1.
Frank, Christoph, et al.
(author)
The population impact of familial cancer, a major cause of cancer
2014
In: International Journal of Cancer. - : Wiley. - 0020-7136. ; 134:8, s. 906-1899
Journal article (peer-reviewed) abstract
The population attributable fraction (PAF) defines the proportion of a disease that would be prevented if the exposure to a particular risk factor was avoided. Familial risk is a known risk factor for many cancers, but an unbiased estimation of the PAF for familial risk requires a large study population to include rare cancers. PAFs and their corresponding standardized incidence ratios (SIRs) were calculated for familial relative risk among first-degree relatives (FDRs) and second-degree relatives (SDRs) diagnosed with the same (concordant) invasive or in situ cancers. Calculations were based on the Swedish Family-Cancer Database considering 8,148,737 individuals. To assess environmental effects, PAFs were also calculated for concordant cancers among spouses. Almost all cancers showed a significant familial risk. The highest PAFs were found for the common cancers of the prostate (13.94%), breast (7.46%) and colorectum (6.78%) among the FDRs. In the FDRs, the overall PAF for any concordant cancer was 4.20%, but in the SDRs, it was only 0.34%. The overall PAFs for in situ cancers were 0.86% and 0.56% for the FDRs and SDRs, respectively. The overall independent familial PAF was 5.96% for the invasive and in situ cancers in the FDRs and SDRs. The cancers between spouses yielded an overall PAF of 0.14%. For esophageal cancer, the risk among spouses was higher than the familial risk. Our study shows that the overall familial PAF of 5.96%, although underestimated for sex-specific cancers, ranks as the third most common population burden after tobacco smoking and unhealthy diet.
2.
Riihimäki, Matias, et al.
(author)
Metastatic spread in patients with gastric cancer
2016
In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:32, s. 52307-52316
Journal article (peer-reviewed) abstract
Background: The epidemiology of metastatic gastric cancer is unexplored because cancer registries seldom cover metastatic involvement apart from "present or not". We used a novel approach by utilizing Swedish registers to assess metastatic spread in gastric cancer. To our knowledge, this is the first nationwide description of metastases in gastric cancer. Results: The most common sites of metastasis were liver (in 48% of metastatic cancer patients), peritoneum (32%), lung (15%), and bone (12%). Metastases to the lung, nervous system, and bone were more frequent in cardia cancer and men, whereas non-cardia cancer more frequently metastasized within the peritoneum. Signet ring adenocarcinomas more frequently metastasized within the peritoneum, bone and ovaries, and less frequently to the lungs and liver compared with generic adenocarcinoma. The liver and the peritoneum were commonly single metastases while lung metastases occurred frequently together with liver metastases. The median survival in metastatic gastric cancer was 3 months, worst among those with bone and liver metastases (2 months). Methods: A total of 7,559 patients with gastric cancer were identified. Metastatic patterns and survival depending on sex, age, stage, anatomical location (cardia and non-cardia), and histological type were assessed. Conclusions: The patterns of metastasis differ notably depending on histological type. Cardia cancer exhibits a completely different metastatic behavior than noncardia cancer. Awareness of the differing patterns may guide in tailored diagnosis of metastases. Survivors from cardia cancer would benefit from increased surveillance of extraperitoneal metastases. Bone metastases should be considered in patients with signet ring adenocarcinoma if symptoms emerge.
3.
Hemminki, Kari, et al.
(author)
Autoimmune diseases and hematological malignancies : exploring the underlying mechanisms from epidemiological evidence
2020
In: Seminars in Cancer Biology. - : Elsevier BV. - 1096-3650 .- 1044-579X. ; 64, s. 114-121
Research review (peer-reviewed) abstract
Autoimmune diseases are characterized by the irregular functioning of the immune system that leads to the loss of tolerance to self-antigens. The underlying nature of autoimmune diseases has led to speculation that the risk of malignancy might be higher or lower in patients with such diseases. However, the rarity and heterogeneity of both autoimmune diseases and malignancies is the main challenge for systematic exploration of associations between autoimmune diseases and cancer. The nationwide usages of electronic health records in Sweden and other countries has created longitudinal clinical datasets of large populations, which are ideal for quantifying the associations as well as possible guidance concerning the underlying mechanisms. In this report, we firstly summarize the population-based epidemiological association studies between autoimmune diseases and subsequent hematological malignancies using data derived mainly from Swedish nationwide data. These include over one million cancer cases and approximately 500,000 patients with medically diagnosed autoimmune disease. We further discuss the underlying mechanisms that contribute to the observed association between autoimmune diseases and hematological malignancies, including shared genetics, environmental factors, medical treatments of autoimmune diseases as well as dysregulated immune function.
4.
Chattopadhyay, Subhayan, et al.
(author)
Second primary cancers in non-Hodgkin lymphoma : Family history and survival
2020
In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 146:4, s. 970-976
Journal article (peer-reviewed) abstract
Second primary cancers (SPCs) account for an increasing proportion of all cancer diagnoses and family history of cancer may be a risk factor for SPCs. Using the Swedish Family-Cancer Database on non-Hodgkin lymphoma (NHL), we assessed the influence of family history on risk of SPCs and of SPCs on survival. NHL patients were identified from the years 1958 to 2015 and generalized Poisson models were used to calculate relative risks (RRs) for SPCs and familial SPCs. Among 14,393 NHL patients, a total of 1,866 (13.0%) were diagnosed with SPC. Familial risk of nine particular cancers was associated with risks of these cancers as SPCs, with twofold to fivefold increase in RRs. At the end of a 25-year follow-up period, the survival probability for persons with SPC was only 20% of that for patients without SPC; the hazard ratio for SPC was 1.59 (95% CI: 1.46–1.72). Survival could be predicted by the prognostic groups based on first cancers and HRs increase systematically with worse prognosis yielding a trend of p = 4.6 × 10 −5 . SPCs had deleterious consequences for survival in NHL patients. Family history was associated with increasing numbers of SPCs. Prevention of SPCs and their early detection is an important target in the overall strategy to improve survival in NHL patients. Counseling for avoidance of risk factors and targeted screening based on family history are feasible steps in risk reduction.
5.
Li, Xinjun, et al.
(author)
Familial Risks between Pernicious Anemia and Other Autoimmune Diseases in the Population of Sweden
2021
In: Autoimmune Diseases. - : Hindawi Limited. - 2090-0422 .- 2090-0430. ; 2021
Journal article (peer-reviewed) abstract
Background. Pernicious anemia (PA) is an autoimmune disease (AID) which is caused by lack of vitamin B12 (cobalamin) due to its impaired uptake. PA is a multifactorial disease which is associated with a number of other AID comorbidities and which is manifested as part of autoimmune polyglandular syndrome. Due to the shortage of family studies on PA, we planned to address the problem by assessing familial risks for concordant PA between family members and for discordant PA in families of other AID patients. Methods. We collected data on patients diagnosed with AIDs from the Swedish hospitals and family data from a population register. We calculated standardized incidence ratios (SIRs) in families for concordant and discordant risks. Results. The number of PA patients in the offspring generation (for which the familial risk was calculated) was 7701; 278 (3.6%) patients had a family history of PA. The population prevalence of PA was 0.9/1000. The familial risk for PA was 3.88 when any first-degree relative was the proband, equal for men and women. The familial risk was two times higher between siblings than between offspring and parents which may be due to complex genetic background. Associations of PA with 14 discordant AIDs were significant; these included some AIDs that have previously been described as comorbidities in PA patients and several yet unreported associations, including rheumatoid arthritis and other AIDs. Conclusions. The familial risks for PA were high suggesting multifactorial genetic etiology. The results call for further population-level studies to unravel mechanisms of familial PA which may help to understand the etiology of this disease.
6.
Zhang, Luyao, et al.
(author)
Familial Clustering, Second Primary Cancers and Causes of Death in Penile, Vulvar and Vaginal Cancers
2019
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
Journal article (peer-reviewed) abstract
Data on familial risks in penile and vulvar/vaginal cancers and in second primary cancers (SPCs) following these cancers are limited. We used the Swedish Family-Cancer Database from years 1958 through 2015 to identify 3641 penile and 8856 vulvar/vaginal cancers and to calculate relative risks (RRs) and 95% confidence intervals (CIs) for these cancers according to site-specific cancer in family members; additionally risk for SPCs was calculated. The familial RR for concordant (same) penile cancer was 3.22 (1.34–7.74), and it was 2.72 (1.69–4.39) for vulvar/vaginal cancer; RRs were increased for vulvar/vaginal cancer in families of anal cancer patients. RR for second penile cancer after penile cancers was 11.68 (7.95–17.18), while that for concordant vulvar/vaginal cancer was 9.03 (7.31–11.15). SPCs were diagnosed in 16.8% of penile cancer patients and in them 45.9% of deaths were caused by SPC (other than penile cancer). In vulvar/vaginal cancer patients with SPC, 36.4% of deaths were due to SPC. The results showed that these genital cancers might run in families and as SPCs are associated with human papilloma virus and smoking related cancers. Risk for these genital and anal SPCs are high and a follow-up plan should be agreed at diagnosis of these cancers.
7.
Zhang, Luyao, et al.
(author)
Second cancers and causes of death in patients with testicular cancer in Sweden
2019
In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:3
Journal article (peer-reviewed) abstract
While treatment for testicular cancer (TC) has become standardized after the 1980s with an associated significant improvement in patient survival, this has been accompanied by an increased risk of second primary cancers (SPCs). Patients were identified from the Swedish Cancer Registry spanning the years from 1980 to 2015, including 8788 individuals with primary TC and their SPCs. Relative risks (RRs) for SPC were calculated using the generalized Poisson regression model. SPCs were diagnosed in 9.4% of patients with TC and half of them were late onset cancers not common in the population in their 40s. Overall RR of SPCs (excluding second TC) was 1.30 (95%CI: 1.20–1.40), including high risks for seven solid cancers, non-Hodgkin lymphoma and leukemia. Second TC was the most common SPC and the RR of 17.19 (95%CI: 14.89–19.85) was the highest recorded. Cancers known to be fatal as first primary cancers were also fatal as SPC in TC patients. Survival at 30 years of follow-up was approximately 80% for TC patients without SPC but it decreased to 40% for patients with SPC. The unexpected finding that half of the identified SPCs were typical late onset cancers in the middle-aged population raises concerns that therapy may facilitate premature aging. The risks of SPC are clinically important for the long-term management of TC patients and the high-mortality calls for a future management strategy.
8.
Zheng, Guoqiao, et al.
(author)
Rate differences between first and second primary cancers may outline immune dysfunction as a key risk factor
2020
In: Cancer Medicine. - : Wiley. - 2045-7634. ; 9:21, s. 8258-8265
Journal article (peer-reviewed) abstract
Background: Many cancers are increased in immunosuppressed patients and evidence is accumulating that immune dysfunction may be a contributing risk factor for second primary cancers (SPCs). The aim of this study was to explore the potential influence of immune mechanisms in SPC. Methods: We used the Swedish Cancer Registry (1990-2015) to select 13 male and 14 female first primary cancers (FPCs) that are known to be related to immune suppression. We assessed relative risks (RRs) for any of these as concordant (same first and second cancer) and discordant FPC-SPC pairs. Hierarchical clustering of significant RRs was performed for cancers as FPC and SPC. Results: Concordant risks for SPCs were excessive in men and women for nasal (RRs 59.3 for men and 150.6 for women), tongue/mouth (51.7 and 100.8), and lip (32.4 and 61.2) cancers. Heatmaps showed that some cancers, such as skin cancer, tongue/mouth cancers, and non-Hodgkin lymphoma had multiple bidirectional associations as FPC and SPC. Nasal cancer and chronic lymphocytic leukemia had associations mainly as FPC while liver and kidney cancers showed most associations as SPC. Conclusions: Immune dysfunction may be a plausible contributing factor for most of the associations, which calls for experimental verification.
9.
Zheng, Guoqiao, et al.
(author)
Second Primary Cancers After Kidney Cancers, and Kidney Cancers as Second Primary Cancers
2021
In: European Urology Open Science. - : Elsevier BV. - 2666-1691 .- 2666-1683. ; 24, s. 52-59
Journal article (peer-reviewed) abstract
Background: Second primary cancers (SPCs) are increasing due to improving survival in first primary cancers. Previous studies on SPCs in renal cell carcinoma (RCC) have focused on treatment and other risk factors, but data of RCC as an SPC are scarce. Objective: In this study, we want to elucidate the risk for any SPC after RCC, and in reverse order, for RCC as an SPC after any cancer. We additionally consider how family histories influence the risks. Design, setting, and participants: Patient data were obtained from the Swedish Cancer Registry from years 1990 through 2015, and family data were obtained from the Multigeneration Register. Outcome measurements and statistical analysis: We employed standardized incidence ratios to estimate bidirectional relative risks of subsequent cancer associated with RCC. Results and limitations: We identified 17 587 RCCs (60% in male patients). The highest increases for SPCs were observed for nervous system hemangioblastoma (HB; 26.8), adrenal (12.09) tumors, and renal pelvic cancer (6.32). In the reverse order, RCC as an SPC, nervous system HB (17.01), and adrenal tumors (15.34) were associated with the highest risks. Risks for many other sites (12 sites and subsites) were increased bidirectionally. For women, a total of seven sites and subsites were increased bidirectionally, and many were shared with men. The only significant sex difference in SPCs was the higher lung cancer risk in women (2.41) than in men (1.28). Patients with a family history of HBs or of prostate, colorectal and lung cancers showed high risks of these cancers as SPCs after RCC. Family history accounted for 30% of prostate cancers after RCC. Conclusions: The bidirectional study design was able to suggest risk factors for SPCs and offered a clinical take-home message urging to consider strategies for early detection and prevention of SPCs. Readily available information on lifestyle (eg, smoking) and family history (eg, prostate cancer) may reveal targets for risk reduction with prognostic benefits. Patient summary: Close to 10% of kidney cancer patients develop another cancer. The cause for these other cancers may not depend on kidney cancer.
10.
