Martha J. Felini

DNA Repair Polymorphisms XRCC1 and MGMT and Risk of Adult Gliomas

X-ray cross complementing group 1 (XRCC1) and O6-methylguanine-DNA methyltransferase (MGMT) are pivotal repair genes focused on repairing lesions due to ionizing radiation, alkylating agents, and oxidative DNA damage, risk factors previously linked to gliomas. Using the population based San Francisco Adult Glioma study, we evaluated associations between XRCC1 Arg399Gln, MGMT Leu84Phe, and MGMT Ile143Val polymorphisms with glioma risk among white cases (n = 441 to 453) and controls (n = 487 to 526). We found no evidence of an association between XRCC1 genotypes and glioma. We observed a weak positive association for the MGMT Leu84Phe polymorphism (Leu or Phe/Phe versus Leu/Leu: adjusted OR = 1.26; CI 0.90–1.75) and the MGMT Ile143Val polymorphism (Ile or Val/Val versus Ile/Ile: adjusted OR = 1.20; CI 0.85–1.71).

Occupation and adult gliomas in the San Francisco Bay Area

The etiology of gliomas is not well understood. Some jobs might involve sustained and elevated exposures to carcinogens. This study compares lifetime job histories of 879 glioma cases diagnosed between August 1991 to April 1994 and May 1997 to August 1999 in the San Francisco Bay Area and 864 controls. Logistic analyses compared longest and ever held occupations of 1 year or more for all astrocytic and nonastrocytic cases and controls overall with adjustment for age, gender, and ethnicity and separately for men and women. Two-fold or higher or statistically significant elevated odds ratios were found overall and in men among those with longest held occupations, as firefighters, physicians, material moving equipment operators, and janitors; such elevated odds ratios were also observed for longest-held occupations among male motor vehicle operators and personal service workers and female messengers, legal/social service workers, electronic equipment operators, painters, and food processors. Odds ratios of 0.50 or less, but not statistically significant, were found for those with longest held jobs as writers/journalists, biological scientists, paper workers, mechanics, chemists, and photographers/photoprocessors. This study supports previously observed occupational associations and is one of the few studies with sufficient numbers to separately analyze occupations by gender.

Acute myeloid leukemia incidence following radiation therapy for localized or locally advanced prostate adenocarcinoma

INTRODUCTION The effect of radiation therapy on acute myeloid leukemia incidence among prostate cancer patients has not been sufficiently elucidated despite evidence that acute myeloid leukemia is a consequence of therapeutic radiation in other primary malignancies. Therefore, we investigated the effect of definitive therapy with radiation therapy (external beam radiation therapy [EBRT] or brachytherapy) on acute myeloid leukemia incidence in a population-based cohort of patients with localized or locally advanced prostate cancer. METHODS We utilized the Surveillance, Epidemiology, and End Results database to identify a cohort of men (n=168,612) with newly diagnosed prostate adenocarcinoma between January 1988 and December 2003. Cox proportional hazard regression was used to estimate the hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of acute myeloid leukemia incidence following definitive therapy with EBRT alone, brachytherapy alone, or surgery alone compared to no definitive therapy (i.e. no EBRT, brachytherapy, or surgery). RESULTS The cohort yielded 184 acute myeloid leukemia cases during 1,064,820 person-years of follow-up after prostate adenocarcinoma diagnosis. Patients treated with EBRT had a higher adjusted relative risk of developing acute myeloid leukemia than patients treated with brachytherapy or surgery when each therapy group was compared to patients who were not treated with definitive therapy (EBRT: HR=2.05, 95% CI 1.29, 3.26; brachytherapy: HR=1.22, 95% CI 0.46, 3.22; surgery: HR=1.24, 95% CI 0.77, 1.98). CONCLUSIONS Our findings suggest that acute myeloid leukemia incidence is a greater concern for patients treated with EBRT than brachytherapy for localized or locally advanced prostate adenocarcinoma.

A pilot case-cohort study of liver and pancreatic cancers in poultry workers.

PURPOSE To test the hypothesis that exposure to poultry oncogenic viruses that widely occurs occupationally in poultry workers and in the general population, may be associated with increased risks of deaths from liver and pancreatic cancers, and to identify new risk factors. METHODS A pilot case-cohort study of both cancers within a combined cohort of 30,411 highly exposed poultry workers and 16,408 control subjects was conducted, and risk assessed by logistic regression odds ratios (OR) and proportional hazards risk ratios. RESULTS New occupational findings were recorded respectively for pancreatic/liver cancers, for slaughtering of poultry (OR = 8.9, 95% confidence interval [CI]: 2.7-29.3)/OR = 9.1, 95% CI: 1.9-42.9); catching of live chickens (OR = 3.6, 95% CI: 1.2-10.9)/OR = 1.0, 95% CI: 0.1-8.5); killing other types of animals for food (OR = 4.8, 95% CI: 1.5-16.6)/OR = 2.0, 95% CI: 0.2-18.2), and ever worked on a pig raising farm (OR = 3.0, 95% CI: 1.0-8.2) for pancreatic cancer only. New non-occupational findings for liver cancer were for receiving immunization with yellow fever vaccine (OR = 8.7, 95% CI: 1.0-76.3); and vaccination with typhoid vaccine (OR = 6.3, 95% CI: 1.1-37.4). The study also confirmed previously reported risk factors for both diseases. CONCLUSIONS This study provides preliminary evidence that exposure to poultry oncogenic viruses may possibly be associated with the occurrence of liver and pancreatic cancers. Case-control studies nested within occupational cohorts of highly exposed subjects of sufficient statistical power may provide an efficient and valid method of investigating/confirming these findings.

Update of cancer and non-cancer mortality in the Missouri poultry cohort.

BACKGROUND workers in poultry slaughtering and processing plants have one of the highest human exposures to transmissible agents that cause cancer and other diseases in chickens and turkeys, and also have other occupational carcinogenic exposures. The general population is also exposed to these transmissible agents. METHODS we investigated mortality in workers who belong to a poultry union in Missouri, and estimated standardized mortality ratios. RESULTS significantly increased mortality was observed for some leukemias, benign neoplasms, thyroid diseases, bacterial infections, and schizophrenic disorders. The risk of breast cancer and several non-cancer conditions was significantly depressed. CONCLUSION the findings add to the growing evidence suggesting that workers occupationally exposed to transmissible agents and carcinogens in the poultry industry, are at increased risk of dying from certain chronic diseases, including cancer.

A case–cohort study of lung cancer in poultry and control workers: occupational findings

Objectives We conducted a mortality study of members of the United Food and Commercial Workers International Union who worked in poultry slaughtering/processing plants, and controls. Excess deaths from cancer at 11 different cancer sites including lung cancer were observed in the poultry workers. The study described here is a pilot case–cohort study of lung cancer nested within the cohort to examine if it is possible, in a larger study to be conducted later, to identify specific potentially carcinogenic occupational exposures in poultry workers. Methods Subjects or the next of kin of deceased subjects were interviewed by phone. Logistic regression ORs and Cox proportional HRs were estimated. Results Elevated risks for poultry exposure were recorded for subjects who (1) killed chickens at work (OR 4.2, 95% CI 1.2 to 14.7; HR 1.8, 95% CI 1.0 to 3.3) and (2) ever had direct contact with chicken blood at work (OR 1.9, 95% CI 1.0 to 3.8; HR 1.3, 95% CI 0.9 to 2.0). These activities are associated with high exposure to oncogenic viruses. Conclusion These results may have important public health implications, since the general population is also exposed to these viruses. Elevated risks were observed for non-poultry-related occupational exposures such as working in a stockyard, working in a chemical plant, use of chemicals to kill moulds, and working in plants where plastic products were manufactured. These preliminary findings indicate that full scale epidemiological studies of adequate statistical power are needed to examine the role of occupational exposures in cancer occurrence in poultry workers.

Chiropractic and Medical Use of Health Promotion in the Management of Arthritis: Analysis of the 2006 National Health Interview Survey

OBJECTIVE The importance of integrating healthy behavior counseling into routine health care is universal but may depend on the type of medical care provider as well as the conditions presented by patients. The purpose of this study was to evaluate whether health promotion (HP) recommendations for known risk factors of arthritis differed between general medical doctors and doctors of chiropractic (DCs) in a nationally representative US population with arthritis. METHODS Multiple logistic regression models were used for analyses of data from the Sample Adult Core component of the 2006 National Health Interview Survey (n = 6374 diagnosed with arthritis). Analyses were performed separately for recommendation of weight loss and increase in exercise by health profession subtype (chiropractor and medical doctor). RESULTS Comparing the reported HP efforts between DCs and medical doctors (MDs), while adjusting for the effect of physical therapist and body mass index, we observed no significant differences (weight loss: adjusted odds ratio [95% confidence interval] = 0.76 [0.50-1.18]; increased exercise: adjusted odds ratio [95% confidence interval] = 0.87 [0.59-1.29]). CONCLUSION Health promotion efforts to patients with arthritis do not differ significantly between MDs and DCs, as reported by National Health Interview Survey 2006. This investigation makes it difficult to suggest that DCs or MDs are doing all they can do to manage arthritis through suggested modification of lifestyle in their patients. More research specific to what is and can be recommended to those with arthritis should be conducted particularly because it relates to health-promoting behaviors. Given the recent implementation of required clinical competencies in HP into chiropractic college curriculums, future studies regarding translation of HP messages into public practice should be more informative.

Mortality in workers employed in pig abattoirs and processing plants.

OBJECTIVE workers in slaughterhouses and processing plants that handle pigs, and pork butchers/meatcutters have been little studied for health risks associated with employment, in spite of the fact that they are potentially exposed to oncogenic and non-oncogenic transmissible agents and chemical carcinogens at work. We report here on an update of mortality in 510 workers employed in abattoirs and processing plants that almost exclusively handled pigs and pork products. METHODS standardized mortality ratios (SMRs) were estimated for the cohort as a whole, and in subgroups defined by race and sex, using the corresponding US general population mortality rates for comparison. Study subjects were followed up from January 1950 to December 2006, during which time 45% of them died. RESULTS mortality was significantly increased overall in the cohort. A statistically significant excess of deaths was observed for colon and lung cancers in the entire cohort, SMR=2.7 (95% CI, 1.2-5.1), SMR=1.8 (95% CI, 1.1-2.7), respectively. Significant SMRs in the cohort as a whole were also observed for senile and pre-senile psychotic conditions (SMR=5.1, 95% CI, 1.4-13.1), and pneumonia (SMR=2.6, 95% CI, 1.3-4.8). An observed excess of subarachnoid hemorrhage was seen mainly in whites (SMR=10.1, 95% CI, 1.2-36.3). There was a suggestion of an excess of deaths from ischemic heart disease also, but the elevated SMR was confined to men and was not statistically significant. CONCLUSION this study confirms the excess occurrence of lung and colon cancers, and stroke previously reported in this occupational group. New findings are the excess of risk for senile and pre-senile psychotic conditions and pneumonia, which together with the excess of colon cancer appear specific for pig/pork workers, as they were not evident in much larger studies of workers in abattoirs and processing plants handling cattle and sheep. However, caution should be exercised in interpreting these findings, since some of them could have occurred by chance, resulting from our examination of a large number of causes of death in multiple study subgroups. For the moment, the significance of these findings remains unknown until they are confirmed in larger studies of adequate statistical power. Studies that will take into account possible occupational and non-occupational confounding factors are needed.

The association between renal cell carcinoma and multiple myeloma: insights from population‐based data

Study Type – Prevalence (population based cohort)

Addressing uncertainty regarding the utility of carbohydrate antigen-125 as a prognostic marker in non-Hodgkin lymphoma.

Carbohydrate-antigen 125 (CA-125) is a serum biomarker primarily used in ovarian cancer management, but mounting evidence indicates that elevated CA-125 levels may be relevant in other malignant and non-malignant conditions [1]. This evidence prompted several investigations of CA-125 as a potential prognostic marker in non-Hodgkin lymphoma [1]. However, the utility of CA-125 as a prognostic marker in non-Hodgkin lymphoma remains unclear [1]. Some of the uncertainty regarding the utility of CA-125 may be related to the use of a surrogate for the outcome of interest. Several studies that evaluated the performance of CA-125 as a prognostic marker designated advanced stage at diagnosis as the outcome (i.e. stage at diagnosis was assumed a suitable surrogate for mortality). However, survival may be highly heterogeneous among patients with non-Hodgkin lymphoma despite being categorized with the same stage at diagnosis, because of variations in response to therapy, age, histologic subtype, presence of B-symptoms, and comorbidity (particularly human immunodeficiency virus [HIV] status) [2]. A scenario may arise in which CA-125 is a suitable marker for advanced stage non-Hodgkin lymphoma, but a poor predictor of mortality. Therefore, we performed a systematic review of the literature to determine the concordance of conclusions derived from analyses of CA-125 as an independent marker for advanced stage and mortality within the same study, to determine the prognostic value of CA-125. Furthermore, we re-analyzed published data from one of the eligible studies [3] to illustrate that the analytic measure used to evaluate the prognostic value of CA-125 in non-Hodgkin lymphoma may be misleading. We searched PubMed/Medline to identify studies published in English between January 1989 and September 2009 that evaluated the performance of CA-125 as an independent marker for both advanced stage (determined upon entry into the study) and mortality (determined by prospective follow-up) among adult patients with non-Hodgkin lymphoma. We used multiple combinations of the keywords carbohydrate antigen-125, cancer antigen-125, CA125, CA125, non-Hodgkin lymphoma, and NHL to identify potentially eligible studies. Potentially eligible studies were independently screened by two reviewers to select publications for data extraction and analysis. Reviews, case reports, case series, editorials, and letters to the Editor which essentially functioned as reports of a case or case series were excluded from data extraction and analysis. However, reviews were used for backward citation tracking to search for any potentially eligible studies not previously identified. We extracted information regarding the authors’ conclusions regarding the utility of CA-125 as an independent marker for advanced stage and mortality, year of publication, journal type (hematology/oncology,