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Background: Chronic levels of inflammation are associated with higher risk of many chronic diseases. Physical activity (PA) lowers the risk of cancer, cardiovascular disease (CVD), diabetes and others. One mechanism for PA-induced protection may be through the immune system. We investigated the association between leisure-time PA and peripheral immune cell populations in a large nationally representative sample of the US general population. Methods: A total of 17,093 participants [mean (SE) age of 41.6 (0.3) years] of the National Health and Nutrition Examination Survey 1999–2018 were included. Self-reported leisure-time PA was converted to metabolic equivalent of task hours per week (MET-hrs/wk). White blood cell (WBC) count, WBC ratios, and platelet count were derived. Multivariable linear regression analyses were used to estimate associations between leisure-time PA level and peripheral immune cell populations. Multivariable logistic regression analyses were used to estimate associations between leisure-time PA and metrics of WBC count and neutrophil-to-lymphocyte ratio (NLR) which may predict mortality. Results: A higher leisure-time PA level was associated with a lower WBC count (> 14.0 vs. < 1.2 MET-hrs/wk adjusted mean (95% confidence interval [CI]): 7.12 (6.86, 7.38) vs. 7.38 (7.12, 7.64) 1000 cells/μL, Ptrend < 0.001) and a lower NLR (> 14.0 vs. < 1.2 MET-hrs/wk adjusted mean (95% CI) 2.04 (1.90, 2.18) vs. 2.13 (1.99, 2.28), Ptrend = 0.007). Leisure-time PA level was not associated with lymphocyte-to-monocyte ratio (LMR; Ptrend = 0.25) or platelet-to-lymphocyte ratio (PLR; Ptrend = 0.69). Compared to the lowest leisure-time PA level (< 1.2 MET-hrs/wk), the highest leisure-time PA level (≥ 14.0 MET-hrs/wk) was associated with a lower probability of a high WBC count (> 8.1 × 109 cells/L; odds ratio [OR] = 0.76, 95% CI = 0.66–0.88) and high NLR (> 2.68; OR = 0.84, 95% CI = 0.72–0.99), which may predict CVD and all-cause mortality. The highest leisure-time PA level also linked to a lower probability of a high WBC count (≥ 8.3 × 109 cells/L; OR = 0.76, 95% CI = 0.66–0.88), which may predict cancer mortality. Conclusions: We observed an inverse association between leisure-time PA level, WBC count, and NLR, particularly for neutrophil levels. These results suggest that participants at higher levels of leisure-time PA may have lower levels of inflammation, which may be important for future chronic disease outcomes. Key Points: In this cross-sectional analysis of 17,093 participants, a higher leisure-time physical activity level was associated with a lower white blood cell (WBC) count and a lower neutrophil-to-lymphocyte ratio (NLR). In gender-specific analysis, the inverse association between leisure-time physical activity level and WBC count was consistent in both genders, while the inverse relationship with NLR was observed in women exclusively. Participants at higher levels of leisure-time physical activity may have lower levels of inflammation, which may be important for future chronic disease outcomes. [ABSTRACT FROM AUTHOR]

Demographic characteristics, risk factors, and clinical variables associated with gonorrhea and chlamydial infection in women being treated in emergency departments (EDs) in the United States are incompletely characterized. We used univariable and multivariable regression analyses on 17,411 encounters from women 18 years and older who presented to EDs in northeast Ohio and were tested for gonorrhea or chlamydial infection. There were 1,360 women (7.8%) who had Chlamydia trachomatis infection and 510 (2.9%) who had Neisseria gonorrhoeae infection. Those infected with C. trachomatis or N. gonorrhoeae were younger (23.8 vs. 29.2 years), unmarried (97.7% vs. 90.1%), Black (93.3% vs. 88.0%), infected with Trichomonas vaginalis (39.9% vs. 27.2%), diagnosed with urinary tract infection (15.7% vs. 10.6%), and treated for gonorrhea and chlamydial infection during the ED visit (31.6% vs. 17.4%) (all ps < .001). Women infected with C. trachomatis or N. gonorrhoeae had more urine white blood cells (WBCs) (23.9 vs. 16.4 cells per high-power field [HPF]) and leukocyte esterase (1.2+ vs. 0.8+) on urinalysis. They had more WBCs (18.5 vs. 12.4 cells/HPF) and odds of having T. vaginalis infection (12.8% vs. 8.2%) on vaginal wet preparation (all ps < .001). Women infected with C. trachomatis were more likely to be younger and not Black; they were less likely to be treated for gonorrhea and chlamydial infection in the ED and to have lower levels of urine WBCs, leukocyte esterase, and blood than those infected with N gonorrhoeae (all ps ≤ .05)., Competing Interests: Disclosure: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Melanoma of unknown primary (MUP) is incompletely described on a population level., Objective: We sought to characterize stage IV MUP in a population-based cancer registry., Methods: We developed a novel search algorithm to identify cases of stage IV MUP in the Surveillance, Epidemiology, and End Results 18 registries from 1973 to 2014. Cases of stage IV melanoma of known primary (MKP) served as a comparison group. Age-standardized incidence rates, demographic characteristics, adjusted disease-specific survival, and Cox proportional hazard models were calculated for MUP and MKP., Results: A total of 322 stage IV MUP cases and 12,796 stage IV MKP cases were identified in Surveillance, Epidemiology, and End Results 18 registries from 1973 to 2014. The incidence of stage IV MUP is increasing, particularly for patients younger than 30 years of age. In multivariate analyses, age older than 50 and a lack of surgical treatment were negative prognostic factors for stage IV MUP. Relative survival, but not 5-year adjusted disease-specific survival, was higher for stage IV MUP than for MKP., Limitations: Limitations include the retrospective study design and possible misclassification of MUP., Conclusions: The incidence of stage IV MUP is increasing, and stage IV MUP shares similar prognostic factors with stage IV MKP, including age and surgical treatment., (Copyright © 2018 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Identifying novel melanoma genetic risk factors informs screening and prevention efforts. Mutations in the phenylalanine hydroxylase gene (the causative gene in phenylketonuria) lead to reduced pigmentation in untreated phenylketonuria patients, and reduced pigmentation is associated with greater melanoma risk. Therefore, we sought to characterize the relationship between phenylketonuria carrier status and melanoma risk. Using National Newborn Screening Reports, we determined the United States phenylketonuria/hyperphenylalanemia carrier frequency in Caucasians to be 1.76%. We examined three publically available melanoma datasets for germline mutations in the phenylalanine hydroxylase gene associated with classic phenylketonuria and/or hyperphenylalanemia. Mutations were identified in 29/814 melanoma patients, with a carrier frequency of 3.56%. There was a twofold enrichment (p-value = 3.4 × 10 -5 ) compared to the Caucasian frequency of hyperphenylalanemia/phenylketonuria carriers. These data demonstrate a novel association between phenylalanine hydroxylase carrier status and melanoma risk. Further, functional investigation is warranted to determine the link between phenylalanine hydroxylase mutations and melanomagenesis., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Primary melanoma arising in the genitourinary tract is rare and poorly characterized., Objectives: We sought to describe the epidemiology of genitourinary melanoma in the United States., Methods: Incident case and population data were obtained for genitourinary melanoma from the Surveillance, Epidemiology, and End Results 13 Registries Database between 1992 and 2012., Results: A total of 817 patients with genitourinary melanoma were identified; most cases occurred in the vulva. The incidence of genitourinary melanoma was much higher in women (1.74/1 million person-years) than men (0.17/1 million person-years). The highest rates occurred among non-Hispanic white women aged 85 years and older. Five-year melanoma-specific and overall survival were poor at 52.4% and 36.3%, respectively. Predictors of poor survival were increasing age, black race, and female sex., Limitations: The study population is small, therefore some rates reported may be unstable. In addition, cutaneous, mucosal, and other extracutaneous surfaces of the genitourinary tract cannot be reliably distinguished in Surveillance, Epidemiology, and End Results. Furthermore, melanomas may be underreported to cancer registries., Conclusion: From 1992 to 2012, genitourinary melanoma was 10 times more common in women than men. Survival was poor in women compared with men, which is different from cutaneous melanoma where women have a survival advantage., (Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Obesity is an established risk factor for several malignancies. However, the specific measurement of obesity most relevant to colon neoplasia is still debated, and evidence has suggested gender and racial differences in this measurement. In this study, we sought to compare which measurement--BMI, waist circumference (WC), waist-to-hip ratio (WHR) or waist-to-height ratio (WHtR)--is most strongly associated with development of colon adenomas, a precursor of colon cancer, and to investigate differences in this association between racial groups. We confirmed the strong association between WHR, as a measure of central obesity, and development of colon neoplasia. In our overall analysis, patients in the highest WHR quartile showed a substantial increase in risk of colon adenomas compared to patients in the lowest WHR quartile (odds ratio (OR) = 1.82, 95% confidence interval (CI): 1.12-2.71, P(trend) = 0.0017). In stratified analyses, we noted that strongly associated obesity measures in European Americans were WC (OR = 2.38, 95% CI = 1.45-3.92, P(trend) = 0.0004) and BMI (OR = 2.18, 95% CI = 1.37-3.49, P(trend) = 0.0015), whereas in African Americans, WHR was the strongest and the only obesity measure statistically significantly associated with adenoma risk (OR = 2.12, 95% CI = 1.05-4.30, P(trend) = 0.025). Our data highlight the importance of obesity in the development of early colon neoplasia and suggest substantial racial differences in the measures of obesity most strongly associated with risk of colon adenomas.

Obesity is a known risk factor for colon cancer and higher body mass index (BMI) has been associated with colorectal adenomas, which are precursor lesions to most colorectal cancers. Polymorphisms in the fat-mass and obesity-associated (FTO) gene have been associated with BMI and larger effects in older versus younger children have been reported. However, no studies have examined associations between FTO polymorphisms, BMI throughout adulthood and colorectal adenomas. Therefore, we evaluated associations between FTO polymorphisms (rs1421085, rs17817449, rs8050136, rs9939609, rs8044769), adult BMI (at recruitment, 50s, 40s, 30s, 20s age decades) and colorectal adenomas in 759 Caucasians and 469 African-Americans. We found that the highest versus the lowest BMI tertile at recruitment [odds ratio (OR) = 1.82; 95% confidence interval (CI): 1.07-2.16] and in the 30s (OR = 1.50; 95% CI: 1.04-2.15) was associated with higher adenoma risk. Stratification by ethnicity revealed that these associations only remained significant in Caucasians. We found that, in Caucasians, having two versus no copies of the variant allele in rs17817449, rs8050136 and rs9939609, which are all in strong linkage disequilibrium, was associated with higher BMI in the 30s and 40s but none of the polymorphisms were associated with adenomas. In African-Americans, having one or two copies of the variant in rs17817449 (OR = 0.61; 95% CI: 0.39-0.95) and rs8050136 (OR = 0.59; 95% CI: 0.38-0.93) was associated with colorectal adenomas and, having two variant copies in rs17817449 and rs8050136 was associated with higher BMI at recruitment and in the 40s, respectively. Our results are consistent with prior studies and show for the first time that FTO polymorphisms are associated with colorectal adenomas in African-Americans.

Objectives: The incidence of esophageal adenocarcinoma is on the rise in the United States. In this ecological study using the Surveillance, Epidemiology, and End Results (SEER) program (1973-2001) and national food consumption data (1909-1997), we evaluated the correlation between secular trends of dietary macronutrient intakes and esophageal cancer rates., Methods: Linear regressions were performed to assess the correlation between age-adjusted incidence rates of esophageal cancers and nutrients., Results: The increase in esophageal adenocarcinoma was found to be strongly correlated with the rise in carbohydrate intake (P < 0.0001). The decline in squamous cell carcinoma rates was negatively correlated with carbohydrate intake in the univariate model (P < 0.0001), but this correlation disappeared when adjusted for other nutrients. Correlations of esophageal adenocarcinoma to percentage of calories from corn syrup, representing refined carbohydrates, were statistically significant in the univariate model (P < 0.0001), but decreased in significance in the multivariate model (P= 0.0118). We also found a significant correlation between obesity and esophageal adenocarcinoma (P < 0.0001) during the same time period., Conclusion: Our ecological evaluation suggests that high carbohydrate intake and obesity can account for at least some of the rise in esophageal adenocarcinoma. Within-population studies are needed to clarify these trends.