between their first tattoo and the index year (IRR=1.81; 95% CI 1.03-3.20). The risk decreased with intermediate exposure duration (three to ten years) but increased again in individuals who received their first tattoo ≥11 years before the index year (IRR=1.19; 95% CI 0.94-1.50). We found no evidence of increasing risk with a larger area of total tattooed body surface. The risk associated with tattoo exposure seemed to be highest for diffuse large B-cell lymphoma (IRR 1.30; 95% CI 0.99-1.71) and follicular lymphoma (IRR 1.29; 95% CI 0.92-1.82). Our findings suggested that tattoo exposure was associated with an increased risk of malignant lymphoma. More epidemiologic research is urgently needed to establish causality. The Swedish Research Council for Health, Working Life and Welfare.

Breast Cancer Risk After Bariatric Surgery and Influence of Insulin Levels

Obesity and insulin are risk factors for breast cancer, and retrospective studies suggest bariatric surgery reduces breast cancer risk in women. However, long-term prospective data on breast cancer risk after bariatric surgery and the role of baseline insulin levels are lacking. To examine if bariatric surgery is associated with breast cancer incidence in women and if treatment benefit is modified by baseline insulin levels. The Swedish Obese Subjects (SOS) study was a nonrandomized intervention trial designed to investigate the long-term effects of bariatric surgery on obesity-related mortality and morbidity. Study recruitment took place between 1987 and 2001, and median (IQR) follow-up time was 23.9 years (20.1-27.1) years. The study was conducted at 25 public surgical departments and 480 primary health care centers in Sweden and included 2867 women aged 37 to 60 years and with body mass index 38 or greater (calculated as weight in kilograms divided by height in meters squared). In the surgery group (n = 1420), 260 women underwent gastric banding, 970 vertical banded gastroplasty, and 190 gastric bypass. The remaining contemporaneously matched control individuals (n = 1447) received usual obesity care. Breast cancer, the main outcome of this secondary report, was not a predefined outcome in the SOS study. Breast cancer events were identified in the Swedish National Cancer Registry. The study population comprised 2867 women with a mean (SD) age of 48.0 (6.2) years. During follow-up, there were 154 breast cancer events, 66 in the surgery group and 88 in the usual care group, and a decreased risk of breast cancer was observed in the bariatric surgery group (hazard ratio [HR], 0.68; 95% CI, 0.49-0.94; P = .019; adjusted HR, 0.72; 95% CI, 0.52-1.01; P = .06). The surgical treatment benefit on breast cancer risk was greater in women with baseline insulin levels above the median 15.8 μIU/L (HR, 0.48; 95% CI, 0.31-0.74; P = .001; adjusted HR, 0.55; 95% CI, 0.35-0.86; P = .008) compared to those below (HR, 0.95; 95% CI, 0.59-1.53; P = .84; adjusted HR, 1.01; 95% CI, 0.61-1.66; P = .97; interaction P = .02). This prospective clinical trial indicated a reduced risk of breast cancer after bariatric surgery in women with obesity. The surgical treatment benefit was predominantly seen in women with hyperinsulinemia. ClinicalTrials.gov Identifier: NCT01479452.

Warfarin intake in relation to diagnosis reduces mortality in patients with colorectal cancer – a register-based study

BackgroundSeveral studies have analyzed the effect of anticoagulants on cancer survival, with varying results. This study aimed to assess the effect of warfarin on survival in patients with colorectal cancer (CRC) in relation to timing of warfarin initiation. MethodsData on 10,051 individuals aged ≥45 years in the Västra Götaland Region of Sweden, and diagnosed with CRC between 2000 and 2009, were obtained from the Swedish National Cancer Register. Those who received warfarin treatment (n= 1,216) during the study period were labeled cases and those who did not (n= 8,873) were labeled controls. For statistical analysis, National Cancer Register data were merged with mortality data from the Swedish National Cause of Death register and data from the regional warfarin treatment register. ResultsHazard rates for CRC-specific mortality were lower in cases than in controls. When warfarin was used for any reason at any time, cases had a significantly lower CRC-specific mortality than controls among both women (hazard ratio [HR] 0.71; 95 % confidence interval [CI] 0.59–0.85; p= 0.0002) and men (HR 0.61; 95 % CI 0.52–0.72; p < 0001). Warfarin treatment after CRC diagnosis reduced CRC-specific mortality by 80 %; however, when warfarin was given before or ≥5 years after diagnosis, CRC-specific mortality did not significantly decrease. The number needed to treat to avoid one death was four. ConclusionUse of warfarin early after diagnosis in patients with CRC was associated with improved survival.

In situ breast cancer surgeries in Sweden: lumpectomy or mastectomy?—a cost-effectiveness analysis over a 30-Year period using Markov model

BackgroundBreast cancer represents the most prevalent cancer among Swedish women. Although considerable research has investigated the cost-effectiveness of emerging innovative medical treatments for breast cancer, studies addressing existing surgical procedures remain scant. Therefore, this study aimed to evaluate the cost-effectiveness of three surgical procedures for in situ breast cancer treatment in Sweden: mastectomy, lumpectomy without irradiation, and lumpectomy with irradiation.MethodsA six-state Markov model with a 30-year time horizon was used to compare the cost-effectiveness of the three alternatives. Transition probabilities were based on a targeted literature review focusing on available evidence in Sweden and comparable contexts. Costs were estimated from both healthcare and societal perspectives, using patient data from the Swedish National Cancer Registry in 2020 (Cancerregistret). Health outcomes were quantified in terms of quality-adjusted life years (QALYs). Cost and health outcomes were then summarised into an incremental cost-effectiveness ratio (ICER) between competing strategies. A probabilistic sensitivity analysis (PSA) was conducted to address the uncertainties in the input parameters.ResultsThe results showed that compared to lumpectomy without irradiation, lumpectomy with irradiation yielded a “moderate” ICER per QALY gained of 402,994 Swedish Krona (SEK) from a healthcare perspective and a “high” ICER of 575,833 SEK from a societal perspective. Mastectomy proved to be the costliest and least effective of the three alternatives over a 30-year period. The PSA results further substantiated these findings.ConclusionsOur study demonstrated that lumpectomy with irradiation is “moderately” cost-effective compared with lumpectomy without irradiation. Nevertheless, extending this study by conducting a comprehensive budget impact analysis to account for the prevalence of in situ breast cancer in Sweden is prudent. These results imply that a costlier and less effective mastectomy should only be considered when lumpectomy options are infeasible. Further studies are needed to obtain more reliable parameters relevant to Sweden and to increase the consistency of the findings.

Disinfection by-products in drinking water and risk of colorectal cancer: a population-based cohort study.

Colorectal cancer is the third most common malignancy worldwide and is strongly linked to lifestyle and environmental risk factors. Although several drinking-water disinfection by-products are confirmed rodent carcinogens, the evidence in humans for carcinogenicity associated with these by-products, including colorectal cancer, is still inconclusive. We assessed the association of long-term exposure to trihalomethanes (THMs), the most prevalent disinfection by-products in chlorinated drinking water, with incidence of colorectal cancer in 58 672 men and women in 2 population-based cohorts. Exposure was assessed by combining long-term information of residential history with drinking water-monitoring data. Participants were categorized according to no exposure, low exposure (<15µg/L), and high exposure (≥15µg/L). Incident cases of colorectal cancer were ascertained by use of the Swedish National Cancer Register. During an average follow-up of 16.8years (988 144 person-years), 1913 cases of colorectal cancer were ascertained (1176 cases in men and 746 in women, respectively). High THM concentrations in drinking water (≥15 µg/L) were associated with increased risk of colorectal cancer in men (hazard ratio = 1.26, 95% confidence interval = 1.05-1.51) compared with no exposure. When subsites were assessed, the association was statistically significant for proximal colon cancer (hazard ratio = 1.59, 95% confidence interval = 1.11 to 2.27) but not for distal colon cancer or rectal cancer. In women, we observed overall no association of THMs with colorectal cancer. These results add further evidence that disinfection by-products in drinking water may be a possible risk factor for proximal colon cancer in men. This observation was made at THM concentrations lower than those in most previous studies.

Prevalence of Beckwith Wiedemann Syndrome and Risk of Embryonal Tumors in Children Born with Omphalocele

Aim of the studyChildren with omphalocele have an increased prevalence of Beckwith Wiedemann syndrome (BWS) and thus a suspected increased risk of developing embryonal tumors, e.g. Wilms tumor, hepatoblastoma, neuroblastoma and rhabdomyosarcoma. The aim of this study was to examine the prevalence of BWS and the risk of embryonal tumors amongst patients born with omphalocele. MethodsA population-based cohort was used, including all children born in Sweden 1/1 1997–31/12 2016. Patients with omphalocele were identified through the Swedish National Patient Register and the Swedish Medical Birth Register. For each case of omphalocele ten age and sex matched individuals unexposed for omphalocele were randomly selected for comparison. Data on BWS and embryonal tumors were collected from the Swedish National Patient Register and the Swedish National Cancer Register. Main resultsOut of 207 cases of omphalocele, 15 (7.2%) were diagnosed with BWS. None of the children with omphalocele had yet developed any kind of embryonal tumor (median follow-up time 8 years). None of the 2070 controls were diagnosed with BWS but 3 (0.1%) of them had developed embryonal tumors during a median follow-up time of 10 years. ConclusionsIn this study the prevalence of BWS amongst children born with omphalocele is in the lower range of previously reported figures. Also, the prevalence of embryonal tumors amongst children with BWS is lower than expected and the risk of embryonal tumors in children with omphalocele and BWS might not be as high as previously stated. This must be taken into consideration when counseling parents prenatally. Type of StudyNational register cohort study. Level of EvidenceII.

KRAS G12C Mutant Non–Small Cell Lung Cancer Linked to Female Sex and High Risk of CNS Metastasis: Population-based Demographics and Survival Data From the National Swedish Lung Cancer Registry

BackgroundReal-world data on demographics related to KRAS mutation subtypes are crucial as targeted drugs against the p.G12C variant have been approved. MethodWe identified 6183 NSCLC patients with reported NGS-based KRAS status in the Swedish national lung cancer registry between 2016 and 2019. Following exclusion of other targetable drivers, three cohorts were studied: KRAS-G12C (n = 848), KRAS-other (n = 1161), and driver negative KRAS-wild-type (wt) (n = 3349). ResultsThe prevalence of KRAS mutations and the p.G12C variant respectively was 38%/16% in adenocarcinoma, 28%/13% in NSCLC-NOS and 6%/2% in squamous cell carcinoma. Women were enriched in the KRAS-G12C (65%) and KRAS-other (59%) cohorts versus KRAS-wt (48%). A high proportion of KRAS-G12C patients in stage IV (28%) presented with CNS metastasis (vs. KRAS-other [19%] and KRAS-wt [18%]). No difference in survival between the mutation cohorts was seen in stage I-IIIA. In stage IV, median overall survival (mOS) from date of diagnosis was shorter for KRAS-G12C and KRAS-other (5.8 months/5.2 months) vs. KRAS wt (6.4 months). Women had better outcome in the stage IV cohorts, except in KRAS-G12C subgroup where mOS was similar between men and women. Notably, CNS metastasis did not impact survival in stage IV KRAS-G12C, but was associated with poorer survival, as expected, in KRAS-other and KRAS-wt. ConclusionThe KRAS p.G12C variant is a prevalent targetable driver in Sweden and significantly associated with female sex and presence of CNS metastasis. We show novel survival effects linked to KRAS p.G12C mutations in these subgroups with implications for clinical practice.

Hyaluronic Acid Spacer in Prostate Cancer Radiotherapy: Dosimetric Effects, Spacer Stability and Long-Term GI Toxicity and PRO in a Phase II-Study

<h3>Purpose/Objective(s)</h3> Rectal side effects are common after radiotherapy (RT) to the prostate. To reduce side effects, perirectal spacers to separate the prostate from the rectum, thereby reducing the rectal dose, may be beneficial. This study presents the impact of a hyaluronic acid (HA) perirectal spacer on the rectal dose, MRI evaluation of spacer thickness during RT and a five-year follow-up of patient-reported outcome (PRO) and gastrointestinal (GI) toxicity. <h3>Materials/Methods</h3> 81 patients (<75 years) with low- (T1c-T2 and Gleason ≤ 6 and PSA < 10) and intermediate-risk prostate cancer (PC) (T1c-T3a with 1 or 2 of the risk factors T2c-T3a or Gleason ≥ 7 or PSA ≥ 10) received transrectal injections with HA (Macrolane VRF 30, Q-Med/Galderma, Uppsala, Sweden) as a perirectal spacer in this phase II-study between 2010-2016. External beam RT, 78 Gy in 39 fractions, were given with 3DCRT or IMRT using fiducial markers as image guidance. MRI was performed before (MR0) and after HA injection (MR1), at the middle (MR2) and at the end of RT (MR3). GI toxicity was assessed up to five years according to the RTOG scale. PRO GI side effects were collected using The Swedish national prostate cancer registry (NPCR) and PCSS questionnaires. <h3>Results</h3> HA thickness was measured at the prostate base, middle and apex for 52 of 81 patients. Exclusion due to failed HA-injections (6), missing MRT or RT data (17), larger PTV margins (5) and other treatment (1). HA thickness and CTV-Rectum spaces in apex- and middle- position was decreasing from MR1 to MR2/MR3. No significant differences were found between MR2 and MR3. Overall, HA thickness in the middle position had the strongest significant correlation (Spearman's rho ρ= 0.70) to CTV-Rectum spacing. There was a significant decrease in the relative rectum volume that received 70.2 Gy (V90%) from MR0 (8.6 ±5.7 %) to MR1 (2.7± 4.1 %). There was a significant increase from MR1 to MR2 (6.0±9.0%) and no significant difference between MR2 and MR3 (5.7±7.9 %) in rectum V90%. All with significance p<0.05. At the end of RT 17 patients (25.8%) experienced grade 1 GI toxicity, and four patients (6.1%) grade 2. At six months the proportion of grade 2 and 3 GI toxicity was 3.2%, and 1.6%. After 18 months no grade ≥ 2 GI toxicity was observed. The estimated cumulative late grade ≥ 2 GI toxicity rate at 5 years was 4.8 %. PRO moderate or severe overall bowel problems at start RT, end of RT and 5 years were 0%, 17.6% and 12.2% with a mean score of 14.6 (scale 0–100; higher value refers to more symptoms/worse function) at 5 years. <h3>Conclusion</h3> After HA-spacer, the relative rectum volumes receiving 70.2 Gy (V90%) were significantly lower. V90% increased significantly from MR1 to MR2/MR3, but still a significant reduction from MR0. The 5-year cumulative risk of late GI toxicity grade >1 was low whereas 12 % reported moderate/severe GI-bothers in the PRO at 5 years.

Overall survival of individuals with metastatic cancer in Sweden: a nationwide study

AimsConsistent improvements for overall survival (OS) have been reported for individuals with metastatic cancer. Swedish population-based registers allow national coverage and long follow-up time. The aim of this study was to estimate and explore long-term OS of individuals diagnosed with metastatic cancer using Swedish nationwide health registers.MethodsIndividuals with metastatic breast (MBC), non-small cell lung (MNSCLC), ovary (MOC) or colorectal cancer (MCRC) or metastatic malignant melanoma (MMM) were identified in the Swedish national cancer register and national patient registers. Survival was estimated and stratified by available variables. Potential cure fractions were estimated using mixture cure models.ResultsIn total, approximately 69,000 individuals were identified. The most common cancers were MCRC (36.2%) and MNSCLC (29.5%). Men were more frequently diagnosed with MNSCLC, MCRC, and MMM compared to women. Except for MOC, about 50% of individuals were 70 years or older at diagnosis. Throughout the study period survival differed across cancers. The longest median OS was observed for individuals with MOC and MBC. At 10 years of follow-up, the survival curves flatten at a survival rate of approximately 10% for all cancers except MNSCLC. The youngest age groups had the longest median OS. Increased survival was also observed for individuals diagnosed in 2015 and 2018 compared to individuals diagnosed during earlier years. The estimated cure fractions were 4% for MBC, 1.5% for MNSCLC, 6.8% for MCRC, 8.6% for MOC and MMM.ConclusionsLong-term survival has been assessed across all indications except for NSCLC.. The findings may be relevant for healthcare planning to meet the needs of future patients and potential long-term survivors.

Risk of Cancer in Children of Parents Occupationally Exposed to Hydrocarbon Solvents and Engine Exhaust Fumes: A Register-Based Nested Case–Control Study from Sweden (1960–2015)

Background:It remains unclear whether parental occupational exposure to hydrocarbon solvents (HCS) or engine exhaust fumes (EEF) is associated with higher risks of cancer in the offspring.Objectives:Our aim was to estimate relative risks of childhood cancers associated with maternal or paternal exposure to aliphatic/alicyclic, aromatic, or chlorinated HCS or gasoline/diesel EEF.Methods:We conducted a case–control study in which individuals old, born 1960–2014, were identified from the Swedish National Cancer Register (1960–2015) at first cancer diagnosis and matched to population controls (1 case:25 controls) on birth year and sex. Maternal and paternal occupation around the child’s birth was retrieved for 9,653 cases and 172,194 controls and 12,521 cases and 274,434 controls, respectively, using information from six censuses and a nationwide register. Using the Swedish job-exposure matrix (SWEJEM), we assessed exposure to HCS and EEF (any or higher/lower). Odds ratios (ORs) and 95% confidence intervals (CIs) of 15 childhood cancer subtypes were estimated using conditional logistic regression models adjusted for several confounders.Results:Maternal exposure to aromatic HCS was associated with non-Hodgkin lymphoma (; 95% CI: 1.05, 2.58), aliphatic/alicyclic HCS with germ cell tumors (; 95% CI: 0.89, 2.59), and gasoline/diesel EEF with astrocytoma (; 95% CI: 1.04, 1.88), myeloid leukemia (; 95% CI: 0.84, 2.81), lymphomas (; 95% CI: 0.85, 3.02 for Hodgkin; ; 95% CI: 0.71, 2.91 for non-Hodgkin), and epithelial tumors (; 95% CI: 0.93, 2.44). Paternal exposure to gasoline EEF was associated with Hodgkin lymphoma (; 95% CI: 1.01, 1.44) and soft tissue sarcomas (; 95% CI: 1.00, 1.48). No notable difference was observed between higher and lower exposure.Discussion:Our findings suggest that occupational exposure to HCS or EEF, especially in the mother, may increase the risk of some childhood cancers. They add to the growing literature on adverse effects from HCS and EEF in the child, but replication of these associations in other populations is warranted. https://doi.org/10.1289/EHP11035

Nationwide trends and outcomes of neoadjuvant chemotherapy in pancreatic cancer – an analysis of the Swedish national pancreatic cancer registry

Objectives During the last decade, neoadjuvant therapy (NAT) for pancreatic cancer has become more frequent. Pathological response and overall survival are promising; however, various post-operative complications have been reported. Our primary aim was to compare the complication scenario of patients receiving NAT in borderline resectable and locally advanced disease with those who had upfront pancreatic surgery (UFS) for primarily resectable cancer. Methods From the Swedish National Pancreatic and Periampullary Cancer Registry, patients resected for pancreatic ductal adenocarcinoma (PDAC) between 2010 and 2018 were identified. Data on patient characteristics, neoadjuvant therapy, post-operative complications and survival were obtained. Comparisons between groups as well as survival analysis were performed. Results Within the total cohort of 13,948 patients, 1894 (median age 69 years, 51% men) were resected for PDAC. Among these, 112 (5.9%) patients received NAT followed by surgery. The patients who received NAT were younger (67 vs 70 years, p < .001), had a lower level of CA19-9 (47 vs 108, p = .001) and had to a larger extent vascular resection (58.9 vs 26.9%, p < .001) and total pancreatectomy performed (23.2 vs 9.1%, p < .001). No difference was found for major post-operative complications and there was no significant change in survival rate between the NAT and UFS groups (median 28 vs 26 months, p = .122). Conclusions When analyzing data from a national registry, no difference in post-operative complications was found between resected patients receiving UFS and NAT for PDAC. Also, the survival was equal between groups. NAT is a feasible treatment option for patients with potentially curable pancreatic cancer.

ELISA, protein immunoprecipitation and line blot assays for anti-TIF1-gamma autoantibody detection in cancer-associated dermatomyositis.

Anti-TIF1-gamma autoantibodies can be detected with immunoprecipitation (IP), line blot (LB) and ELISA. We compared assay performance in patients with DM and the potential of these assays to detect anti-TIF1-gamma positive cancer-associated DM (CADM). We included sera from 131 patients with DM followed at Karolinska University Hospital, Stockholm, Sweden and 82 healthy controls. Serum samples taken at DM diagnosis were tested for anti-TIF1-gamma autoantibodies with IP, two ELISAs (in-house and commercial) and LB. Cancer diagnosis and dates were obtained from the Swedish national cancer register. CADM was defined as a malignancy that developed within 3 years of DM diagnosis. Anti-TIF1-gamma autoantibodies were detected in 19/101 (18.8%), 15/113 (13.2%), 34/131 (26%) and 45/131 (34.4%) of the patients with IP, LB, in-house and commercial ELISA, respectively. The anti-TIF1-gamma results from the in-house ELISA were confirmed with IP in 93 of 101 (92%) cases, κ = 0.76, with a commercial ELISA in 110 of 131 (84%) cases, κ = 0.63, and with LB in 101 of 113 (89.3%) cases, κ = 0.67. Anti-TIF1-gamma results with IP were confirmed with LB in 85 of 92 (92.4%) cases, κ = 0.73. For detecting CADM, the anti-TIF1-gamma in-house ELISA had a sensitivity of 58% and specificity of 86%, the commercial ELISA had a sensitivity of 63% and specificity of 82%, IP had a sensitivity of 52% and specificity of 92%, LB had a sensitivity of 40% and specificity of 96%. The two anti-TIF1-gamma ELISA assays had advantages both for autoantibody detection and to identify anti-TIF1-gamma-positive CADM.

Association of Bariatric Surgery With Cancer Incidence in Patients With Obesity and Diabetes: Long-term Results From the Swedish Obese Subjects Study

Obesity and type 2 diabetes are associated with serious adverse health effects, including cancer. Although bariatric surgery has been shown to reduce cancer risk in patients with obesity, the effect of bariatric surgery on cancer risk in patients with obesity and diabetes is less studied. We therefore examined the long-term incidence of cancer after bariatric surgery and usual care in patients with obesity and diabetes in the matched prospective Swedish Obese Subjects (SOS) study. The SOS study examines long-term outcomes following bariatric surgery or usual care. The current analysis includes 701 patients with obesity and type 2 diabetes at baseline, 393 of whom underwent bariatric surgery and 308 who received conventional obesity treatment. Information on cancer events was obtained from the Swedish National Cancer Register. Median follow-up time was 21.3 years (interquartile range 17.6-24.8 years, maximum 30.7 years). During follow-up, the incidence rate for first-time cancer was 9.1 per 1,000 person-years (95% CI 7.2-11.5) in patients with obesity and diabetes treated with bariatric surgery and 14.1 per 1,000 person-years (95% CI 11.2-17.7) in patients treated with usual obesity care (adjusted hazard ratio 0.63 [95% CI 0.44-0.89], P = 0.008). Moreover, surgery was associated with reduced cancer incidence in women (0.58 [0.38-0.90], P = 0.016), although the sex-treatment interaction was nonsignificant (P = 0.630). In addition, diabetes remission at the 10-year follow-up was associated with reduced cancer incidence (0.40 [0.22-0.74], P = 0.003). These results suggest that bariatric surgery prevents cancer in patients with obesity and diabetes and that durable diabetes remission is associated with reduced cancer risk.

Association of Inflammatory Markers and Blood Cell Counts and the Risk of Leukemia in the Swedish Amoris Cohort

Background: The presence of myeloid-derived inflammation is associated with different malignancies, including Leukemia. Certain risk factors (i.e., age, exposure to carcinogens including chemical and radiation), common gene mutations (such as the BCR-ABL fusion gene), and inflammatory markers (such as C-reactive protein (CRP)) have been associated with the risk of developing Leukemia, however cost-effective and widely acceptable predictor markers are not yet available. This study aimed to investigate the association of standard laboratory inflammatory biomarkers and blood cell counts and the long-term risk of Leukemia in a cohort of healthy individuals.Methods: Individuals from the Swedish Apolipoprotein Risk Study (AMORIS) cohort (n=124609, Male 56.7% vs. Female 43.3 ,>20 years of age) with baseline measurements of C-reactive protein (CRP), albumin, haptoglobin, white blood cell count, mean corpuscular volume (MCV) and platelets were included in the study. Multivariable cox proportional hazard regression analysis adjusted for age, sex, comorbidities (CCI), and socioeconomic status was performed to assess the association of the biomarkers and leukemia diagnosis (ICD-7 (204) Swedish National Cancer Register linkage). Individuals with a leukemia diagnosis within a year of the blood measurement were excluded to account for reverse causation. Considering the time of diagnosis and version of ICD, which was used, it was not possible to stratify patients based on current leukemia classification, including myeloid/ lymphoid or acute/ chronic.Results: A total of 218 participants (0.2%) developed leukemia over a median follow-up time of 17.54 years. Albumin (leukemia free mean=43.23 vs leukemia mean=42.90 (g/l); p<.001) WBC (leukemia free mean=6.62 vs leukemia mean=9.71 (WBC*×10 9/L); p<.001) and platelets (leukemia free mean=257.00 vs leukemia mean=248.99 (Platelets×10 9/L); p<.001) were all statistically significantly associated with risk of leukemia. When analyzing continuous values, the Hazard Ratio (HR) of albumin was: 1.04 (95%Confidence Interval (CI): 0.98-1.09); the HR of WBC was: 1.09 (95%CI 1.08-1.10) and HR for platelets was: 0.99 (95%CI 0.99-1.00). The analyses of the quartiles presented similar trends, albumin (HR Q4 vs Q1: 1.45 (95%CI 0.90-2.32);HR Q3 vs Q1: 1.62 (95%CI 1.04-2.52); HR Q2 vs Q1: 1.80 (95%CI 1.17-2.78)) (p for trend= 0.006), WBC (HR Q4 vs Q1: 3.57 (95%CI 2.38-5.36) ;HR Q3 vs Q1: 1.50 (95%CI 0.96-2.37); HR Q2 vs Q1: 0.84 (95%CI 0.51-1.40)) (p for trend= 0.08) and platelets (HR Q4 vs Q1: 0.77 (95%CI 0.54-1.11) ;HR Q3 vs Q1: 0.63(95%CI 0.43-0.92); HR Q2 vs Q1: 0.58 (95%CI: 0.40-0.86)) (p for trend =0.003).Conclusion: The present study presented a positive association between increasing albumin levels and high numbers of WBC and risk of Leukemia, while a negative association was found with high platelet counts, which highlight these markers as potential markers of long-term risk of Leukemia. The potential clinical use of these markers in the early detection of leukemia needs to be evaluated in further studies. DisclosuresKordasti: Alexion: Honoraria; Beckman Coulter: Honoraria; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding.

Short- and longer-term cancer risks with biologic and targeted synthetic disease-modifying antirheumatic drugs as used against rheumatoid arthritis in clinical practice.

ObjectiveTo estimate the occurrence and relative risks of first-ever-incident non-cutaneous cancer overall and for 16 sites in patients with RA treated with biologic and targeted synthetic DMARDs (b/tsDMARDs), by time since treatment start, attained age, and duration of active treatment.MethodsThis is an observational nationwide and population-based cohort study of patients with RA (n = 69 308), treated with TNF inhibitors (TNFi; adalimumab, certolizumab, etanercept, golimumab, infliximab) or other b/tsDMARDs (abatacept, rituximab, baricitinib, tofacitinib and tocilizumab) compared with RA patients not treated with b/tsDMARDs, and matched general population referents (n = 109 532), 2001–2018. The study was based on prospectively collected data from the Swedish Rheumatology Quality Register and from other registers, linked to the national Swedish Cancer Register. Incidence rates and hazard ratios were estimated via Cox regression adjusted for co-morbidities and other health characteristics.ResultsBased on 8633 incident cancers among RA patients, the overall relative risk of cancer with TNFi [hazard ratio (HR) = 1.0] was neither increased nor did it change with time since treatment start, duration of active treatment, or attained age, when compared with b/tsDMARD-naïve RA. For other b/tsDMARDs, we noted no consistent signal of increased overall risks (HRs ranged from 1.0 to 1.2), but there were statistically significant estimates above 1 for abatacept with 2–5 years of active treatment, for older age groups, and between several of the bDMARDs and urinary tract cancer.ConclusionTNFis, as used long term in clinical practice against RA, are not linked to increased risks for cancer overall. For other b/tsDMARDs, and for site-specific risks, our results are generally reassuring but contain signals that call for replication.

Periodontal microorganisms and diagnosis of malignancy: A cross-sectional study.

Oral infections associate statistically with cancer. We hypothesized that certain periodontal microorganisms might specifically link to malignancies in general and set out to investigate this in our ongoing cohort study. A sample of 99 clinically examined patients from our cohort of 1676 subjects was used to statistically investigate the associations between harboring periodontal microorganisms Aggregatibacter actinomycetemcomitans (A.a), Porphyromonas gingivalis (P.g), Prevotella intermedia (P.i), Tannerella forsythia (T.f) and Treponema denticola (T.d). We used oral infection indexes and the incidence figures of malignancies as registered in 2008-2016 in the Swedish National Cancer Register. The pathogen A.a showed strong association with malignancy in 32 out of the 99 patients while P.g and P.i were more prevalent among patients without malignancy. In principal component analyses, A.a appeared in the strongest component while the second strongest component consisted of a combination of T.f and T.d. The third component consisted of a combination of P.g and P.i, respectively. Of basic and oral health variables, gingival index appeared to be the strongest expression of inflammation (Eigen value 4.11 and Explained Variance 68.44 percent). The results partly confirmed our hypothesis by showing that harboring certain periodontal bacteria might link to malignancy. However, the associations are statistical and no conclusions can be drawn about causality.

Long-term incidence of colorectal cancer after bariatric surgery or usual care in the Swedish Obese Subjects study.

Bariatric surgery in patients with obesity is generally considered to reduce cancer risk in patients with obesity. However, for colorectal cancer some studies report an increased risk with bariatric surgery, whereas others report a decreased risk. These conflicting results demonstrate the need of more long-term studies analyzing the effect of bariatric surgery on colorectal cancer risk. Therefore, data from the Swedish Obese Subjects (SOS) study, ClinicalTrials.gov identifier: NCT01479452, was used to examine the impact of bariatric surgery on long-term incidence of colorectal cancer. The SOS study includes 2007 patients who underwent bariatric surgery and 2040 contemporaneously matched controls who received conventional obesity treatment. Patients in the surgery group underwent gastric bypass (n = 266), banding (n = 376) or vertical banded gastroplasty (n = 1365). Information on colorectal cancer events was obtained from the Swedish National Cancer Registry. Median follow-up was 22.2 years (inter-quartile range 18.3–25.2). During follow up there were 58 colorectal cancer events in the surgery group and 67 colorectal cancer events in the matched control group with a hazard ratio (HR) of 0.79 (95% CI:0.55–1.12; p = 0.183). After adjusting for age, body mass index, alcohol intake, smoking status, and diabetes, the adjusted HR was 0.89 (95% CI:0.62–1.29; p = 0.551). When analyzing rectal cancer events separately- 19 events in the surgery group and 31 events in the control group-a decreased risk of rectal cancer with surgery was observed (HR = 0.56; 95% CI:0.32–0.99; p = 0.045, adjusted HR = 0.61 (95% CI:0.34–1.10; p = 0.099), while the risk of colon cancer was unchanged. To conclude- in this long-term, prospective study, bariatric surgery was not associated with altered colorectal cancer risk.

The overall risk of malignancies is not increased in patients with Hirschsprung disease

PurposeHirschsprung disease (HSCR) has previously been associated with increased risk of medullary thyroid cancer. The aim of this study was to assess the overall risk of malignancies in patients with Hirschsprung disease in a population-based cohort.MethodsThis was a nationwide, population-based cohort study. The study exposure was HSCR and the study outcome was malignancy. The cohort included all individuals with HSCR registered in the Swedish National Patient Register between 1964 and 2013 and ten age- and sex-matched controls per patient, randomly selected from the Population Register. Data were linked with the Swedish National Cancer Register to identify individuals with malignancy diagnosis.ResultsThe cohort comprised 739 individuals with HSCR (565 male) and 7390 controls (5650 male). Median age of the cohort was 19 years (range 2–49). In total nine (1.2%) individuals in the exposed cohort were diagnosed with malignancies compared to 57 (0.8%) in the non-exposed cohort (p = 0.195). Median age at malignancy diagnosis was 3 years (range 0–46) in the exposed group, compared to 23 (range 0–42), p = 0.132. No cases with medullary carcinoma of the thyroid were found in this cohort.ConclusionsThere was no significant difference in risk of malignancies in the exposed group compared to the unexposed group.

No increased risk of relapse of breast cancer for women who give birth after assisted conception.

STUDY QUESTIONIs childbirth after IVF associated with a risk of relapse in breast cancer?SUMMARY ANSWERWomen who had been diagnosed with breast cancer and completed treatment had no increased risk of relapse if they gave birth after conceiving with IVF.WHAT IS KNOWN ALREADYPregnancy and childbirth have not been shown to increase the risk of relapse in breast cancer. Ovarian stimulation during IVF increases the oestrogen levels and could theoretically increase the risk of relapse in breast cancer.STUDY DESIGN, SIZE, DURATIONThis is a retrospective register study, using national Swedish register data from the National Patient Register, the Medical Birth Register, the Swedish National Cancer Register, the National Breast Cancer Register, the National Quality Registry of Assisted Reproduction (Q-IVF), the National IVF Dataset, the Swedish Prescribed Drug Register and the Cause of Death Register. All women diagnosed with breast cancer who were between 20 and 44 years of age during the years 1982 to 2014 and identified in the cancer registries were assessed.PARTICIPANTS/MATERIALS, SETTING, METHODSWomen, previously diagnosed with breast cancer, who had given birth after IVF (29 after completed breast cancer treatment and 8 after fertility preservation) were compared with a matched control group who had given birth after spontaneous conception. Matching was done in a ratio 1:4, based on T-stage (size of the tumour) and year of diagnosis +/−5 years.MAIN RESULTS AND THE ROLE OF CHANCEWe found 26 114 women that had been diagnosed with breast cancer when 20–44 years old and of those 860 had subsequently given birth, 823 after spontaneous and 37 after IVF conception. Follow-up time was similar between the groups, ranging from 2.6 to 24.0 years, with a mean follow-up time of 10.3 (SD 4.2) years in the IVF group and 10.7 (SD 4.4) years in the control group. There were no relapses (0/37) in the IVF group. The relapse rate for the matched controls was 36/148 (24.8%). Ten women who suffered relapse died due to breast cancer.LIMITATIONS, REASONS FOR CAUTIONThis is reassuring data; however, the result is based on a few cases. The poor coverage of important prognostic variables in the register resulted in uncertain comparability of the groups. The main limitation in this study is the extent of missing data on tumour-related variables, due to poor coverage from the early years of the National Breast Cancer Register. It is possible that the women accepted for IVF had a less aggressive breast cancer and were generally healthier than women delivering after conceiving spontaneously and therefore had a lower risk of relapse. Other limitations are the lack of information on the anticancer therapies used and type of disease relapse, plus the older of the two IVF registers did not hold information on unsuccessful IVF cycles, leaving only cycles leading to birth, to be analysed.WIDER IMPLICATIONS OF THE FINDINGSWe found no indication that women who had been diagnosed with breast cancer had an increased risk of relapse if they gave birth after conceiving with IVF. Based on our findings, there is no evidence to advise against IVF treatment in this group of women. More detailed registry data would be valuable for future studies, enabling proper matching of tumour characteristics between groups.STUDY FUNDING/COMPETING INTEREST(S)The study was financed by grants from the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (ALFGBG-720291), The Assar Gabrielsson Fund (FB 15-20), The Breast Cancer Fund and the Swedish Association of Local Authorities and Regions, SKL. There are no conflicts of interest to declare.

Association of Bariatric Surgery With Skin Cancer Incidence in Adults With Obesity

Obesity is a cancer risk factor, and bariatric surgery in patients with obesity is associated with reduced cancer risk. However, evidence of an association among obesity, bariatric surgery, and skin cancer, including melanoma, is limited. To investigate the association of bariatric surgery with skin cancer (squamous cell carcinoma and melanoma) and melanoma incidence. This nonrandomized controlled trial, the Swedish Obese Subjects (SOS) study, is ongoing at 25 surgical departments and 480 primary health care centers in Sweden and was designed to examine outcomes after bariatric surgery. The study included 2007 patients with obesity who underwent bariatric surgery and 2040 contemporaneously matched controls who received conventional obesity treatment. Patients were enrolled between September 1, 1987, and January 31, 2001. Data analysis was performed from June 29, 2018, to November 22, 2018. Patients in the surgery group underwent gastric bypass (n = 266), banding (n = 376), or vertical banded gastroplasty (n = 1365). The control group (n = 2040) received the customary treatment for obesity at their primary health care centers. The SOS study was cross-linked to the Swedish National Cancer Registry, the Cause of Death Registry, and the Registry of the Total Population for data on cancer incidence, death, and emigration. The study included 4047 participants (mean [SD] age, 47.9 [6.1] years; 2867 [70.8%] female). Information on cancer events was available for 4042 patients. The study found that bariatric surgery was associated with a markedly reduced risk of melanoma (adjusted subhazard ratio, 0.43; 95% CI, 0.21-0.87; P = .02; median follow-up, 18.1 years) and risk of skin cancer in general (adjusted subhazard ratio, 0.59; 95% CI, 0.35-0.99; P = .047). The skin cancer risk reduction was not associated with baseline body mass index or weight; insulin, glucose, lipid, and creatinine levels; diabetes; blood pressure; alcohol intake; or smoking. The results of this study suggest that bariatric surgery in individuals with obesity is associated with a reduced risk of skin cancer, including melanoma. ClinicalTrials.gov identifier: NCT01479452.