Who Are You Going to Call? Primary Care Patients’ Disclosure Decisions Regarding Direct–to–Consumer Genetic Testing

Background: Direct–to–consumer genetic testing (DTCGT) offers risk estimates for a variety of complex diseases and conditions, yet little is known about its impact on actual users, including their decisions about sharing the information gleaned from testing. Ethical considerations include the impact of unsolicited genetic information with variable validity and clinical utility on relatives, and the possible burden to the health care system if revealed to physicians. Aims: The qualitative study explored primary care patients’ views, attitudes, and decision making considerations regarding DTCGT. This article focuses on the disclosure decisions participants made regarding participation, testing, and results of DTCGT, a topic which arose as a secondary aim of the study. Methods: Through four longitudinal interviews (pre–test, results, 3 and 12 months post–test) we examined twenty primary care patients’ decisions, expressed intentions, and actions regarding disclosure to immediate and extended family, friends and coworkers, and physicians about participation in and results of DTCGT. Individual interviews were analyzed using qualitative content analysis and a summative approach to describe the global themes. Results: Most participants disclosed to some immediate family; less than half disclosed to extended family; approximately half talked to friends. Most participants stated they would or might disclose to physicians about DTCGT and a few did. Conceptual themes that emerged from the data analysis include ambivalence about disclosure, consistency between intention and actual disclosure behavior and decisions, and conditional information sharing. Conclusions: Participants’ intentional and actual disclosure patterns offer insight into how they view DTCGT, weigh results, and the potential impact of DTCGT

Genetic Polymorphisms of Peroxisome Proliferator-Activated Receptors and the Risk of Cardiovascular Morbidity and Mortality in a Community-Based Cohort in Washington County, Maryland

The primary aim of this study was to examine prospectively the associations between 5 peroxisome proliferator-activated receptor (PPAR) single nucleotide polymorphisms (SNPs) and cardiovascular morbidity and mortality in a community-based cohort study in Washington County, Maryland. Data were analyzed from 9,364 Caucasian men and women participating in CLUE-II. Genotyping on 5 PPAR polymorphisms was conducted using peripheral DNA samples collected in 1989. The followup period was from 1989 to 2003. The results showed that there were no statistically significant associations between the PPAR SNPs and cardiovascular deaths or events. In contrast, statistically significant age-adjusted associations were observed for PPARG rs4684847 with both baseline body mass and blood pressure, and for PPARG rs709158, PPARG rs1175543, and PPARD rs2016520 with baseline cholesterol levels. Future studies should be conducted to confirm these findings and to explore the associations in populations with greater racial and ethnic diversity

Frequencies of single nucleotide polymorphisms in genes regulating inflammatory responses in a community-based population

BACKGROUND: Allele frequencies reported from public databases or articles are mostly based on small sample sizes. Differences in genotype frequencies by age, race and sex have implications for studies designed to examine genetic susceptibility to disease. In a community-based cohort of 9,960 individuals, we compared the allele frequencies of 49 single nucleotide polymorphisms (SNPs) of genes involved in inflammatory pathways to the frequencies reported on public databases, and examined the genotypes frequencies by age and sex. The genes in which SNPs were analyzed include CCR2, CCR5, COX1, COX2, CRP, CSF1, CSF2, IFNG, IL1A, IL1B, IL2, IL4, IL6, IL8, IL10, IL13, IL18, LTA, MPO, NOS2A, NOS3, PPARD, PPARG, PPARGC1 and TNF. RESULTS: Mean(SD) age was 53.2(15.5); 98% were Caucasians and 62% were women. Only 1 out of 33 SNPs differed from the SNP500Cancer database in allele frequency by >10% in Caucasians (n = 9,831), whereas 12 SNPs differed by >10% (up to 50%) in African Americans (n = 105). Two out of 15 SNPs differed from the dbSNP database in allele frequencies by >10% in Caucasians, and 5 out of 15 SNPs differed by >10% in African Americans. Age was similar across most genotype groups. Genotype frequencies did not differ by sex except for TNF(rs1799724), IL2(rs2069762), IL10(rs1800890), PPARG(rs1801282), and CRP(rs1800947) with differences of less than 4%. CONCLUSION: When estimating the size of samples needed for a study, particularly if a reference sample is used, one should take into consideration the size and ethnicity of the reference sample. Larger sample size is needed for public databases that report allele frequencies in non-Caucasian populations

Polymorphisms in estrogen-metabolizing and estrogen receptor genes and the risk of developing breast cancer among a cohort of women with benign breast disease

BACKGROUND: A cohort study was conducted to examine the role of genetic polymorphisms in three estrogen metabolizing enzymes (COMT, CYP1A1, CYP1B1) and the two estrogen receptors (ESR1, ESR2) in the progression of benign breast disease (BBD) to breast cancer. METHODS: Among participants in an ongoing cohort study, 1438 Caucasian women had a breast biopsy for BBD and were successfully genotyped for at least one of the polymorphisms examined in this study. Genotypes were determined using DNA extracted from blood specimens collected in 1989. Incident cases of breast cancer occurring subsequent to BBD diagnosis up to 2003 were identified through cancer registries. RESULTS: Among all participants, the ESR2 *5772G allele was associated with a significant decrease in the risk of breast cancer among women with BBD (Odds Ratio (OR) 0.38; 95% Confidence Interval (CI) 0.15, 0.96). Compared to the reference wild-type genotypes, marginally significant associations with the development of breast cancer were observed between carriers of the variant ESR1 – 104062T allele (OR 0.70, 95% CI 0.45, 1.09), the variant ESR2 *38A allele (OR 1.40; 95% CI 0.88, 2.25), and the variant CYP1B1 453Ser allele (OR 1.48, 95% CI 0.95, 2.32). CONCLUSION: The results indicate that specific polymorphisms in the CYP1B1, ESR1, and ESR2 genes may play a role in progression of BBD to breast cancer among Caucasian women. Although additional studies are needed to confirm or refute our findings, these results suggest that genetic markers may aid in the identification of women who are at risk for progression of BBD to cancer

Historical Comparison of Perfluorooctanesulfonate, Perfluorooctanoate, and Other Fluorochemicals in Human Blood

The purpose of this investigation was to determine whether there has been a change in the human blood concentration of perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA), and five other fluorochemicals since 1974. Blood samples were collected in 1974 (serum) and 1989 (plasma) from volunteer participants of a large community health study. The study included a total of 356 samples (178 from each time period). These samples were analyzed by high-pressure liquid chromatography/tandem mass spectrometry methods. The median 1974 and 1989 fluorochemical concentrations, respectively, were as follows: PFOS, 29.5 ng/mL vs. 34.7 ng/mL; PFOA, 2.3 ng/mL vs. 5.6 ng/mL; perfluorohexanesulfonate (PFHS), 1.6 ng/mL vs. 2.4 ng/mL; and N-ethyl perfluorooctanesulfonamidoacetate (PFOSAA), less than the lower limit of quantitation (LLOQ; 1.6 ng/mL, vs. 3.4 ng/mL). For N-methyl perfluorooctanesulfonamidoacetate (M570), perfluorooctanesulfonamide, and perfluorooctanesulfonamidoacetate, median serum concentrations in both years were less than the LLOQ values (1.0, 1.0, and 2.5 ng/mL, respectively). Statistical analysis of 58 paired samples indicated that serum concentrations of PFOS, PFOSAA, PFOA, PFHS, and M570 were significantly (p < 0.001) higher in 1989 than in 1974. The data from 1989 were then compared with geometric mean fluorochemical concentrations of serum samples collected in 2001 from 108 American Red Cross adult blood donors from the same region. Except for M570, there were no statistically significant (p < 0.05) geometric mean fluorochemical concentration differences between the 1989 and 2001 samples. In conclusion, based on this study population, PFOS and other serum fluorochemical concentrations have increased between 1974 and 1989. Comparison with other regional data collected in 2001 did not suggest a continued increase in concentrations since 1989

Overall and cancer related mortality among patients with ocular inflammation treated with immunosuppressive drugs: retrospective cohort study

Context Whether immunosuppressive treatment adversely affects survival is unclear

Perceptions, prevalence, and patterns of cannabis use among cancer patients treated at 12 NCI-Designated Cancer Centers

BackgroundThe legal climate for cannabis use has dramatically changed with an increasing number of states passing legislation legalizing access for medical and recreational use. Among cancer patients, cannabis is often used to ameliorate adverse effects of cancer treatment. Data are limited on the extent and type of use among cancer patients during treatment and the perceived benefits and harms. This multicenter survey was conducted to assess the use of cannabis among cancer patients residing in states with varied legal access to cannabis.MethodsA total of 12 NCI-Designated Cancer Centers, across states with varied cannabis-access legal status, conducted surveys with a core questionnaire to assess cannabis use among recently diagnosed cancer patients. Data were collected between September 2021 and August 2023 and pooled across 12 cancer centers. Frequencies and 95% confidence intervals for core survey measures were calculated, and weighted estimates are presented for the 10 sites that drew probability samples.ResultsOverall reported cannabis use since cancer diagnosis among survey respondents was 32.9% (weighted), which varied slightly by state legalization status. The most common perceived benefits of use were for pain, sleep, stress and anxiety, and treatment side effects. Reported perceived risks were less common and included inability to drive, difficulty concentrating, lung damage, addiction, and impact on employment. A majority reported feeling comfortable speaking to health-care providers though, overall, only 21.5% reported having done so. Among those who used cannabis since diagnosis, the most common modes were eating in food, smoking, and pills or tinctures, and the most common reasons were for sleep disturbance, followed by pain and stress and anxiety with 60%-68% reporting improved symptoms with use.ConclusionThis geographically diverse survey demonstrates that patients use cannabis regardless of its legal status. Addressing knowledge gaps concerning benefits and harms of cannabis use during cancer treatment is critical to enhance patient-provider communication