Background Testicular germ cell tumor (TGCT) incidence increased steadily in recent decades, but causes remain elusive. Germ cell function may be influenced by cannabinoids, and two prior epidemiologic studies report that use of marijuana may be associated with non-seminomatous TGCT. Here we evaluate the relationship between TGCTs and exposure to marijuana and other recreational drugs using a population-based case-control study. Methods 163 TGCT cases diagnosed in Los Angeles County from December 1986 to April 1991 were enrolled with 292 controls matched on age, race/ethnicity and neighborhood. Participants were asked about drug use by structured in-person interview. Odds ratios and 95% confidence intervals were estimated using conditional logistic regression, adjusted for history of cryptorchidism; education; religiosity; and reported use of marijuana, cocaine and amyl nitrite. Results Compared to never use, ever use of marijuana had two-fold increased risk (OR=1.94, 95%CI: 1.02–3.68) while ever use of cocaine was negatively associated with TGCT (OR=0.54, 95%CI: 0.32–0.91). Stratification on tumor histology revealed a specific association of marijuana use with non-seminoma and mixed histology tumors (OR=2.42, 95%CI: 1.08–5.42). Conclusions We observed a specific association of marijuana use with risk of non-seminoma and mixed tumors. This is the first report of a negative association between cocaine use and TGCT risk. Results warrant mechanistic studies of marijuana’s effect on the endocannabinoid system and TGCT risk, and caution that recreational and therapeutic cannabinoids by young men may confer malignant potential to testicular germ cells.

Purpose of Review Cardiovascular disease (CVD) increasingly afflicts people living with HIV (PLWH) in the contemporary era of antiretroviral therapy (ART). Coronary artery disease (CAD) is the most widely studied cardiovascular problem in PLWH; however, less is known about other clinically relevant subtypes of CVD such as heart failure (HF), cerebrovascular disease, sudden cardiac death, pericardial diseases, and pulmonary hypertension. This paper reviews evidence of other subtypes of CVD as emerging issues in the post-ART era. Recent Findings Recent studies have shown that PLWH have higher risk of HF as well as subclinical impairment of left ventricular (LV) mechanics (systolic and diastolic dysfunction) and myocardial abnormalities (fibrosis and steatosis). The underlying mechanisms, however, are not well-understood. A few studies have also shown higher rates of atrial fibrillation and sudden cardiac death in PLWH. Ischemic stroke is the most common stroke type in the post-ART era, with underlying mechanisms like those identified in CAD: chronic inflammation and associated vasculopathy. Studies of great vessels (carotid artery and aorta) and peripheral arterial disease show heterogeneous results. Small subclinical pericardial effusions are common in PLWH in post-ART era. Pulmonary hypertension continues to be an underdiagnosed and potentially fatal complication of HIV infection. Summary PLWH remain at higher risk for all types of CVD including heart failure, stroke, and arrhythmias in the post-ART era. Chronic inflammation may play an important role in this increased risk. More studies are needed to further elucidate the extent of non-coronary CVD in PLWH and the underlying mechanisms for them.

Purpose of Review Introduction of combination antiretroviral therapy (ART) has increased the life expectancy of patients with HIV infection, allowing them to live longer with this chronic medical condition and consequently experiencing conditions such as cardiovascular diseases (CVDs). Several studies have investigated the increased risk of CVD in people living with HIV (PLWH). However, less is known about the exact mechanisms involved in this increased risk. Also, specific guidelines for management of CVD in PLWH have not been developed yet. In this article, we review the recent literature on the mechanisms involved in pathogenesis of CVD in PLWH, with an emphasis on coronary artery disease (CAD). Recent Findings Although initial studies suspected the increased prevalence of traditional CVD risk factors and side effects of ART to be involved in the increased CVD risk in PLWH, recent studies have uncovered the important role of chronic persistent inflammation in this increased risk. In addition, biomarkers of inflammation have been associated with both CVD events and subclinical CAD in this population. Lastly, recent studies and ongoing clinical trials have been investigating medical interventions that aim to reduce inflammation and cardiovascular events. Summary Different mechanisms of inflammation have been examined in PLWH, including subclinical viremia, microbial translocation, and coinfection with other pathogens such as cytomegalovirus. Although inflammatory biomarkers have been consistently associated with CVD and subclinical CVD outcomes, their prognostic value is unknown. Recent and ongoing trials are exploring the benefits of anti-inflammatory drugs, statins, and antimicrobial translocation drugs on both inflammation and CVD risk among PLWH.

Inherited variation at MC1R is associated with elevated melanoma risk among non-Hispanic whites (NHWs). MC1R genetic testing may unmask previously unrecognized disease risk, especially among individuals with few melanoma phenotypic risk factors. We recruited NHW individuals with limited phenotypic risk factors from two primary care clinics in west-central Florida. Participants (n = 1134) were randomized within MC1R genotype risk group (average/higher) to receive mailed precision prevention (i.e., intervention) or generic prevention materials. Participants reported hours of weekday and weekend sun exposure, frequency of intentional outdoor tanning and sun protection behaviors, number of sunburns, indoor tanning episodes, and skin examinations at baseline, and after 6 and 12 months. Among MC1R higher-risk participants, the intervention increased the likelihood of often or always wearing a shirt with sleeves (OR = 1.49, p = 0.03) and seeking shade or using an umbrella (OR = 1.42, p = 0.046), and it decreased the number of sunburns among their young children (β = −0.13, p = 0.03). Intervention effects were not noted among MC1R average-risk participants. Moderation analyses identified intervention effects within subgroups in average-risk and higher-risk participants. Precision prevention information conveying MC1R testing results can increase the practice of some sun protection behaviors among at-risk individuals with limited melanoma risk phenotypes and may provide a cross-generational tool to counteract increasing incidence of melanoma.

Background Individuals from melanoma-prone families have similar or reduced sun-protective behaviors compared to the general population. Studies on trends in sun-related behaviors have been temporally and geographically limited. Methods Individuals from an international consortium of melanoma-prone families (GenoMEL) were retrospectively asked about sunscreen use, sun exposure (time spent outside), sunburns, and sunbed use at several timepoints over their lifetime. Generalized linear mixed models were used to examine the association between these outcomes and birth cohort defined by decade spans, after adjusting for covariates. Results A total of 2407 participants from 547 families across 17 centers were analyzed. Sunscreen use increased across subsequent birth cohorts, and although the likelihood of sunburns increased until the 1950s birth cohort, it decreased thereafter. Average sun exposure did not change across the birth cohorts, and the likelihood of sunbed use increased in more recent birth cohorts. We generally did not find any differences in sun-related behavior when comparing melanoma cases to non-cases. Melanoma cases had increased sunscreen use, decreased sun exposure, and decreased odds of sunburn and sunbed use after melanoma diagnosis compared to before diagnosis. Conclusions Although sunscreen use has increased and the likelihood of sunburns has decreased in more recent birth cohorts, individuals in melanoma-prone families have not reduced their overall sun exposure and had an increased likelihood of sunbed use in more recent birth cohorts. These observations demonstrate partial improvements in melanoma prevention and suggest that additional intervention strategies may be needed to achieve optimal sun-protective behavior in melanoma-prone families.

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Few studies have examined cognitive responses to mailed precision prevention materials. MC1R is a robust, well-described melanoma susceptibility marker. The purpose was to assess cognitive responses to generic or precision prevention materials incorporating MC1R genetic risk. Non-Hispanic White participants (n = 1134) enrolled in a randomized controlled trial received either precision prevention materials incorporating MC1R genetic risk (higher/average) or generic prevention (standard) materials. Six months after baseline, 808 (71.3%) participants reported on the amount of prevention materials read (5-point scale); believability and clarity of materials; intention to change preventive behaviors (7-point Likert scale); and recall of their MC1R genetic risk. Comparisons were conducted using Kruskal–Wallis and chi-squared tests. Overall, participants read most to all (Mdn = 4, IQR = 2) of the prevention materials, reported high believability (Mdn = 7, IQR = 1) and clarity (Mdn = 7, IQR = 1), and moderate intention to change preventive behaviors (Mdn = 5, IQR = 2). Higher-risk participants reported slightly less clarity (Mdn = 6, IQR = 2) than either average-risk (Mdn = 6, IQR = 1, p = 2.50 × 10−3) or standard participants (Mdn = 7, IQR = 1, p = 2.30 × 10−5); and slightly less believability (Mdn = 6, IQR = 1) than standard participants (Mdn = 7, IQR = 1, p = .005). Higher-risk participants were 2.21 times as likely (95% CI = 1.43–3.43) to misremember or forget their risk compared to average-risk participants; misremembering was observed only among higher-risk participants (14%). Mailed precision prevention information were mostly read, highly believable and clear, and resulted in moderate levels of intention to change sun protection behaviors, bolstering the feasibility of population-level precision prevention. Defensive reactions may explain lower clarity, believability, and higher incorrect risk recall among higher-risk participants.

Purpose: Skin cancer incidence is increasing among Hispanics, who experience worse outcomes than non-Hispanic Whites. Precision prevention incorporating genetic testing for (melanocortin-1 receptor) MC1R, a skin cancer susceptibility marker, may improve prevention behavior. Experimental Design: Hispanic participants (n = 920) from Tampa, FL and Ponce, PR, were block-randomized within MC1R higher- and average-risk groups to precision prevention or generic prevention arms. We collected baseline information on demographics, family history of cancer, phenotypic characteristics, health literacy, health numeracy, and psychosocial measures. Participants reported weekday and weekend sun exposure (in hours), number of sunburns, frequency of five sun protection behaviors, intentional outdoor and indoor tanning, and skin examinations at baseline, 3 months, and 9 months. Participants also reported these outcomes for their eldest child ≤10 years old. Results: Among MC1R higher-risk participants, precision prevention increased sunscreen use (OR = 1.74, P = 0.03) and receipt of a clinical skin exam (OR = 6.51, P = 0.0006); and it decreased weekday sun exposure hours (β = −0.94, P = 0.005) and improved sun protection behaviors (β = 0.93, P = 0.02) in their children. There were no significant intervention effects among MC1R average-risk participants. The intervention did not elevate participant cancer worry. We also identified moderators of the intervention effect among both average- and higher-risk participants. Conclusions: Receipt of MC1R precision prevention materials improved some skin cancer prevention behaviors among higher-risk participants and their children and did not result in reduced prevention activities among average-risk participants. Despite these encouraging findings, levels of sun protection behaviors remained suboptimal among participants, warranting more awareness and prevention campaigns targeted to Hispanics Significance: Our results support a precision public health approach to reducing skin cancers among Hispanics, an underserved population in precision medicine, and may additionally improve preventive behaviors among their children.