Effect of autoimmune diseases on mortality and survival in subsequent digestive tract cancers

BackgroundPatients with some autoimmune diseases (AIDs) are at increased risk of cancer, possibly a result of an underlying dysregulation of the immune system, medication, treatment or, probably, surveillance bias. Data on cancer mortality and survival in patients previously diagnosed with AIDs would provide novel information on these comorbidities and their clinical implications.Patients and methodsStandardized mortality ratios (SMRs) and hazard ratios (HRs) were calculated for subsequent deaths from seven digestive tract cancers between 1964 and 2008 in patients hospitalized for any of 33 AIDs.ResultsThere were 33 increased SMRs for specific cancers after a defined AID; similarly, 21 HRs were increased. Both the SMR and HR were increased after 10 autoimmune disorders, including pernicious anemia, systemic lupus erythematosus and psoriasis. Increased SMRs and unchanged HRs were noted for 23 cancers. Myasthenia gravis was associated with SMRs for five cancers but no increases in HRs. For nine cancers, including esophageal cancer after ulcerative colitis and rheumatoid arthritis, the SMR was unchanged but the HR increased.ConclusionsThe increases in SMRs provide evidence that cancer risks were truly increased and largely unaffected by surveillance bias. The prognostic survival data should contribute to clinical evaluation and therapeutic planning.     

Risk of cancer of unknown primary after hospitalization for autoimmune diseases

Cancer of unknown primary (CUP) is a heterogeneous syndrome diagnosed at metastatic sites. The etiology is unknown but immune dysfunction may be a contributing factor. Patients with autoimmune diseases were identified from the Swedish Hospital Discharge Register and linked to the Swedish Cancer Registry. Standardized incidence ratios (SIRs) were calculated for subsequent CUP and compared with subjects without autoimmune diseases. A total of 789,681 patients were hospitalized for any of 32 autoimmune diseases during years 1964–2012; 2,658 developed subsequent CUP, giving an overall SIR of 1.27. A total of 16 autoimmune diseases were associated with an increased risk for CUP; polymyositis/dermatomyositis showed the highest SIR of 3.51, followed by primary biliary cirrhosis (1.81) and Addison's disease (1.77). CUP risk is known to be reduced in long‐time users of pain‐relieving nonsteroidal anti‐inflammatory drugs (NSAIDs), such as aspirin. For patients with ankylosing spondylitis and with some other autoimmune diseases, with assumed chronic medication by NSAIDSs, CUP risks decreased in long‐term follow‐up. The overall risk of CUP was increased among patients diagnosed with autoimmune diseases, which call for clinical attention and suggest a possible role of immune dysfunction in CUP. The associations with many autoimmune diseases were weak which may imply that autoimmunity may not synergize with CUP‐related immune dysfunction. However, long‐term NSAID medication probably helped to curtail risks in some autoimmune diseases and CUP risks were generally higher in autoimmune diseases for which NSAIDs are not used and for these CUP appears to be a serious side effect.     

Autoimmune diseases as comorbidities for liver,gallbladder, and biliary duct cancers in Sweden

Background

Autoimmune diseases are associated with many cancers but there is a lack of population-based studies with different autoimmune diseases that have a long follow-up. This is also true of hepatobiliary cancers, which include hepatocellular cancer (HCC) and rarer entities of gallbladder cancer (GBC), intra- and extrahepatic cholangiocarcinoma (iCCA and eCCA), and ampullary cancer.

Methods

Diagnostic data on 43 autoimmune diseases were collected from the Swedish Inpatient Register from 1987 to 2018, and cancer data were derived from the national cancer registry from 1997 onward. Relative risks were expressed as standardized incidence ratios (SIRs).

Results

In a population of 13.6 million, 1.1 million autoimmune diseases were diagnosed and subsequent hepatobiliary cancer was diagnosed in 3191 patients (17.2% of cancers). SIRs for HCC were 2.73 (men) and 2.86 (women), 3.74/1.96 for iCCA, 2.65/1.37 for GBC, 2.38/1.64 for eCCA, and 1.80/1.85 for ampullary cancer. Significant associations between autoimmune disease and HCC were observed for 13 autoimmune diseases, with the highest risks being for autoimmune hepatitis (48.92/73.53, men/women) and primary biliary cirrhosis (38.03/54.48). GBC was increased after six autoimmune diseases, with high SIRs for ulcerative colitis (12.22/3.24) and men with Crohn disease (9.16). These autoimmune diseases were also associated with a high risk of iCCA, which had seven other associations, and eCCA, which had five other associations. Ampullary cancer occurrence was increased after four autoimmune diseases.

Conclusion

An autoimmune disease is a common precursor condition for hepatobiliary cancers. This calls for careful control of autoimmune disease symptoms in each patient and encouragement to practice a healthy lifestyle.     

Autoimmune diseases associated with non-Hodgkin lymphoma: a nationwide cohort study

BackgroundThe cumulative risk of non-Hodgkin lymphoma (NHL) in Sweden by age 80 years has increased to 1.1 in women and 1.6% in men in 2011. Increased risk of NHL associated with personal histories of some autoimmune diseases (ADs) is known. It is unclear whether there are other NHL-related ADs and whether this association holds across different sex, age and year of diagnosis, or NHL histological subtypes.Patients and methodsOver an average of 9.4-year (maximum 47 years) follow-up of 878 161 patients diagnosed in 1964–2010 with 33 different ADs, 3096 subsequent NHL were diagnosed (data: Swedish Cancer Registry).ResultsOf 33 studied ADs, 21 showed significantly increased risk of NHL; 6 of them tended to increase the risk and none significantly decreased it. The overall standardized incidence ratio (SIR) for NHL after ADs was 1.6 [novel findings: immune thrombocytopenic purpura (ITP) = 7.5, polymyositis/dermatomyositis = 4.1, primary biliary cirrhosis = 3.9, myasthenia gravis = 2.2, Behcet = 1.7, rheumatoid fever = 1.7, ulcerative colitis = 1.5, polymyalgia rheumatica = 1.4, and chronic rheumatic heart disease = 1.4; confirmatory findings: autoimmune hemolytic anemia = 27.2, Sjögren = 4.9, Celiac = 4.8, systemic lupus erythematosus = 4.4, polyarteritis nodosa = 2.9, discoid lupus erythematosus = 2.7, sarcoidosis = 2.6, Crohn = 2.1, systemic sclerosis = 2.1, rheumatoid arthritis = 2.0, and Hashimoto/hypothyroidism and psoriasis = 1.4]. SIR for NHL diagnosis before age 60 (2.2) was significantly higher than that in older ages (age ≥60: 1.5). The SIRs in women or men and in period 1993–2010 or 1964–1992 were similar. Risk of all common NHL histology subtypes significantly increased after ADs (cutaneous/peripheral T cell and anaplastic large T and null cell = 2.2; small B-cell lymphocytic = 1.7; diffuse large B cell = 1.6; follicular and mantel cell = 1.3).ConclusionMany of 33 studied ADs (except for ankylosing spondylitis, diabetes type I graves/hyperthyroidism, multiple sclerosis, chorea minor, and pernicious anemia), especially when diagnosed at younger ages, were associated with higher risk of NHL. However, the absolute risk of NHL in many ADs is still small.     

Autoimmune disease and subsequent risk of developing alimentary tract cancers among 4.5 million US male veterans

BACKGROUND:

Autoimmunity is clearly linked with hematologic malignancies, but less is known about autoimmunity and alimentary tract cancer risk, despite the specific targeting of alimentary organs and tissues by several autoimmune diseases. The authors therefore conducted the first systematic evaluation of a broad range of specific autoimmune diseases and risk for subsequent alimentary tract cancer.

METHODS:

On the basis of 4,501,578 US male veterans, the authors identified 96,277 men who developed alimentary tract cancer during up to 26.2 years of follow‐up. By using Poisson regression methods, the authors calculated relative risks (RRs) and 95% confidence intervals.

RESULTS:

A history of autoimmune disease with localized alimentary tract effects generally increased cancer risks in the organ(s) affected by the autoimmune disease, such as primary biliary cirrhosis and liver cancer (RR, 6.01; 95% confidence interval [CI], 4.76‐7.57); pernicious anemia and stomach cancer (RR, 3.17; 95% CI, 2.47‐4.07); and ulcerative colitis and small intestine, colon, and rectal cancers (RR, 2.53; 95% CI, 1.05‐6.11; RR, 2.06; 95% CI, 1.70‐2.48; and RR, 2.07; 95% CI, 1.62‐2.64, respectively). In addition, a history of celiac disease, reactive arthritis (Reiter disease), and systemic sclerosis all were associated significantly with increased risk of esophageal cancer (RR, 1.86‐2.86). Autoimmune diseases without localized alimentary tract effects generally were not associated with alimentary tract cancer risk, with the exception of decreased risk for multiple alimentary tract cancers associated with a history of multiple sclerosis.

CONCLUSIONS:

These findings support the importance of localized inflammation in alimentary tract carcinogenesis. Future research is needed to confirm the findings and improve understanding of underlying mechanisms by which autoimmune diseases contribute to alimentary tract carcinogenesis. Cancer 2011. Published 2010 by the American Cancer Society.     

Personal comorbidities and their subsequent risks for liver,gallbladder and bile duct cancers

Many environmental risk factors for hepatobiliary cancers are known but whether they are associated with specific cancer types is unclear. We present here a novel approach of assessing standardized incidence ratios (SIRs) of previously diagnosed comorbidities for hepatocellular carcinoma (HCC), gallbladder cancer (GBC), cholangiocarcinoma (CCA) and ampullary cancer. The 13 comorbidities included alcohol and nonalcohol related liver disease, chronic obstructive pulmonary disease, gallstone disease, viral and other kinds of hepatitis, infection of bile ducts, hepatic and other autoimmune diseases, obesity and diabetes. Patients were identified from the Swedish Inpatient Register from 1987 to 2018, and their cancers were followed from 1997 onwards. SIRs for HCC were 80 to 100 in men and women diagnosed with hepatitis C virus and they were also >10 in patients diagnosed with hepatitis B virus, other kind of hepatitis, hepatic autoimmune disease and nonalcohol related liver disease. Many of these risks, as well as alcohol related liver disease, were either specific to HCC or were shared with intrahepatic CCA. For GBC, CCA and ampullary cancer infection of bile ducts was the main risk factor. Gallstone disease, nonhepatic autoimmune diseases and diabetes were associated with all hepatobiliary cancers. The limitations of the study include inability to cover some rare risk factors and limited follow-up time. Many of the considered comorbidities are characterized by chronic inflammation and/or overt immune disturbance in autoimmune diseases. The results suggest that local chronic inflammation and a related immune disturbance is the carcinogenic trigger for all these cancers.     

Risk of Cancer Following Hospitalization for Type 2 Diabetes

Objectives.

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

Methods.

T2D patients were obtained from the nationwide Hospital Discharge Register; cancers were recorded from the Swedish Cancer Registry. Standardized incidence ratios (SIRs) were calculated for cancer following last hospitalization for T2D. The comparison group was the general Swedish population.

Results.

The number of hospitalized T2D patients from 1964 to 2007 was 125,126, of whom 26,641 had an affected family member. Altogether 24 cancers showed an elevated risk when follow-up was started after the last hospitalization. The highest SIRs were for pancreatic (6.08) and liver (4.25) cancers. The incidences of these cancers were even elevated when follow-up was started 5 years after the last hospitalization for T2D, with primary liver cancer showing the highest SIR of 4.66. Also increased were the incidences of upper aerodigestive tract, esophageal, colon, rectal, pancreatic, lung, cervical, endometrial, ovarian, and kidney cancers. Prostate cancer showed a lower risk. Familial T2D patients showed no exceptional elevated cancer risks but their prostate cancer and melanoma risks were lower.

Conclusions.

This study, covering approximately one half of Swedish T2D patients, showed an elevated risk for several cancers after hospitalization for T2D, probably indicating the profound metabolic disturbances of the underlying disease. The highest risks were found for liver and pancreatic cancers. No excess cancer risks were observed in familial diabetics. The lower risk for prostate cancer remains intriguing.     

Cancers in the first-degree relatives of children with brain tumours

We used the nationwide Swedish Family-Cancer Database with 2060 childhood brain tumours diagnosed in the period 1958-1996 to analyse the risk of this tumour by parental cancers and in siblings of childhood brain tumour probands. Groups of patients were compared by calculating standardized incidence ratios (SIRs) for brain tumours in offspring. 1.3% of brain tumour patients had a parent with nervous system cancer; SIRs were 2.4 and 1.88 for diagnostic ages < 5 and < 15 years, respectively. The data showed distinct patterns of familial risks for childhood brain tumours, the SIR was 10.26 for brain astrocytoma given a parent with meningioma. Parental colon cancer was associated with offspring ependymoma (SIR 3.70), and parental salivary gland cancers with offspring medulloblastoma (SIR 13.33, but two cases only). SIR for sibling nervous system cancer from childhood brain tumour probands was 3.55 up to age 61.     

Thymoma, thymic hyperplasia, thymectomy and autoimmune diseases (Review)

There is a bidirectional relationship between autoimmunity and cancer: on the one hand, patients with autoimmune conditions develop neoplastic diseases, and on the other hand, malignant conditions are associated with paraneoplastic autoimmune syndromes. Thymoma is an epithelial tumor which is often accompanied by autoimmune diseases: about a third of the patients with thymoma have myasthenia gravis. Pure red cell aplasia, pemphigus and systemic lupus erythematosus, might also coexist with this tumor. Thymectomy is an optional treatment in some autoimmune diseases (i.e. myasthenia gravis, multiple sclerosis, autoimmune hemolytic anemia, ulcerative colitis, and systemic lupus erythematosus). In this communication we review and discuss the coexistence of autoimmune diseases, thymoma or thymic hyperplasia, and the dual effects of thymectomy on their course.     

Risk for incident and fatal prostate cancer in men with a family history of any incident and fatal cancer

BackgroundFamilial clustering of incident prostate cancer and some cancers at other discordant sites has been reported. Less is known about familial clustering of fatal prostate cancer with any fatal discordant cancers. Estimates on familial aggregation based on mortality are free from bias of overdiagnosis.Patients and methodsWe used the nationwide Swedish Family-Cancer Database to calculate standardized incidence ratios (SIRs) for incident prostate cancer for relatives of patients with any common cancer and standardized mortality ratios (SMRs) for death in prostate cancer for relatives of individuals who died from cancer. Similar risks were determined for any common cancer when relatives were affected by prostate cancer.ResultsWe observed familial aggregation of incident and fatal prostate cancers. Familial clustering (SIRs increased) of prostate cancer and of cancers at discordant sites was found for breast, ovarian, and kidney cancers and melanoma. Also, fatal prostate cancer clustered with these and cervical cancers (SMRs increased).ConclusionsOur findings demonstrate that familial aggregation of prostate and breast cancers are not due to shared screening habits. The data on the association of cancers at discordant sites might be useful for clinical counseling and for mechanistic studies searching explanations to the familial clustering between discordant cancers.     

The Swedish Family-Cancer Database: Update,Application to Colorectal Cancer and Clinical Relevance

The Swedish Family-Cancer Database has been used for almost 10 years in the study of familial risks at all common sites. In the present paper we describe some main features of version VI of this Database, assembled in 2004. This update included all Swedes born in 1932 and later (offspring) with their biological parents, a total of 10.5 million individuals. Cancer cases were retrieved from the Swedish Cancer Registry from 1958-2002, including over 1.2 million first and multiple primary cancers and in situ tumours. Compared to previous versions, only 6.0% of deceased offspring with a cancer diagnosis lack any parental information. We show one application of the Database in the study of familial risks in colorectal adenocarcinoma, with defined age-group and anatomic site specific analyses. Familial standardized incidence ratios (SIRs) were determined for offspring when parents or sibling were diagnosed with colon or rectal cancer. As a novel finding it was shown that risks for siblings were higher than those for offspring of affected parents. The excess risk was limited to colon cancer and particularly to right-sided colon cancer. The SIRs for colon cancer in age matched populations were 2.58 when parents were probands and 3.81 when siblings were probands; for right-sided colon cancer the SIRs were 3.66 and 7.53, respectively. Thus the familial excess (SIR-1.00) was more than two fold higher for right-sided colon cancer. Colon and rectal cancers appeared to be distinguished between high-penetrant and recessive conditions that only affect the colon, whereas low-penetrant familial effects are shared by the two sites. Epidemiological studies can be used to generate clinical estimates for familial risk, conditioned on numbers of affected family members and their ages of onset. Useful risk estimates have been developed for familial breast and prostate cancers. Reliable risk estimates for other cancers should also be seriously considered for routine clinical recommendations, because practically all cancers show a familial effect and the risks are high for some of the rare neoplasms. The implementation of a unified management plan for familial cancers at large will be a major challenge to the clinical genetic counselling community.     

The Swedish Family-Cancer Database: Update,Application to Colorectal Cancer and Clinical Relevance

The Swedish Family-Cancer Database has been used for almost 10 years in the study of familial risks at all common sites. In the present paper we describe some main features of version VI of this Database, assembled in 2004. This update included all Swedes born in 1932 and later (offspring) with their biological parents, a total of 10.5 million individuals. Cancer cases were retrieved from the Swedish Cancer Registry from 1958-2002, including over 1.2 million first and multiple primary cancers and in situ tumours. Compared to previous versions, only 6.0% of deceased offspring with a cancer diagnosis lack any parental information. We show one application of the Database in the study of familial risks in colorectal adenocarcinoma, with defined age-group and anatomic site specific analyses. Familial standardized incidence ratios (SIRs) were determined for offspring when parents or sibling were diagnosed with colon or rectal cancer. As a novel finding it was shown that risks for siblings were higher than those for offspring of affected parents. The excess risk was limited to colon cancer and particularly to right-sided colon cancer. The SIRs for colon cancer in age matched populations were 2.58 when parents were probands and 3.81 when siblings were probands; for right-sided colon cancer the SIRs were 3.66 and 7.53, respectively. Thus the familial excess (SIR-1.00) was more than two fold higher for right-sided colon cancer. Colon and rectal cancers appeared to be distinguished between high-penetrant and recessive conditions that only affect the colon, whereas low-penetrant familial effects are shared by the two sites. Epidemiological studies can be used to generate clinical estimates for familial risk, conditioned on numbers of affected family members and their ages of onset. Useful risk estimates have been developed for familial breast and prostate cancers. Reliable risk estimates for other cancers should also be seriously considered for routine clinical recommendations, because practically all cancers show a familial effect and the risks are high for some of the rare neoplasms. The implementation of a unified management plan for familial cancers at large will be a major challenge to the clinical genetic counselling community.     

A malignancy work-up in patients with cancer-associated (paraneoplastic) autoimmune diseases: pemphigus and myasthenic syndromes as cases in point (review)

Although some autoimmune diseases are known to be associated with a higher incidence of cancers, they are not usually considered as paraneoplastic diseases, but rather as autoimmune diseases that may be neoplasia-associated, since currently it is not known whether the tumor leads to their development, or alternatively another underlying condition turns the patients prone to both cancer and autoimmunity. We review the association of cancer with pemphigus, paraneoplastic pemphigus, myasthenia gravis and Eaton-Lambert syndrome, and discuss the importance of looking for an occult malignancy in a patient with a newly-diagnosed autoimmune disease that is known to be associated with cancer.     

Long term mortality after a single treatment course with X-rays in patients treated for ankylosing spondylitis

Mortality up to 1 January 1983 has been studied in 14,106 patients with ankylosing spondylitis given a single course of X-ray treatment during 1935-54. For neoplasms other than leukaemia or colon cancer, mortality was 28% greater than that of members of the general population of England and Wales, and this increase is likely to have been a direct consequence of the treatment. The proportional increase reached a maximum of 71% between 10.0 and 12.4 years after irradiation and then declined. There was only a 7% increase in mortality from these tumours more than 25.0 years after irradiation and only for cancer of the oesophagus was the relative risk significantly raised in this period. Neither the magnitude of the relative risk, nor its temporal pattern following treatment, were greatly influenced by the age of the patient at first treatment. For leukaemia there was a threefold increase in mortality that is also likely to have been due to the radiotherapy. The relative risk was at its highest between 2.5 and 4.9 years after the treatment and then declined, but the increase did not disappear completely, and the risk was still nearly twice that of the general population more than 25.0 years after treatment. There was some evidence that the risks of acute myeloid, acute lymphatic, and chronic myeloid leukaemia were all increased, but no evidence of any increase in chronic lymphatic leukaemia. The relative risk appeared to be greatest for acute myeloid leukaemia. For colon cancer, which is associated with spondylitis through a common association with ulcerative colitis, mortality was increased by 30%. For non-neoplastic conditions there was a 51% increase in mortality that was likely to be associated with the disease itself rather than its treatment. The increase was apparent for a wide range of diseases and was not confined to diseases that have been associated clinically with ankylosing spondylitis.     

Cancer risk in patients with type 2 diabetes mellitus and their relatives

Epidemiological studies indicate that risks of certain cancers are increased in individuals hospitalized for type 2 diabetes mellitus (T2DM), which may not be representative of the entire population of T2DM patients as most of them are treated in primary health cares. To examine the subsequent cancer risk in individuals with T2DM from hospitals and primary health cares, and in their siblings and spouses, standardized incidence ratios (SIRs) were used to assess systematically risks of 35 cancer sites/types in individuals with T2DM using a nationwide Swedish database covering the period 1964 through 2010. Increased SIRs were recorded for 24 cancer sites/types in individuals with T2DM. The highest SIRs were for pancreatic cancer and liver cancer (2.98 and 2.43, respectively). A decreased SIR was noted for prostate cancer. Five cancers showed increased SIRs during the whole follow‐up period: colon, liver, pancreatic, endometrial and kidney cancers. T2DM patients in inpatient, outpatient and primary health care showed similar risk patterns. The overall SIRs for cancer in the siblings and spouses of individuals with T2DM were 0.97 and 1.01, respectively. The insulin users showed an overall increased risk of cancer. This study showed increased risks of 24 cancers in individuals with T2DM, but not in their siblings or spouses, suggesting that the profound metabolic disturbances of the underlying disease may explain the observed increases. Further studies examining the endogenous and exogenous factors underlying these associations are needed.     

Association between tuberculosis infections and non-pulmonary malignancies: a nationwide population-based study

Background:

In addition to lung cancers, tuberculosis infections have been associated with increased risk of non-pulmonary malignancies in case reports. Our population-based study employed standardized incidence ratios (SIRs) to systemically survey non-pulmonary cancer risks after tuberculosis infections.

Methods:

Data of patients who had newly diagnosed tuberculosis, were aged 20 years or older, and had no prior cancer or tuberculosis were sampled from the Taiwan National Health Insurance database between 2000 and 2010. SIRs compared cancer incidence in patients with tuberculosis infections to the general population. SIRs of specific cancers were further analyzed with respect to gender and time after tuberculosis infections.

Results:

After a follow-up period of 28 866 person–years, 530 tuberculosis cases developed cancers compared with 256 cases in the general populations (2.07, 95% confidence interval (CI), 1.90–2.26). The SIR of non-pulmonary malignancies was also increased (1.71, 95% CI, 1.54–1.90). For males, SIRs were increased within 1 year after tuberculosis diagnosis for the following cancers: head and neck, esophageal, colorectal, liver, lung, melanomas, and Hodgkin''s disease. SIRs were increased for liver, biliary, lung, and bladder cancers beyond the first year after tuberculosis diagnosis. For females, SIRs were increased for leukemia, esophageal, and lung cancers within the first year, and only for leukemia beyond 1 year post diagnosis.

Conclusion:

Having found increased risks of several cancers that differ with gender and time after tuberculosis diagnosis, physicians may consider these factors in patients following tuberculosis diagnosis.     

Irritable bowel syndrome and risk of colorectal cancer: a Danish nationwide cohort study

Background:

Little is known about the risk of colorectal cancer among patients with irritable bowel syndrome (IBS).

Methods:

We conducted a nationwide cohort study using data from the Danish National Registry of Patients and the Danish Cancer Registry from 1977 to 2008. We included patients with a first-time hospital contact for IBS and followed them for colorectal cancer. We estimated the expected number of cancers by applying national rates and we computed standardised incidence ratios (SIRs) by comparing the observed number of colorectal cancers with the expected number. We stratified the SIRs according to age, gender, and time of follow-up.

Results:

Among 57 851 IBS patients, we identified 407 cases of colon cancer during a combined follow-up of 506 930 years (SIR, 1.14 (95% confidence interval (CI): 1.03–1.25) and 115 cases of rectal cancer, corresponding to a SIR of 0.67 (95% CI: 0.52–0.85). In the first 3 months after an IBS diagnosis, the SIR was 8.42 (95% CI: 6.48–10.75) for colon cancer and 4.81 (95% CI: 2.85–7.60) for rectal cancer. Thereafter, the SIRs declined and 4–10 years after an IBS diagnosis, the SIRs for both colon and rectal cancer remained below 0.95.

Conclusion:

We found a decreased risk of colorectal cancer in the period 1–10 years after an IBS diagnosis. However, in the first 3 months after an IBS diagnosis, the risk of colon cancer was more than eight-fold increased and the risk of rectal cancer was five-fold increased. These increased risks are likely to be explained by diagnostic confusion because of overlapping symptomatology.     

Familial association of histology specific breast cancers with cancers at other sites

Breast cancer histologies show important differences in their incidence pattern, method of detection and management. Aggregation of breast cancer occurs also in families diagnosed for cancer at sites different from the breast. Therefore, the familial association of histology specific breast cancers with cancers at other sites is of great interest. The nationwide Swedish Family-Cancer Database was used to calculate standardised incidence ratios (SIRs) for breast cancer when parents or sibling were diagnosed with cancer at the most common sites. Significant SIRs were found when parents had breast, ovarian, laryngeal, endometrial, prostate, lung and colon cancers. If women were diagnosed before the age of 50 years, the SIRs were significant when parents were diagnosed with breast, ovarian, and prostate cancers, and leukaemia, and when siblings were diagnosed with squamous cell skin, pancreatic, breast and endometrial cancers. If mothers were diagnosed with breast cancer, histology-specific SIRs were ranked as comedo > tubular > ductal > lobular; SIR for medullary carcinoma was not significant but it was high when mothers presented with ovarian cancer. Other associations were between the upper aerodigestive tract and lobular, colon and comedo, larynx and ductal cancer. Moreover, cervical cancer was associated with comedo and endometrial cancer with the medullary histology. In conclusion, histology-specific breast cancers were associated with specific cancer sites and the strength of the association varied among histologies.     

Subsequent cancers in patients diagnosed with cancer of unknown primary (CUP): etiological insights?

BackgroundPatterns of subsequent malignancies in patients with cancer of unknown primary (CUP) may provide etiological insight into the primary tumor. The objective of the present study is to quantify risks of the subsequent cancers in CUP patients since such studies are lacking.Patients and methodsA population-based cohort of CUP was identified from the Swedish Family-Cancer Database of year 2008. Standardized incidence ratios (SIRs) were calculated for developing the following malignancies in 31 357 CUP patients from 1975 to 2008.ResultsA total of 755 CUP patients developed subsequent cancers, showing a significantly increased overall SIR of 1.69 (95% confidence interval 1.57–1.81). Among the most common 32 malignancies, increased SIRs were noted for 16 sites. Over 10-fold increases were observed for squamous cell carcinoma at four sites, possibly as a result of uncontrolled human papillomavirus infection due to faltering immune surveillance. The highest SIRs were observed among CUP patients diagnosed at a younger age and during the first follow-up year.ConclusionsSwedish CUP survivors had a higher risk of developing many subsequent cancers. Different patterns of risk excess may be suggestive of possible roles for disease- and therapy-related immunosuppression, reappearance of hidden primary tumors, or genetic predisposition.     

A population‐based assessment of mortality and morbidity patterns among patients with thymoma

Thymomas are rare tumors of the mediastinum; a limited number of small studies have evaluated the outcomes in these patients. We identified 668 patients with thymoma from the Swedish Cancer Registry, and 2,719 population‐based matched controls. We obtained information on autoimmunity from the nationwide inpatient/outpatient hospital discharge Registry. We constructed Kaplan‐Meier curves for survival analysis, conditional regression and Cox proportional hazards models to evaluate the association between thymoma and autoimmune diseases, and standardized incidence ratios (SIRs) to evaluate the risk for second cancers following thymoma. Compared with controls, patients with benign or malignant thymoma had a poorer (p < 0.001) 5‐year (79%, 53% vs. 91%), 10‐year (65%, 39% vs. 78%) and 20‐year (43%, 18% vs. 55%) overall survival. For thymoma patients, younger age at diagnosis and being diagnosed in recent years were associated with a better survival. Compared with controls, thymoma patients were more likely to have an autoimmune disease at some point during their lives (32.7% vs. 2.4%, respectively, p < 0.001), most frequently myasthenia gravis (24.5%), systemic lupus erythematosus (2.4%) and red cell aplasia (1.2%). Thymoma patients had twofold excess risk for second cancers compared with the general population, most notably: non‐melanoma skin cancer (SIR = 10.6, 95% confidence intervals (CI) = 6.0–17.3), non‐Hodgkin lymphoma (SIR = 6.8, 95% CI = 3.00–13.0), and cervical (SIR = 6.9, 95% CI = 1.4–20.1), endocrine (SIR = 4.7, 95% CI = 1.3–12.0), and prostate cancer (SIR = 3.0, 95% CI = 1.7–4.8). Despite the improved survival for thymoma patients over time, they have worse survival than controls. Thymoma patients are in need for follow‐up to detect and manage autoimmune diseases and cancer.