Disclosing genetic risk for Alzheimer’s dementia to individuals with mild cognitive impairment

IntroductionThe safety of predicting conversion from mild cognitive impairment (MCI) to Alzheimer’s disease (AD) dementia using apolipoprotein E (APOE) genotyping is unknown.MethodsWe randomized 114 individuals with MCI to receive estimates of 3‐year risk of conversion to AD dementia informed by APOE genotyping (disclosure arm) or not (non‐disclosure arm) in a non‐inferiority clinical trial. Primary outcomes were anxiety and depression scores. Secondary outcomes included other psychological measures.ResultsUpper confidence limits for randomization arm differences were 2.3 on the State Trait Anxiety Index and 0.5 on the Geriatric Depression Scale, below non‐inferiority margins of 3.3 and 1.0. Moreover, mean scores were lower in the disclosure arm than non‐disclosure arm for test‐related positive impact (difference: ‐1.9, indicating more positive feelings) and AD concern (difference: ‐0.3).DiscussionProviding genetic information to individuals with MCI about imminent risk for AD does not increase risks of anxiety or depression and may provide psychological benefits.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154645/1/trc212002_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154645/2/trc212002.pd

Attitudes about pharmacogenomic testing vary by healthcare specialty

Supplementary data</p

Sugar-sweetened beverage and sugar consumption and colorectal cancer incidence and mortality according to anatomic subsite

Background Recent preclinical research strongly suggests that dietary sugars can enhance colorectal tumorigenesis by direct action, particularly in the proximal colon that unabsorbed fructose reaches. Objectives We aimed to examine long-term consumption of sugar-sweetened beverages (SSBs) and total fructose in relation to incidence and mortality of colorectal cancer (CRC) by anatomic subsite. Methods We followed 121,111 participants from 2 prospective US cohort studies, the Nurses&apos; Health Study (1984-2014) and Health Professionals Follow-Up Study (1986-2014), for incident CRC and related death. Cox proportional hazards regression was used to compute HRs and 95% CIs. Results During follow-up, we documented 2733 incident cases of CRC with a known anatomic location, of whom 901 died from CRC. Positive associations of SSB and total fructose intakes with cancer incidence and mortality were observed in the proximal colon but not in the distal colon or rectum (P-heterogeneity &lt;= 0.03). SSB consumption was associated with a statistically significant increase in the incidence of proximal colon cancer (HR per 1-serving/d increment: 1.18; 95% CI: 1.03, 1.34; P-trend = 0.02) and a more pronounced elevation in the mortality of proximal colon cancer (HR: 1.39; 95% CI: 1.13, 1.72; P-trend = 0.002). Similarly, total fructose intake was associated with increased incidence and mortality of proximal colon cancer (HRs per 25-g/d increment: 1.18; 95% CI: 1.03, 1.35; and 1.42; 95% CI: 1.12, 1.79, respectively). Moreover, SSB and total fructose intakes during the most recent 10 y, rather than those from a more distant period, were associated with increased incidence of proximal colon cancer. Conclusions SSB and total fructose consumption were associated with increased incidence and mortality of proximal colon cancer, particularly during later stages of tumorigenesis.N

Predispositional genome sequencing in healthy adults: design, participant characteristics, and early outcomes of the PeopleSeq Consortium

Abstract Background Increasing numbers of healthy individuals are undergoing predispositional personal genome sequencing. Here we describe the design and early outcomes of the PeopleSeq Consortium, a multi-cohort collaboration of predispositional genome sequencing projects, which is examining the medical, behavioral, and economic outcomes of returning genomic sequencing information to healthy individuals. Methods Apparently healthy adults who participated in four of the sequencing projects in the Consortium were included. Web-based surveys were administered before and after genomic results disclosure, or in some cases only after results disclosure. Surveys inquired about sociodemographic characteristics, motivations and concerns, behavioral and medical responses to sequencing results, and perceived utility. Results Among 1395 eligible individuals, 658 enrolled in the Consortium when contacted and 543 have completed a survey after receiving their genomic results thus far (mean age 53.0 years, 61.4% male, 91.7% white, 95.5% college graduates). Most participants (98.1%) were motivated to undergo sequencing because of curiosity about their genetic make-up. The most commonly reported concerns prior to pursuing sequencing included how well the results would predict future risk (59.2%) and the complexity of genetic variant interpretation (56.8%), while 47.8% of participants were concerned about the privacy of their genetic information. Half of participants reported discussing their genomic results with a healthcare provider during a median of 8.0 months after receiving the results; 13.5% reported making an additional appointment with a healthcare provider specifically because of their results. Few participants (< 10%) reported making changes to their diet, exercise habits, or insurance coverage because of their results. Many participants (39.5%) reported learning something new to improve their health that they did not know before. Reporting regret or harm from the decision to undergo sequencing was rare (< 3.0%). Conclusions Healthy individuals who underwent predispositional sequencing expressed some concern around privacy prior to pursuing sequencing, but were enthusiastic about their experience and not distressed by their results. While reporting value in their health-related results, few participants reported making medical or lifestyle changes

Associations of artificially sweetened beverage intake with disease recurrence and mortality in stage III colon cancer: Results from CALGB 89803 (Alliance).

PurposeObservational studies have demonstrated increased colon cancer recurrence and mortality in states of excess energy balance, as denoted by factors including sedentary lifestyle, diabetes, increased dietary glycemic load, and increased intake of sugar-sweetened beverages. Nonetheless, the relation between artificially sweetened beverages, a popular alternative for sugar-sweetened beverages, and colon cancer recurrence and survival is unknown.MethodsWe analyzed data from 1,018 patients with stage III colon cancer who prospectively reported dietary intake during and after chemotherapy while enrolled in a National Cancer Institute-sponsored trial of adjuvant chemotherapy. Using Cox proportional hazards regressions, we assessed associations of artificially sweetened beverage intake with cancer recurrence and mortality.ResultsPatients consuming one or more 12-ounce servings of artificially sweetened beverages per day experienced an adjusted hazard ratio for cancer recurrence or mortality of 0.54 (95% confidence interval, 0.36 to 0.80) when compared to those who largely abstained (Ptrend = .004). Similarly, increasing artificially sweetened beverage intake was also associated with a significant improvement in both recurrence-free survival (Ptrend = .005) and overall survival (Ptrend = .02). Substitution models demonstrated that replacing a 12-ounce serving of a sugar-sweetened beverage with an isovolumetric serving of an artificially sweetened beverage per day was associated with a 23% lower risk of cancer recurrence and mortality (relative risk, 0.77; 95% confidence interval, 0.63 to 0.95; P = .02).ConclusionHigher artificially sweetened beverage consumption may be associated with significantly reduced cancer recurrence and death in patients with stage III colon cancer. This association may be mediated by substitution for sugar-sweetened alternatives. Further studies are needed to confirm these findings

Associations between artificially sweetened beverage intake and colon cancer recurrence and mortality.

<p>Associations between artificially sweetened beverage intake and colon cancer recurrence and mortality.</p

Results of isovolumetric substitution analysis, calculating change in relative risk of patient outcomes with substitution of 1 serving/day of artificially sweetened beverage for sugar-sweetened beverage.

<p>Change in relative risk is displayed for each outcome as a percentage both graphically and in text, with 95% confidence intervals depicted graphically as error bars. Adjusted for age (continuous variable in years), sex (male or female), depth of invasion through bowel wall (binary variable, pT1-2 or pT3-4), number of positive lymph nodes (binary variable, 1–3 nodes or ≥4 nodes), baseline performance status (binary variable, 0 or 1–2), chemotherapy treatment group (binary variable, 5-fluorouracil and leucovorin or irinotecan, 5-fluorouracil, and leucovorin), consistent aspirin use (yes on both questionnaire 1 and 2), and time-varying total calorie intake (continuous variable, in kilocalories per day), physical activity (continuous variable in metabolic equivalent task hours per week), and body mass index (continuous variable in kilogram per meter-squared). <i>P</i> values are two-sided. Abbreviations: CI, confidence interval.</p

Baseline characteristics by artificially sweetened beverage intake (n = 1,018, median follow-up = 7.3 years).

<p>Baseline characteristics by artificially sweetened beverage intake (n = 1,018, median follow-up = 7.3 years).</p

Derivation of the study cohort.

<p>Abbreviations: ASB, artificially sweetened beverages; CAGLB, Cancer and Leukemia Group B; Q1, questionnaire 1 (midway through adjuvant therapy); Q2, questionnaire 2 (6 months after completion of adjuvant therapy). *Caloric intake exclusion = Less than 600 calories or greater than 4,200 calories per day for men and less than 500 calories or greater than 3,500 calories per day for women. † 6 patients in the final sample are missing physical activity in questionnaire 1 and 3 are missing physical activity in questionnaire 2. 1 patient is missing body mass index in questionnaire 1 and 1 is missing body mass index in questionnaire 2.</p