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A large body of epidemiologic evidence exists for exploring causal associations between cancer and trichloroethylene (TCE) exposure. The U.S. Environmental Protection Agency 2001 draft TCE health risk assessment concluded that epidemiologic studies, on the whole, support associations between TCE exposure and excess risk of kidney cancer, liver cancer, and lymphomas, and, to a lesser extent, cervical cancer and prostate cancer. As part of a mini-monograph on key issues in the health risk assessment of TCE, this article reviews recently published scientific literature examining cancer and TCE exposure and identifies four issues that are key to interpreting the larger body of epidemiologic evidence: a) relative sensitivity of cancer incidence and mortality data ; b) different classifications of lymphomas, including non-Hodgkin lymphoma ; c) differences in data and methods for assigning TCE exposure status ; and d) different methods employed for causal inferences, including statistical or meta-analysis approaches. The recent epidemiologic studies substantially expand the epidemiologic database, with seven new studies available on kidney cancer and somewhat fewer studies available that examine possible associations at other sites. Overall, recently published studies appear to provide further support for the kidney, liver, and lymphatic systems as targets of TCE toxicity, suggesting, as do previous studies, modestly elevated (typically 1.5-2.0) site-specific relative risks, given exposure conditions in these studies. However, a number of challenging issues need to be considered before drawing causal conclusions about TCE exposure and cancer from these data.
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PMID:Trichloroethylene cancer epidemiology: a consideration of select issues. 1696 7

Cancer mortality data collected by the Guam Cancer Registry for the period 1998 through 2002 were analyzed by cancer site, age, and ethnicity. Ethnicity and site specific age-adjusted cancer mortality rates for Guam were calculated utilizing Guam 2000 census data, the US 2000 standard population and compared to U.S. 2002 age-adjusted cancer mortality rates. Age-adjusted cancer mortality rates for ethnic populations represented on Guam, except those of leukemia and non-Hodgkins lymphoma, were high in relation to other population groups and higher than U.S. averages. Some highlights include: 1. Chamorros had high age-adjusted mortality rates for mouth and pharynx (15.5 vs. 2.7 [corrected] U.S.), nasopharynx (9.1 vs. 0.2 U.S.), lung and bronchus (66.9 vs. 54.9 U.S.), colon-rectum-anus (28.6 vs. 19.7 U.S.), breast (32.0 vs. 28.0 U.S.) and prostate cancer (40.9 vs. 27.9 U.S.); 2. Chamorros (6.4 vs. 2.5 U.S.) and Micronesians (6.3) had high and nearly identical age-adjusted mortality rates for cancer of the mouth and pharynx when nasopharyngeal cancers were excluded; 3. Micronesians had the highest mortality rate for liver cancer over all ethnicities documented (43.5 vs. 4.9 U.S.); 4. Asians had the highest mortality rates for pancreatic (12.5 vs. 10.5 U.S.) and cervical cancer (8.5 vs. 2.6 U.S.); 5. Caucasians had the highest mortality rates for leukemia (19.9 vs. 7.5 U.S.) and Non-Hodgkin's lymphoma (17.6 vs. 7.6 U.S.). Suggestions are made for further research on both explaining and ameliorating cancer mortality disparities among ethnic groups on Guam.
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PMID:Ethnic disparities in cancer mortality among residents of Guam. 1705 33

The comparison of cancers occurring excessively among HIV-infected and transplanted individuals may help to elucidate the relationship between immune surveillance, viral infections, and cancer. A longitudinal study was conducted on 2002 HIV-infected Italian subjects, 6072 HIV-infected French individuals, and 2878 Italian recipients of solid organ transplants. Standardized incidence ratios (SIR) and 95% confidence intervals (CI) were computed to quantify the risk for cancer, compared with the French and Italian general populations. The SIRs for all cancers were 9.8 (95% CI: 9.0-10.6) for HIV-infected individuals versus 2.2 (95% CI: 1.9-2.5) for transplant recipients. In both groups, most of the excess risk was attributable to virus-related cancers, such as Kaposi's sarcoma (KS; SIR = 451 in HIV-positive individuals, 125 in transplant recipients), non-Hodgkin's lymphoma (NHL; SIR = 62.1 and 11.1, respectively), and liver cancer (SIR = 9.4 and 4.1, respectively). Significantly increased SIRs for anal cancer and Hodgkin's lymphoma were found only among HIV-positive individuals. Among women younger than 40 years of age, a more than 10-fold increase in cervical cancer risk was found in both groups. Among HIV-infected individuals treatment with highly active antiretroviral therapies drastically reduced SIRs for KS and NHL only. These results show that HIV-infected individuals and transplant recipients share a similar pattern of cancer risk, largely due to virus-related cancers.
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PMID:Immunosuppression and cancer: A comparison of risks in recipients of organ transplants and in HIV-positive individuals. 1717 24

Highly active antiretroviral therapy (HAART) has dramatically reduced the incidence of acquired immunodeficiency syndrome (AIDS) and increased AIDS survival time, but little is known about its impact on cancer. Data from adults in the San Francisco, California, AIDS surveillance registry were computer matched with the California Cancer Registry. Age-, sex-, and race-adjusted standardized incidence ratios (SIRs) were computed, and proportional hazards models evaluated the effect of HAART use on cancer incidence and cancer survival time. Among 14,210 adults with AIDS diagnosed in 1990-2000, 482 non-AIDS-defining cancers were diagnosed. Compared with rates for the general population, significantly increased cancer incidence rates were observed for anal (SIR = 13.4), Hodgkin's lymphoma (SIR = 11.5), liver (SIR = 3.6), oral cavity and pharynx (SIR = 2.6), respiratory (SIR = 2.6), leukemia (SIR = 2.4), skin melanoma (SIR = 2.4), and prostate (SIR = 1.7) cancers. Risk of liver cancer was lower with HAART use (relative hazard (RH) = 0.32). Risk of anal cancer increased after 1995 (RH = 2.9). Respiratory cancer (RH = 0.40) and Hodgkin's lymphoma (RH = 0.17) showed increased cancer survival time with HAART use, while anal cancer survival may have been slightly decreased (RH = 1.4). The impact of HAART on non-AIDS-defining cancer incidence rates and survival is not uniform, and the mechanism(s) responsible for these differences should be investigated further.
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PMID:The impact of highly active antiretroviral therapy on non-AIDS-defining cancers among adults with AIDS. 1734 4

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.
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PMID:Cancer incidence in AIDS patients in Catalonia, Spain. 1734 85

This study is based on data collected from a total of 1196 patients (725 males and 471 females) with histologically confirmed cancer seen in King Khalid University Hospital over a 5-year period between September 1985 to August 1990. Four hundred forty-five patients were non-Saudi (37.20%). The relative frequency and rank of order are determined for various cancers in Saudi patients and total group and compared with the results of the other published studies on cancer epidemiology in Saudi Arabia. The most common cancers among Saudi males were liver, non-Hodgkin's lymphomas, stomach, lung, central nervous system, prostate, lymphoid, leukemias, myeloid leukemias, urinary bladder and Hodgkin's lymphomas, central nervous cancers among Saudi females were breast, thyroid, non-Hodgkin's lymphomas, central nervous system, stomach, myeloid leukemias, esophagus, lymphoid leukemias, liver and ovary. Rank order and relative frequency for liver cancer in both sexes is the highest among any study previously published on the epidemiology of cancer in Saudi Arabia.
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PMID:Cancer at king khalid university hospital, riyadh. 1758 34

This investigation highlighted the risk of cancer in 8074 HIV-infected people and in 2875 transplant recipients in Italy and France. Observed and expected numbers of cancer were compared through sex- and age-standardised incidence ratios (SIRs) and 95% confidence intervals (CIs). After 15 years of follow-up, the cumulative probability of cancer was 14.7% in transplant recipients and 13.3% in HIV-positives. The SIRs for all cancers were 9.8 in HIV-positives and 2.2 in transplants. Kaposi's sarcoma (SIR=451 in HIV-positives, 125 in transplants) and non-Hodgkin lymphoma (SIR=62 and 11.1, respectively) were the most common cancers. A significantly increased SIR for liver cancer also emerged in both groups. The risk of lung cancer was significantly elevated in heart transplant recipients (SIR=2.8), and of borderline statistical significance in HIV-positive people (95% CI:0.9-2.8). Immune depression entails a two-fold increased overall risk of cancers, mainly related to cancers associated with a viral aetiology.
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PMID:Risk of cancer following immunosuppression in organ transplant recipients and in HIV-positive individuals in southern Europe. 1776 27

Data are limited regarding cancer risk in human immunodeficiency virus (HIV)-infected persons with modest immunosuppression, before the onset of acquired immunodeficiency syndrome (AIDS). For some cancers, risk may be affected by highly active antiretroviral therapy (HAART) widely available since 1996. We linked HIV/AIDS and cancer registries in Colorado, Florida and New Jersey. Standardized incidence ratios (SIRs) compared cancer risk in HIV-infected persons (initially AIDS-free) during the 5-year period after registration with the general population. Poisson regression was used to compare incidence across subgroups, adjusting for demographic factors. Among 57,350 HIV-infected persons registered during 1991-2002 (median CD4 count 491 cells/mm(3)), 871 cancers occurred during follow-up. Risk was elevated for Kaposi sarcoma (KS, SIR 1,300 [n = 173 cases]), non-Hodgkin lymphoma (NHL, 7.3 [n = 203]), cervical cancer (2.9 [n = 28]) and several non-AIDS-defining malignancies, including Hodgkin lymphoma (5.6 [n = 36]) and cancers of the lung (2.6 [n = 109]) and liver (2.7 [n = 14]). KS and NHL incidence declined over time but nonetheless remained elevated in 1996-2002. Incidence increased in 1996-2002 compared to 1991-1995 for Hodgkin lymphoma (relative risk 2.7, 95%CI 1.0-7.1) and liver cancer (relative risk infinite, one-sided 95%CI 1.1-infinity). Non-AIDS-defining cancers comprised 31.4% of cancers in 1991-1995, versus 58.0% in 1996-2002. For KS and NHL, risk was inversely related to CD4 count, but these associations attenuated after 1996. We conclude that KS and NHL incidence declined markedly in recent years, likely reflecting HAART-related improvements in immunity, while incidence of some non-AIDS-defining cancers increased. These trends have led to a shift in the spectrum of cancer among HIV-infected persons.
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PMID:Cancer risk in people infected with human immunodeficiency virus in the United States. 1843 50

A record-linkage study was carried out between the Italian AIDS Registry and 24 Italian cancer registries to compare cancer excess among persons with HIV/AIDS (PWHA) before and after the introduction of highly active antiretroviral therapy (HAART) in 1996. Standardised incidence ratios (SIR) were computed in 21951 AIDS cases aged 16-69 years reported between 1986 and 2005. Of 101 669 person-years available, 45 026 were after 1996. SIR for Kaposi sarcoma (KS) and non-Hodgkin lymphoma greatly decreased in 1997-2004 compared with 1986-1996, but high SIRs for KS persisted in the increasingly large fraction of PWHA who had an interval of <1 year between first HIV-positive test and AIDS diagnosis. A significant excess of liver cancer (SIR=6.4) emerged in 1997-2004, whereas the SIRs for cancer of the cervix (41.5), anus (44.0), lung (4.1), brain (3.2), skin (non-melanoma, 1.8), Hodgkin lymphoma (20.7), myeloma (3.9), and non-AIDS-defining cancers (2.2) were similarly elevated in the two periods. The excess of some potentially preventable cancers in PWHA suggests that HAART use must be accompanied by cancer-prevention strategies, notably antismoking and cervical cancer screening programmes. Improvements in the timely identification of HIV-positive individuals are also a priority in Italy to avoid the adverse consequences of delayed HAART use.
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PMID:Pattern of cancer risk in persons with AIDS in Italy in the HAART era. 1922 94

Over the last 30 years, the increasing use of organ and stem cell transplantation and the AIDS epidemic have led to the realization that some, but not all, human cancers occur more frequently in immunosuppressed individuals. With the notable exception of non-melanoma skin cancer (NMSC), most tumors that show strongly increased incidence rates in both transplant recipients and AIDS patients have been found to have a viral etiology. Among these are Kaposi sarcoma, diffuse large cell B-cell lymphoma, cervical cancer, liver cancer, Merkel cell carcinoma and a subset of Hodgkin's disease. A viral etiology for NMSC, i.e., beta- and gamma-subtypes of human papillomavirus, has been suggested and investigated for many years, but remains controversial. In addition, the moderately increased incidence rates of several other cancers in immunosuppressed individuals (e.g., Vajdic and van Leeuwen, Int J Cancer, in press) could indicate that additional infectious causes for at least some human cancers remain to be discovered. The controversy surrounding the role of cutaneous papillomavirus subtypes in the pathogenesis of NMSC illustrates the difficulties encountered when weighing the epidemiological and molecular biology evidence arguing for an involvement of highly prevalent viruses in certain types of cancer.
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PMID:Cancer and viral infections in immunocompromised individuals. 1958 3


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