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.     

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.     

Autoimmune disease and subsequent digestive tract cancer by histology

BackgroundDysregulation of the immune function in autoimmune diseases could potentially lead to cancer development and there is definite evidence linking some autoimmune mechanisms with cancer. We analyzed systematically the occurrence of histology-specific digestive tract cancers in patients diagnosed with 33 different autoimmune diseases in order to address the question of shared susceptibility.Patients and methodsStandardized incidence ratios (SIRs) were calculated for subsequent digestive tract cancers up to the year 2008 and in patients hospitalized for autoimmune disease after the year 1964.ResultsMyasthenia gravis associated with five different cancers with SIRs ranging from 1.35 to 2.78. Pernicious anemia, Crohn disease, ulcerative colitis, systemic lupus erythematosis and psoriasis were also associated with cancers at multiple sites. Rheumatoid arthritis associated with no cancer and the standardized incidence ratio was decreased for colon adenocarcinoma, also in ankylosing spondylitis patients.ConclusionsIncreased risks of cancer were observed in patients with several autoimmune diseases. Myasthenia gravis and pernicious anemia were associated with many cancers; this is possibly related to immunosuppressant medication in myasthenia gravis. The decreased risks in colon and rectal adenocarcinomas in rheumatoid arthritis and ankylosing spondylitis suggest underlying inflammatory mechanisms as the risks may have been suppressed by the use of anti-inflammatory medication.     

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.     

Clustering of concordant and discordant cancer types in Swedish couples is rare

Background

Spouses are exposed to common environmental cancer risk factors during adulthood. Investigating the aggregation of cancer in couples might provide valuable insights into cancer development.

Methods

The 2008 update of the Swedish Family-Cancer Database includes over 2 million couples with at least one child in common with one single partner. We quantified the contribution of shared adulthood environment by standardised incidence ratios (SIRs) and population attributable fractions (PAFs). Estimated SIRs were used to build an etiological map reflecting the similarity of cancers by adult environmental exposures.

Results

Increased risks of concordant types amongst spouses were found for lung, upper aerodigestive tract and skin cancers (SIRs from 1.24 to 1.97),which are probably related to shared exposure to smoking and UV radiation. PAFs were low with the highest value of 1.46% for uterus cancer in wives of men affected by prostate cancer. Further analysis, based on all non-sex-specific concordant and discordant types, revealed a clustering of lung, stomach, pancreas and bladder cancers sharing smoking as a risk factor. This aggregation was used as a cut-point to identify further “novel” clusters.

Conclusion

Shared lifestyles including smoking and drinking habits as well as human papilloma virus infection (HPV) might be associated with an excess of cancer incidence amongst spouses. We observed significantly an increased risk for smoking-related cancers such as lung, upper aerodigestive tract and oesophageal cancers. The present population-based study confirms that the lifestyle shared by spouses plays a minor role in cancer causation. Only strong environmental risk factors such as smoking seem to influence cancer development in adulthood. The proposed etiological map based on 24 cancer types identifies novel clusters - for example, non-Hodgkin lymphoma and leukaemia, bone cancer and myeloma - that are not completely explained by established risk factors. Some of the identified clusters relied on reproduced associations between cancer risks amongst husband and wives; however, the role of chance cannot be excluded.     

Diabetes mellitus,insulin treatment,diabetes duration,and risk of biliary tract cancer and hepatocellular carcinoma in a European cohort

BackgroundEvidence on associations between self-reported diabetes mellitus, diabetes duration, age at diabetes diagnosis, insulin treatment, and risk of biliary tract cancer (BTC) and hepatocellular carcinoma (HCC), independent of general and abdominal obesity is scarce.Patients and methodsWe conducted a prospective analysis in the EPIC-cohort study among 363 426 participants with self-reported diabetes data. Multivariable adjusted relative risks and 95% confidence intervals were estimated from Cox regression models. In a nested case–control subset, analyses were carried out in HCV/HBV-negative individuals.ResultsDuring 8.5 years of follow-up, 204 BTC cases [including 75 gallbladder cancer (GBC) cases], and 176 HCC cases were identified. Independent of body mass index and waist-to-height ratio diabetes status was associated with higher risk of BTC and HCC [1.77 (1.00–3.13) and 2.17 (1.36–3.47)]. For BTC, the risk seemed to be higher in participants with shorter diabetes duration and those not treated with insulin. Regarding cancer subsites, diabetes was only associated with GBC [2.72 (1.17–6.31)]. The risk for HCC was particularly higher in participants treated with insulin. The results were not appreciably different in HCV/HBV-negative individuals.Conclusion(s)This study supports the hypothesis that diabetes is a risk factor for BTC (particularly GBC) and HCC. Further research is required to establish whether diabetes treatment or duration is associated with 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.     

Oral capecitabine for the treatment of hepatocellular carcinoma, cholangiocarcinoma, and gallbladder carcinoma

BACKGROUND: The goal of the current study was to evaluate the efficacy and toxicity of capecitabine in patients with nonresectable hepatobiliary carcinoma. METHODS: The authors performed a retrospective analysis of all patients with hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), or gallbladder carcinoma (GBC) who were ever treated with oral capecitabine. The medical records of 116 patients with hepatobiliary carcinoma who were treated at The University of Texas M. D. Anderson Cancer Center (Houston, TX) between July 1998 and March 1999 were reviewed. RESULTS: A total of 63 patients were treated with capecitabine (37 with HCC, 18 with CCA, 8 with GBC). Capecitabine 1000 mg/m(2) was administered twice daily for 14 days. Treatment was repeated every 21 days. Each patient received 1-15 treatment cycles. Nine patients (14%)-11% of patients with HCC, 6% of patients with CCA, and 50% of patients with GBC-had either a complete response (CR) or a partial response. A CR was radiologically confirmed in one patient with HCC and in two patients with GBC. The median survival times were 10.1 months (95% confidence interval [CI], 4.5-15.7 months) for patients with HCC, 8.1 months (95% CI, 7.4-8.9 months) for patients with CCA, and 9.9 months (95% CI, 4.4-15.4 months) for patients with GBC. The most common toxicity was hand-foot syndrome (37%). Grade 3 thrombocytopenia occurred in 8% of patients with HCC. No other significant toxicities were observed. For all patients, response to treatment was positively correlated with survival and decline in tumor markers. CONCLUSIONS: Capecitabine was found to be safe for patients with hepatobiliary carcinoma, including those with cirrhosis. The antitumor activity of single-agent capecitabine was most pronounced in patients with GBC, was modest in patients with HCC, and was poor in patients with CCA.     

Increased risk of histologically defined cancer subtypes in human immunodeficiency virus-infected individuals: Clues for possible immunosuppression-related or infectious etiology

BACKGROUND:

Malignancies that occur in excess among human immunodeficiency virus (HIV)‐infected individuals may be caused by immunosuppression or infections. Because histologically defined cancer subtypes have not been systematically evaluated, their risk was assessed among people with acquired immunodeficiency syndrome (AIDS).

METHODS:

Analyses included 569,268 people with AIDS from the HIV/AIDS Cancer Match Study, a linkage of 15 US population‐based HIV/AIDS and cancer registries during 1980 to 2007. Standardized incidence ratios (SIRs) were estimated to compare cancer risk in people with AIDS to the general population overall, and stratified by age, calendar period (a proxy of changing HIV therapies), and time since onset of AIDS (a proxy of immunosuppression).

RESULTS:

Sixteen individual cancer histologies or histology groupings manifested significantly elevated SIRs. Risks were most elevated for adult T cell leukemia/lymphoma (SIR = 11.3), neoplasms of histiocytes and accessory lymphoid cells (SIR = 10.7), giant cell carcinoma (SIR = 7.51), and leukemia not otherwise specified (SIR = 6.69). SIRs ranged from 1.4 to 4.6 for spindle cell carcinoma, bronchioloalveolar adenocarcinoma, adnexal and skin appendage neoplasms, sarcoma not otherwise specified, spindle cell sarcoma, leiomyosarcoma, mesothelioma, germ cell tumors, plasma cell tumors, immunoproliferative diseases, acute lymphocytic leukemia, and myeloid leukemias. For several of these cancer subtypes, significant declines in SIRs were observed across calendar periods (consistent with decreasing risk with improved HIV therapies) or increase in SIRs with time since onset of AIDS (ie, prolonged immunosuppression).

CONCLUSIONS:

The elevated risk of certain cancer subtypes in people with AIDS may point to an etiologic role of immunosuppression or infection. Future studies are needed to further investigate these associations and evaluate candidate infectious agents. Cancer 2012. © 2012 American Cancer Society.     

Increased multimodality treatment options has improved survival for Hepatocellular carcinoma but poor survival for biliary tract cancers remains unchanged

BackgroundPrimary hepatobiliary cancer incidence in the UK is rising and survival rates are low. Surgery is the main curative option for these cancers, but multimodality therapies are expanding. The aim of our original study was to determine trends in survival, over an 8-year period, of patients treated for primary hepatobiliary cancers at our tertiary referral Centre.MethodPatients treated for the most common types of primary hepatobiliary cancers, namely Hepatocellular carcinoma (HCC), Cholangiocarcinoma and Gallbladder cancer between January 2009 and December 2016 were retrospectively analysed from a prospective database linked to UK Hospital Episode Statistics data.ResultsA total of 1536 patients with primary hepatobiliary cancers were assessed and treatment plans formulated at our supra-regional specialist Hepatobiliary MDT. The primary hepatobiliary cancers treated were HCC (n = 836), Cholangiocarcinoma (n = 516), and Gallbladder cancer (n = 184). Survival for all the 3 cancers was significantly better with curative treatment. Overall median survival times were 350, 180, and 150 days respectively for HCC, Cholangiocarcinoma and Gallbladder cancer. Excluding best supportive care patients, the respective survival figures were 900, 600, and 400 days. Survival for HCC patients improved over time and was significantly increased in the final 3 years of the study (p ≤ 0.011 for all). Cholangiocarcinoma and Gallbladder cancer survivals were poor and did not change significantly over time.ConclusionHCC outcome has improved in association with expanded multimodal therapies. Survivals for cholangiocarcinoma and gallbladder cancer remain poor in parallel with limited expansion of multimodal therapies highlighting an unmet therapeutic need for biliary tract cancers.     

Associations between autoimmune conditions and hepatobiliary cancer risk among elderly US adults

Growing evidence suggests that people with autoimmune conditions may be at increased risk of hepatobiliary tumors. In the present study, we evaluated associations between autoimmune conditions and hepatobiliary cancers among adults aged ≥66 in the United States. We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data (1992–2013) to conduct a population-based, case–control study. Cases (n = 32,443) had primary hepatobiliary cancer. Controls (n = 200,000) were randomly selected, cancer-free adults frequency-matched to cases by sex, age and year of selection. Using multivariable logistic regression, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) for associations with 39 autoimmune conditions identified via Medicare claims. We also conducted separate analyses for diagnoses obtained via inpatient versus outpatient claims. Sixteen conditions were associated with at least one hepatobiliary cancer. The strongest risk estimates were for primary biliary cholangitis with hepatocellular carcinoma (OR: 31.33 [95% CI: 23.63–41.56]) and primary sclerosing cholangitis with intrahepatic cholangiocarcinoma (7.53 [5.73–10.57]), extrahepatic cholangiocarcinoma (5.59 [4.03–7.75]), gallbladder cancer (2.06 [1.27–3.33]) and ampulla of Vater cancer (6.29 [4.29–9.22]). Associations with hepatobiliary-related conditions as a group were observed across nearly all cancer sites (ORs ranging from 4.53 [95% CI: 3.30–6.21] for extrahepatic cholangiocarcinoma to 7.18 [5.94–8.67] for hepatocellular carcinoma). Restricting to autoimmune conditions diagnosed via inpatient claims, 6 conditions remained associated with at least one hepatobiliary cancer, and several risk estimates increased. In the outpatient restricted analysis, 12 conditions remained associated. Multiple autoimmune conditions are associated with hepatobiliary cancer risk in the US Medicare population, supporting a shared immuno-inflammatory etiology to these cancers.     

Familial and second lung cancers: a nation-wide epidemiologic study from Sweden

The role of hereditary factors in tumor development has been less well understood for lung cancer than for many other human neoplastic diseases. The nation-wide Swedish Family-Cancer Database was used on 10.2 million individuals and 4524 lung cancers to calculate standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for histological subtypes of lung cancer in 0-66-year-old offspring by cancers in family members. Additionally, SIRs for second lung cancers were analyzed. SIRs in offspring for all lung cancer were increased to 1.87 (95% CI 1.66-2.10), adenocarcinoma to 2.15 (1.77-2.59) and squamous cell carcinoma to 1.86 (1.39-2.44) when a parent presented with lung cancer. The familial risk was not dependent on diagnostic age. Lung cancer associated with parental rectal, cervical, kidney, urinary bladder and endocrine gland cancer. The population attributable fraction of familial lung cancer was 2.97%. Risks for second lung cancers were increased in men and women after smoking and life style related sites, and after skin cancer, non-Hodgkin's lymphoma and Hodgkin's disease.     

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.     

Gallbladder Cancer,Treatment Failure and Relapses: the Peritoneum in Gallbladder Cancer

Purpose

This study aims to review gallbladder cancer (GBC) and present current management strategies, factors influencing prognosis, recurrence and areas of consideration.

Methodology

Literature search in PubMed was made and restricted to articles published from 2002 to 2013 using the following keywords: (GBC?+?peritoneum and GBC?+?surgery?+?metastasis/recurrence); abstract evaluation narrowed results to 53 articles. Twenty-six single-institution reports with 2,097 patients among 36 large-scale retrospective studies were obtained and focused on surgical outcomes.

Results

GBC presents late and recurs early with a poor prognosis. There is no definitive time for curative re-resection following incidental diagnosis. Effective surgical strategies for each disease stage remain unclear. Management guidelines are not universally standardised, most institutions utilise protocols based on individual experiences and limitations. Early-stage GBC is curable with complete resection but invisible metastases at unobvious sites remain problematic. In this study, at least 450 patients relapsed, most had peritoneal metastasis. The peritoneum is a common metastatic site, its microenvironment is intrinsically hypoxic, well vascularized and lined with mesothelium overlaying immune aggregates, which express pro-angiogenic and adhesion molecules that are highly selective for tumour growth and evolution. There are no medical/molecular antagonists to inhibit peritoneal carcinomatosis. Peritonectomies have been successfully undertaken; furthermore, GBC responds to some chemotherapy combinations.

Conclusion

This review focused on GBC surgery. Peritoneal carcinomatosis is common. In carefully selected patients, the incorporation of peritoneal disease in cytoreductive surgery and intraperitoneal chemotherapy will inhibit a vehicle for dissemination, eliminate future relapse sites and improve survival. Areas for consideration include universally standardised protocols, clear management guidelines for each stage, effective re-resection timings with guidance on where or how to identify additional disease.     

Increased cancer risks for relatives of very early-onset breast cancer cases with and without BRCA1 and BRCA2 mutations

Background:

Little is known regarding cancer risks for relatives of women with very early-onset breast cancer.

Methods:

We studied 2208 parents and siblings of 504 unselected population-based Caucasian women with breast cancer diagnosed before age 35 years (103 from USA, 124 from Canada and 277 from Australia), 41 known to carry a mutation (24 in BRCA1, 16 in BRCA2 and one in both genes). Cancer-specific standardised incidence ratios (SIRs) were estimated by comparing the number of affected relatives (50% verified overall) with that expected based on incidences specific for country, sex, age and year of birth.

Results:

For relatives of carriers, the female breast cancer SIRs were 13.13 (95% CI 6.57–26.26) and 12.52 (5.21–30.07) for BRCA1 and BRCA2, respectively. The ovarian cancer SIR was 12.38 (3.1–49.51) for BRCA1 and the prostate cancer SIR was 18.55 (4.64–74.17) for BRCA2. For relatives of non-carriers, the SIRs for female breast, prostate, lung, brain and urinary cancers were 4.03 (2.91–5.93), 5.25 (2.50–11.01), 7.73 (4.74–12.62), 5.19 (2.33–11.54) and 4.35 (1.81–10.46), respectively. For non-carriers, the SIRs remained elevated and were statistically significant for breast and prostate cancer when based on verified cancers.

Conclusion:

First-degree relatives of women with very early-onset breast cancer are at increased risk of cancers not explained by BRCA1 and BRCA2 mutations.     

Breast, ovarian, and endometrial malignancies in systemic lupus erythematosus: a meta-analysis

Background:

An increased lymphoma risk is well documented in systemic lupus (SLE). Less attention has been focused on women''s cancers, even though SLE affects mostly females. Our objective was to estimate the risk of breast, ovarian, and endometrial cancers in SLE, relative to the general population.

Methods:

Data were included from five recent studies of large SLE cohorts. The number of cancers observed was determined for each cancer type. The expected number of malignancies was ascertained from general population data. The parameter of interest was the standardised incidence ratio (SIR), the ratio of observed to expected malignancies.

Results:

The five studies included 47 325 SLE patients (42 171 females) observed for 282 553 patient years. There were 376 breast cancers, 66 endometrial cancers, and 44 ovarian cancers. The total number of cancers observed was less than that expected, with SIRs of 0.76 (95% CI: 0.69, 0.85) for breast cancer, 0.71 (95% CI: 0.55, 0.91) for endometrial cancer, and 0.66 (95% CI: 0.49, 0.90) for ovarian cancer.

Conclusions:

Data strongly support a decreased risk of breast, ovarian, and endometrial cancers in SLE. This may be due to inherent differences in women in SLE (vs the general population) regarding endogenous oestrogen, other medications, and/or genetic make-up.     

Is IL-10 −819C/T Gene Polymorphism Modulating the Risk of Gallbladder Disease in North Indian Population?

Background

Gallbladder carcinoma (GBC) is a highly aggressive neoplasm that arises in the background of gall stones and inflammation. Anti-inflammatory cytokine interleukin-10 (IL-10) gene polymorphisms have been associated with susceptibility to various inflammatory diseases and cancers.

Aim of the study

The aim of the present study was to investigate whether IL-10 ?819C/T polymorphism is associated with GBC susceptibility.

Methods

The study subjects comprised 124 GBC patients, 135 patients with symptomatic gallstone disease, and 200 healthy subjects. Genomic DNA was extracted from blood leukocytes and IL-10 ?819C/T gene polymorphism was analyzed by polymerase chain reaction–restriction fragment length polymorphism.

Results

Frequency distributions of IL-10 ?819C/T genotypes were similar in GBC, gallstone patients, and healthy subjects. However, after stratification on the basis of sex, in male GBC patients, the TT genotype of IL-10 ?819C/T polymorphism showed an approximately sevenfold risk (p value?=?0.038; odds ratio?=?6.58; 95% confidence interval?=?1.11–39.11) in the presence of gall stones when compared with gallstone patients.

Conclusion

These results suggest that interplay of sex hormones and IL-10 ?819C/T polymorphism may lead to the susceptibility of gallstone-mediated gallbladder carcinogenesis.     

Cancer incidence in AIDS patients in Catalonia, Spain

HIV infected people and AIDS patients develop cancer more frequently than the general population. The objective of this study was to evaluate the risk of developing cancer among 15 to 69 year old AIDS patients from two geographic areas: Tarragona and Girona provinces, in north-eastern Spain. We have studied invasive and in situ cancers (for all sites) among 1659 AIDS patients from +/-5 years around the date of their AIDS diagnosis by matching the population-based Cancer Registries with the AIDS Registry covering these populations. The periods used in the linkage were 1981-1998 for Tarragona and 1994-1999 for Girona. Sex and age-standardised incidence ratios (SIRs) of observed-to-expected cancers were calculated by type of cancer as a measure of risk. For selected types of cancers, SIRs were also calculated for HIV exposure category. Compared with the general population, incidence of cancer among AIDS patients (invasive and in situ) increased 22.9 fold in men (n=142) and 21.0 fold in women (n=45). High statistically significant SIRs were found for Kaposi's sarcoma (KS) (male, 486.4; female, 1030.0), non-Hodgkin's lymphoma (NHL) (male, 126.1; female, 192.8) and invasive cervical cancer (41.8). High risks were also found for Hodgkin's lymphoma (31.1), liver cancer (29.4) and lung cancer (9.4) in men, and in situ cervical cancer (24.4) in women. For all non-AIDS defining malignant neoplasms as a group SIRs were 3.4 in men and 2.5 in women. Among men, homo/bisexuality was strongly related to risk of KS and NHL. The rates of cervical cancer, Hodgkin's lymphoma, liver cancer and lung cancer were among the highest ever reported linked to HIV infection. For the cervical cancer this could be attributable to the low incidence of this cancer in the general population and to the high prevalence of intravenous drug users among HIV women and probably due to poor preventive strategies in this population.     

The risk of hepatocellular carcinoma among individuals with acquired immunodeficiency syndrome in the United States

BACKGROUND:

Hepatocellular carcinoma (HCC) is a concern among individuals with human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS).

METHODS:

The authors analyzed population‐based registry linkage data from the US HIV/AIDS Cancer Match Study (1980‐2009) to examine the risk and trends of HCC among individuals with AIDS. Standardized incidence ratios (SIRs) were used to measure HCC risk relative to the general population, and Poisson regression was used to calculate incidence rate ratios (RR) comparing incidence among individuals with AIDS. People with AIDS were categorized according to their HIV risk group into high and low hepatitis C virus (HCV) prevalence groups based on their HIV transmission risk category.

RESULTS:

Among 615,150 individuals with AIDS, HCC risk was elevated almost 4 times compared with the risk in the general population (N = 366; SIR, 3.8; 95% confidence interval, 3.5‐4.3). Although HCC incidence increased steadily across calendar periods (P_trend < .0001; adjusted for sex and age), the excess risk in individuals with AIDS compared with the general population remained somewhat constant (SIRs range, 3.5‐3.9) between the monotherapy/dual therapy era (1990‐1995) and the recent highly active antiretroviral therapy era (2001‐2009). In a multivariate model adjusting for sex, race/ethnicity, and attained calendar period, HCC incidence increased with advancing age (P_trend < .0001) and was associated with HIV risk groups with a known higher prevalence of HCV (adjusted RR, 2.2; 95% confidence interval, 1.8‐2.8).

CONCLUSIONS:

HCC incidence in individuals with AIDS has increased over time despite improved HIV treatment regimens, likely reflecting prolonged survival with chronic liver disease. The high incidence in older adults suggests that this cancer will increase in importance with aging of the HIV‐infected population. Cancer 2012. Published 2012 by the American Cancer Society.     

Familial upper aerodigestive tract cancers: incidence trends,familial clustering and subsequent cancers

Familial risks in upper aerodigestive tract cancer have been assessed mainly through case-control studies based on reported but not medically verified cancers in family members. The nationwide Swedish Family-Cancer Database was used to describe the incidence trends for all subsites of upper aerodigestive tract cancer and to calculate standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for the cancer in 0-66-year-old offspring by cancers in family members. Additionally, SIRs for second primary cancer after upper aerodigestive tract cancers were analysed. SIRs in offspring for all upper aerodigestive tract cancer were not significant when a parent presented with concordant cancer. The population attributable fraction of familial upper aerodigestive tract cancer was 0.43%. Risk for subsequent cancers in men and women after upper aerodigestive tract cancer were increased in smoking, alcohol and other life-style related sites and in skin cancer and non-Hodgkin's lymphoma.