Using Molecular Characterization to Support Investigations of Aquatic Facility-Associated Outbreaks of Cryptosporidiosis - Alabama, Arizona, and Ohio, 2016.

Cryptosporidiosis is a nationally notifiable gastrointestinal illness caused by parasitic protozoa of the genus Cryptosporidium, which can cause profuse, watery diarrhea that can last up to 2-3 weeks in immunocompetent patients and can lead to life-threatening wasting and malabsorption in immunocompromised patients. Fecal-oral transmission of Cryptosporidium oocysts, the parasite's infectious life stage, occurs via ingestion of contaminated recreational water, drinking water, or food, or following contact with infected persons or animals, particularly preweaned bovine calves (1). The typical incubation period is 2-10 days. Since 2004, the annual incidence of nationally notified cryptosporidiosis has risen approximately threefold in the United States (1). Cryptosporidium also has emerged as the leading etiology of nationally notified recreational water-associated outbreaks, particularly those associated with aquatic facilities (i.e., physical places that contain one or more aquatic venues [e.g., pools] and support infrastructure) (2). As of February 24, 2017, a total of 13 (54%) of 24 states reporting provisional data detected at least 32 aquatic facility-associated cryptosporidiosis outbreaks in 2016. In comparison, 20 such outbreaks were voluntarily reported to CDC via the National Outbreak Reporting System for 2011, 16 for 2012, 13 for 2013, and 16 for 2014. This report highlights cryptosporidiosis outbreaks associated with aquatic facilities in three states (Alabama, Arizona, and Ohio) in 2016. This report also illustrates the use of CryptoNet, the first U.S. molecularly based surveillance system for a parasitic disease, to further elucidate Cryptosporidium chains of transmission and cryptosporidiosis epidemiology. CryptoNet data can be used to optimize evidence-based prevention strategies. Not swimming when ill with diarrhea is key to preventing and controlling aquatic facility-associated cryptosporidiosis outbreaks (https://www.cdc.gov/healthywater/swimming/swimmers/steps-healthy-swimming.html).

Concordance of pharmacogenetic polymorphisms in tumor and germ line DNA in adult patients with acute myeloid leukemia.

Archived tumor tissue is a useful resource for retrospective studies addressing relationships between genetic polymorphisms and treatment outcomes. However, genotypes determined in tumor and somatic tissues may differ due to cytogenetic and molecular changes associated with malignant transformation and progression. Discordance between germ line and tumor genotypes may be particularly relevant in leukemia because cytogenetic abnormalities are frequent. We compared genotypes determined in DNA extracted from paired pretreatment bone marrow and buccal samples from 80 adult patients with acute myeloid leukemia (AML). Paired AML and buccal DNA samples were genotyped for polymorphisms (21 single nucleotide polymorphisms and 2 gene deletions) on genes encoding proteins involved in drug metabolism (CYP3A4, CYP2C8, CDA, and GSTP1), oxidative stress mechanisms (CAT, MnSOD, GSTT1, GSTM1, GSTA1, and GPX1), drug transport (MDR1, MRP1, and BCRP), and DNA repair (MGMT, XPD, and XRCC1). Genotypes were determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, except GSTM1 and GSTT1, for which deletion genotypes were determined using multiplex PCR. Concordance of genotypes was tested by kappa statistics. kappa statistics for paired AML and buccal DNA samples ranged between 0.94 and 1.00, indicating excellent agreement. The GSTT1 and GSTM1 genotypes were in perfect concordance for the paired samples. Agreement was also excellent for genes at AML chromosome deletion and translocation breakpoints, including MDR1 at 7q21.1 and MRP1 at 16p13.1. Based on these data, genotypes derived from archived AML bone marrow samples were not likely to differ from those from genomic DNA, and archived bone marrow samples may be useful for the conduct of retrospective pharmacogenetic studies.

Regular analgesic use and risk of multiple myeloma.

Analgesic use has been implicated in the chemoprevention of a number of solid tumors, but to date no previous research has focused on the role of analgesics in the etiology of multiple myeloma (MM). We conducted a hospital-based case-control study of 117 patients with primary, incident MM and 483 age and residence matched controls without benign or malignant neoplasms. All participants received medical services at Roswell Park Cancer Institute in Buffalo, NY, and completed a comprehensive epidemiological questionnaire. Participants who reported analgesic use at least once a week for at least 6 months were classified as regular users; individuals who did not use analgesics regularly served as the reference group throughout the analyses. We used unconditional logistic regression analyses to compute crude and adjusted odds ratios (ORs) with corresponding 95% confidence intervals (CIs). Compared to non-users, regular aspirin users were not at reduced risk of MM (adjusted OR=0.99; 95% CI 0.65-1.49), nor were participants with the highest frequency or duration of aspirin use. A significant risk elevation was found for participants who were regular acetaminophen users (adjusted OR=2.95; 95% CI 1.72-5.08). Further, marked increases in risk of MM were noted with both greater frequency (>7 tablets weekly; adjusted OR=4.36; 95% CI 1.70-11.2) and greater duration (>10 years; adjusted OR=3.26; 95% CI 1.52-7.02) of acetaminophen use. We observed no evidence of a chemoprotective effect of aspirin on MM risk, but observed significant risk elevations with various measures of acetaminophen use. Our results warrant further investigation in population-based case-control and cohort studies and should be interpreted with caution in light of the limited sample size and biases inherent in hospital-based studies.

Intakes of selected food groups and beverages and adult acute myeloid leukemia.

Few studies have explored the association between diet and adult acute myeloid leukemia (AML). In a hospital-based case-control study among 111 cases and 439 controls, AML risk was negatively associated with milk intake among women (OR 0.25, 95% CI 0.08-0.73) and tea (OR 0.50, 95% CI 0.23-1.09), and positively associated among women with beer (OR 2.48, 95% CI 1.05-5.85), wine (OR 2.32, 95% CI 1.05-5.09), and beef (OR 4.78, 95% CI 1.35-16.94). Our findings support a role of diet in adult AML; however, further research is needed to explore gender differences in risk.

Opposing effects of aspirin and acetaminophen use on risk of adult acute leukemia.

Regular use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has been hypothesized to be associated with reduced risk of hematologic cancer, although previous results have been inconsistent. The current study investigated the effects of aspirin or acetaminophen use on adult acute leukemia risk among 169 individuals with leukemia and 676 age and sex matched hospital controls with non-neoplastic conditions who completed a comprehensive epidemiologic questionnaire. Results indicate that regular aspirin use may be associated with a modest decrease in leukemia risk [adjusted odds ratio (aOR), 0.84; 95% confidence interval (CI), 0.59-1.21]. In contrast, ever using acetaminophen was associated with elevated leukemia risk (aOR, 1.53; 95% CI, 1.03-2.26). Results did not differ between men and women. Other studies have demonstrated that acetaminophen is associated with transient decreases in DNA repair, and lymphocytes may be particularly susceptible to DNA damage, suggesting a mechanism for the elevated acute leukemia risk observed among acetaminophen users.

Regular use of aspirin or acetaminophen and risk of non-Hodgkin lymphoma.

Regular use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has been hypothesized to be associated with reduced risk of non-Hodgkin lymphoma (NHL), although previous results have been inconsistent. The current study investigated the effects of regular aspirin or acetaminophen use on non-Hodgkin lymphoma risk among 625 individuals with primary, incident NHL and 2512 age and sex matched hospital controls with non-neoplastic conditions who completed a comprehensive epidemiologic questionnaire. Results indicate that regular aspirin use may be associated with decreased NHL risk among men [adjusted odds ratio (aOR) 0.82, 95% confidence interval (CI), 0.65--1.04], but not among women (aOR 0.93, 95% CI, 0.71--1.23). In contrast, regular acetaminophen use was associated with elevated NHL risk among women (aOR 1.71, 95% CI, 1.18--2.50) but not among men (aOR 0.75, 95% CI, 0.48--1.17). Other studies have demonstrated that acetaminophen is associated with transient decreases in DNA repair, and lymphocytes may be particularly susceptible to DNA damage, suggesting a mechanism for the elevated NHL risk observed.

Epidemiology of male breast cancer.

Breast cancer in men is a rare disease, accounting for approximately 1% of all breast cancer cases. Although the epidemiologic literature regarding female breast cancer is extensive, relatively little is known about the etiology of male breast cancer (MBC). This review is intended to summarize the existing body of evidence on genetic and epidemiologic risk factors for breast cancer in men. Overall, the epidemiology of MBC presents similarities with the epidemiology of female breast cancer. Major genetic factors associated with an increased risk of breast cancer for men include BRCA2 mutations, which are believed to account for the majority of inherited breast cancer in men, Klinefelter syndrome, and a positive family history. Suspected genetic factors include AR gene mutations, CYP17 polymorphism, Cowden syndrome, and CHEK2. Epidemiologic risk factors for MBC include disorders relating to hormonal imbalances, such as obesity, testicular disorders (e.g., cryptorchidism, mumps orchitis, and orchiectomy), and radiation exposure. Suspected epidemiologic risk factors include prostate cancer,prostate cancer treatment, gynecomastia, occupational exposures (e.g., electromagnetic fields, polycyclic aromatic hydrocarbons, and high temperatures), dietary factors (e.g., meat intake and fruit and vegetable consumption), and alcohol intake.