SLCO1B3 and SLCO2B1 genotypes, androgen deprivation therapy, and prostate cancer outcomes: a prospective cohort study and meta-analysis.

Solute carrier organic anion (SLCO) transporters (OATP transporters) are involved in cellular uptake of drugs and hormones. Germline variants in SLCO1B3 and SLCO2B1 have been implicated in prostate cancer progression and therapy response, including to androgen deprivation and statin medications, but results have appeared heterogeneous. We conducted a cohort study of five single-nucleotide polymorphisms (SNPs) in SLCO1B3 and SLCO2B1 with prior evidence among 3208 men with prostate cancer who participated in the Health Professionals Follow-up Study or the Physicians' Health Study, following participants prospectively after diagnosis over 32 years (median, 14 years) for development of metastases and cancer-specific death (lethal disease, 382 events). Results were suggestive of, but not conclusive for, associations between some SNPs and lethal disease and differences by androgen deprivation and statin use. All candidate SNPs were associated with SLCO mRNA expression in tumor-adjacent prostate tissue. We also conducted a systematic review and harmonized estimates for a dose-response meta-analysis of all available data, including 9 further studies, for a total of 5598 patients and 1473 clinical events. The A allele of the exonic SNP rs12422149 (14% prevalence), which leads to lower cellular testosterone precursor uptake via SLCO2B1, was associated with lower rates of prostate cancer progression (hazard ratio per A allele, 0.80; 95% confidence interval, 0.69-0.93), with little heterogeneity between studies (I2, 0.27). Collectively, the totality of evidence suggests a strong association between inherited genetic variation in SLCO2B1 and prostate cancer prognosis, with potential clinical use in risk stratification related to androgen deprivation therapy.

Healthy dietary patterns and risk of prostate cancer in men at high genetic risk.

Prostate cancer has high heritability. Healthy lifestyle has been associated with lower lethal prostate cancer risk among men at increased genetic susceptibility, but the role of healthy dietary patterns remains unknown. We prospectively followed 10,269 genotyped men in the Health Professionals Follow-up Study (1993-2019). Genetic risk was quantified using an established polygenic risk score (PRS). Five dietary patterns were investigated: healthy eating index, Mediterranean, diabetes risk-reducing, hyperinsulinemic and inflammatory diet. Overall and lethal prostate cancer rates (metastatic disease/prostate cancer-specific death) were analyzed using multivariable Cox proportional hazards models. During 26 years of follow-up, 2133 overall and 253 lethal prostate cancer events were documented. In the highest PRS quartile, higher adherence to a diabetes risk-reducing diet was associated with lower rates of overall (top vs. bottom quintile HR [95% CI], 0.74 [0.58-0.94]) and lethal prostate cancer (0.43 [0.21-0.88]). A low insulinemic diet was associated with similar lower rates (overall, 0.76 [0.60-0.95]; lethal, 0.46 [0.23-0.94]). Other dietary patterns showed weaker, but similar associations. In the highest PRS quartile, men with healthy lifestyles based on body weight, physical activity, and low insulinemic diet had a substantially lower rate (0.26 [0.13-0.49]) of lethal prostate cancer compared with men with unhealthy lifestyles, translating to a lifetime risk of 3.4% (95% CI, 2.3%-5.0%) among those with healthy lifestyles and 9.5% (5.3%-16.7%) among those with unhealthy lifestyles. Our findings indicate that lifestyle modifications lowering insulin resistance and chronic hyperinsulinemia could be relevant in preventing aggressive prostate cancer among men genetically predisposed to prostate cancer.

Healthy lifestyle and prostate cancer risk in the Million Veteran Program.

BACKGROUND: This study aims to assess the impact of healthy lifestyle on prostate cancer (PCa) risk in a diverse population. METHODS: Data for 281,923 men from the Million Veteran Program (MVP), a nationwide, health system-based cohort study, were analyzed. Self-reported information at enrollment included smoking status, exercise, diet, family history of PCa, and race/ethnicity. Body mass index (BMI) was obtained from clinical records. Genetic risk was assessed via a validated polygenic score. Cox proportional hazards models were used to assess associations with PCa outcomes. RESULTS: After accounting for ancestry, family history, and genetic risk, smoking was associated with an increased risk of metastatic PCa (hazard ratio [HR], 1.83; 95% confidence interval [CI], 1.64-2.02; p < 10-16) and fatal PCa (HR, 2.73; 95% CI, 2.36-3.25; p < 10-16). Exercise was associated with a reduced risk of fatal PCa (HR, 0.86; 95% CI, 0.76-0.98; p = .03). Higher BMI was associated with a slightly reduced risk of fatal PCa, and diet score was not independently associated with any end point. Association with exercise was strongest among those who had nonmetastatic PCa at MVP enrollment. Absolute reductions in the risk of fatal PCa via lifestyle factors were greatest among men of African ancestry (1.7% for nonsmokers vs. 6.1% for smokers) or high genetic risk (1.4% for nonsmokers vs. 4.3% for smokers). CONCLUSIONS: Healthy lifestyle is minimally related to the overall risk of developing PCa but is associated with a substantially reduced risk of dying from PCa. In multivariable analyses, both exercise and not smoking remain independently associated with reduced metastatic and fatal PCa.

Impact of Family History and Germline Genetic Risk Single Nucleotide Polymorphisms on Long-Term Outcomes of Favorable-Risk Prostate Cancer.

PURPOSE: Family history and germline genetic risk single nucleotide polymorphisms (SNPs) have been separately shown to stratify lifetime risk of prostate cancer. Here, we evaluate the combined prognostic value of family history of prostate and other related cancers and germline risk SNPs among patients with favorable-risk prostate cancer. MATERIALS AND METHODS: A total of 1367 participants from the prospective Health Professionals Follow-up Study diagnosed with low- or favorable intermediate-risk prostate cancer from 1986 to 2017 underwent genome-wide SNP genotyping. Multivariable Cox regression was used to estimate the association between family history, specific germline risk variants, and a 269 SNP polygenic risk score with prostate cancer‒specific death. RESULTS: Family history of prostate, breast, and/or pancreatic cancer was observed in 489 (36%) participants. With median follow-up from diagnosis of 14.9 years, participants with favorable-risk prostate cancer with a positive family history had a significantly higher risk of prostate cancer‒specific death (HR 1.95, 95% CI 1.15-3.32, P = .014) compared to those without any family history. The rs2735839 (19q13) risk allele was associated with prostate cancer‒specific death (HR 1.81 per risk allele, 95% CI 1.04-3.17, P = .037), whereas the polygenic risk score was not. Combined family history and rs2735839 risk allele were each associated with an additive risk of prostate cancer‒specific death (HR 1.78 per risk factor, 95% CI 1.25-2.53, P = .001). CONCLUSIONS: Family history of prostate, breast, or pancreatic cancer and/or a 19q13 germline risk allele are associated with an elevated risk of prostate cancer‒specific death among favorable-risk patients. These findings have implications for how family history and germline genetic risk SNPs should be factored into clinical decision-making around favorable-risk prostate cancer.

Agent orange exposure and prostate cancer risk in the million veteran program.

BACKGROUND: The US government considers veterans to have been exposed to Agent Orange if they served in Vietnam while the carcinogen was in use, and these veterans are often deemed at high risk of prostate cancer (PCa). Here, we assess whether presumed Agent Orange exposure is independently associated with increased risk of any metastatic or fatal PCa in a diverse Veteran cohort still alive in the modern era (at least 2011), when accounting for race/ethnicity, family history, and genetic risk. PATIENTS AND METHODS: Participants in the Million Veteran Program (MVP; enrollment began in 2011) who were on active duty during the Vietnam War era (August 1964-April 1975) were included (n = 301,470). Agent Orange exposure was determined using the US government definition. Genetic risk was assessed via a validated polygenic hazard score. Associations with age at diagnosis of any PCa, metastatic PCa, and death from PCa were assessed via Cox proportional hazards models. RESULTS AND INTERPRETATION: On univariable analysis, exposure to Agent Orange was not associated with increased PCa (hazard ratio [HR]: 1.02, 95% confidence interval [CI]: 1.00-1.04, p = 0.06), metastatic PCa (HR: 0.98, 95% CI: 0.91-1.05, p = 0.55), or fatal PCa (HR: 0.94, 95% CI: 0.79-1.09, p = 0.41). When accounting for race/ethnicity and family history, Agent Orange exposure was independently associated with slightly increased risk of PCa (HR: 1.06, 95% CI: 1.04-1.09, <10-6) but not with metastatic PCa (HR: 1.07, 95% CI: 0.98-1.15, p = 0.10) or PCa death (HR: 1.02, 95% CI: 0.83-1.23, p = 0.09). Similar results were found when accounting for genetic risk. Agent Orange exposure history may not improve modern PCa risk stratification.

An Aggregated Comorbidity Measure Based on History of Filled Drug Prescriptions: Development and Evaluation in Two Separate Cohorts.

BACKGROUND: The ability to account for comorbidity when estimating survival in a population diagnosed with cancer could be improved by using a drug comorbidity index based on filled drug prescriptions. METHODS: We created a drug comorbidity index from age-stratified univariable associations between filled drug prescriptions and time to death in 326,450 control males randomly selected from the general population to men with prostate cancer. We also evaluated the index in 272,214 control females randomly selected from the general population to women with breast cancer. RESULTS: The new drug comorbidity index predicted survival better than the Charlson Comorbidity Index (CCI) and a previously published prescription index during 11 years of follow-up. The concordance (C)-index for the new index was 0.73 in male and 0.76 in the female population, as compared with a C-index of 0.67 in men and 0.69 in women for the CCI. In men of age 75-84 years with CCI = 0, the median survival time was 7.1 years (95% confidence interval [CI] = 7.0, 7.3) in the highest index quartile. Comparing the highest to the lowest drug comorbidity index quartile resulted in a hazard ratio (HR) of 2.2 among men (95% CI = 2.1, 2.3) and 2.4 among women (95% CI = 2.3, 2.6). CONCLUSIONS: A new drug comorbidity index based on filled drug prescriptions improved prediction of survival beyond age and the CCI alone. The index will allow a more accurate baseline estimation of expected survival for comparing treatment outcomes and evaluating treatment guidelines in populations of people with cancer.

Impact of chemotherapy, radiotherapy, and endocrine therapy on sick leave in women with early-stage breast cancer during a 5-year period: a population-based cohort study.

PURPOSE: To examine the influence of type of oncological treatment on sick leave in women of working age with early-stage breast cancer. METHODS: We identified 8870 women aged 30-64 diagnosed with stage I-II breast cancer between 2005 and 2012 in the Breast Cancer Data Base Sweden. Associations between type of oncological treatment (radiotherapy, endocrine therapy, and chemotherapy) and sick leave were estimated by hazard ratios, probabilities, and length of sick leave using multi-state survival analysis. RESULTS: During the first 5 years after diagnosis, women aged 50-54 years at diagnosis receiving chemotherapy spent on average 182 (95% CI 151-218) additional days on sick leave compared with women not receiving chemotherapy, but with otherwise similar characteristics. Correspondingly, women initiating endocrine therapy spent 30 (95% CI 18-44) additional days on sick leave and women receiving post-mastectomy radiotherapy 53 (95% CI 37-69) additional days. At year five, the rate of sick leave was increased in women who had received chemotherapy (HR 1.19, 95% CI 1.11-1.28) or endocrine therapy (HR 1.15, 95% CI 1.05-1.26). Chemotherapy and endocrine therapy were associated with increased rates of sick leave due to depression or anxiety. CONCLUSION: Our findings of increased long-term risks of sick leave after oncological treatment for breast cancer warrant attention from caregivers taking part in cancer rehabilitation. In light of the ongoing debate about overtreatment of early-stage breast cancer, our findings point to the importance of properly selecting patients for chemotherapy not only for the medical toxicity but also the possible impact on their livelihood.

Association of diabetes with stroke and post-stroke dementia: A population-based cohort study.

INTRODUCTION: The impact of prediabetes and diabetes on stroke and the development of dementia after a stroke remain unclear. METHODS: A total of 2655 dementia-free participants (including a stroke-free cohort and a prevalent stroke cohort) were followed-up for 12 years. Dementia and post-stroke dementia were determined by clinical examinations and national registry data. Diabetes was ascertained via medical examination, medication use, medical records, or glycated hemoglobin (HbA1c) ≥6.5%. Prediabetes was defined as HbA1c ≥5.7% in diabetes-free participants. RESULTS: In the stroke-free cohort, 236 participants developed ischemic stroke, and 47 developed post-stroke dementia. Diabetes was associated with ischemic stroke (hazard ratio [HR] 1.76, 95% confidence interval [CI] 1.16 to 2.67) and post-stroke dementia (HR 2.56, 95% CI 1.04 to 6.25). In the prevalent stroke cohort, diabetes was also related to dementia risk. Prediabetes was not significantly related to stroke or post-stroke dementia. DISCUSSION: Diabetes, but not prediabetes, is associated with an increased risk of ischemic stroke and post-stroke dementia.

Loss in working years after a breast cancer diagnosis.

BACKGROUND: Breast cancer can negatively influence working life, but it is unclear how many working years women with breast cancer can expect to lose. METHODS: Women diagnosed with breast cancer between 1997 and 2012 were identified in the Breast Cancer Data Base Sweden (N=19 661), together with breast cancer-free comparison women (N=81 303). Using flexible parametric survival modelling, the loss in working years was calculated as the difference in the remaining years in the work force between women with and without breast cancer. RESULTS: Women aged 50 years at diagnosis with stage I disease lost on average 0.5 years (95% CI, 0.2-0.7) of their remaining working time; the corresponding estimates were 0.9 years (0.5-1.2) in stage II, 2.5 years (1.9-3.1) in stage III and 8.1 years (6.5-9.7) in stage IV. Women with in situ breast cancer did not lose any working years. The strongest treatment determinant was axillary lymph node dissection. CONCLUSIONS: We found a loss in working years not only in late but also in early-stage breast cancer. Although it is reassuring that some groups had no or only a modest work loss, the economic consequences for society are considerable given the large number of women annually diagnosed with breast cancer.

Drug prescription for erectile dysfunction before and after diagnosis of localized prostate cancer.

INTRODUCTION: Despite the high prevalence of erectile dysfunction (ED) in men with prostate cancer, little is known about the use of ED drugs. Also, the possible influence of socioeconomic factors on ED drug use has not been studied previously. AIM: The aim of this study was to examine determinants and patterns of ED drug use before and after diagnosis in men with localized prostate cancer. METHODS: Using a nationwide population-based cohort, 25,390 men with localized prostate cancer diagnosed between 2006 and 2009 and 126,944 control men were identified and followed for filled ED drug prescriptions over a 3-year period, ranging from 1 year before and up to 2 years after diagnosis. MAIN OUTCOME MEASURES: The main outcome measure was the proportion of men with at least one filled ED drug prescription after diagnosis. RESULTS: The number of men using ED drugs increased markedly following diagnosis. Men who underwent radical prostatectomy had the strongest increase, with a cumulative proportion of 74% for at least one filled prescription within the first 2 years after diagnosis. The corresponding proportion was 33% in men treated with radiotherapy, 21% in men on active surveillance, 10% in men on watchful waiting, and 8% in control men. Among men who underwent prostatectomy, usage attenuated over time. Determinants of postdiagnostic use were young age at diagnosis, high income, high education, and a low- or intermediate-risk cancer. CONCLUSION: Although drugs for ED are commonly prescribed after diagnosis, use among most men is transient and influenced by socioeconomic status. Posttreatment counseling and affordable ED drugs are likely to reduce treatment dropout and disparities in use and help improve sexual health and quality of life in men with prostate cancer.

Clinical characteristics, management and survival in young adults diagnosed with malignant melanoma: A population-based cohort study.

BACKGROUND: Few studies to date have described the clinical features of malignant melanoma in young adulthood. Also, little is known about patterns of care in young patients. We examined and compared clinical characteristics, management and survival between young adult (15-39 years) and older adult melanoma patients in Central Sweden. MATERIAL AND METHODS: Patients diagnosed with invasive malignant melanoma between 1997 and 2011 were identified in the Regional Quality Register of Cutaneous Malignant Melanoma in Central Sweden, a population-based register covering a source population of about two million. Data on clinical characteristics, management and survival were retrieved and compared according to age at diagnosis. RESULTS: Of 5915 patients included in the study, 584 (9.9%) were between 15 and 39 years of age at diagnosis. Compared with older patients, young adult patients were more likely to be female, with higher proportions of thin, non-ulcerated melanomas, superficial spreading melanoma and melanomas located on the lower extremity. Young adults had shorter waiting times for surgical procedures and a higher proportion received surgical treatment according to guidelines. Overall, young patients had better relative survival than older patients. Age-related survival differences varied by stage of disease at diagnosis, and were most prominent in stage II disease. CONCLUSION: The observed differences in clinical characteristics, management and survival between young adult and older melanoma patients call for an improved understanding of not only disease etiology but also factors driving management decisions. A better understanding of these differences may help improve care and prognosis for melanoma patients of all ages.

Mortality in women with pregnancy-associated malignant melanoma.

BACKGROUND: Malignant melanoma (MM) is one of the most common malignancies in young women. It remains debated whether a MM diagnosed during pregnancy or lactation has a worse prognosis. OBJECTIVE: We sought to examine mortality in women with pregnancy-associated MM (PAMM) (diagnosed during pregnancy and up to 2-years postpartum). METHODS: This was a population-based cohort study based on information retrieved from the Swedish Cancer and Multi-Generation Registers. Hazard ratios with 95% confidence intervals adjusted for age, period, education, parity, and tumor location were estimated. RESULTS: In total, 6857 women and girls aged 15 to 44 years with a diagnosis of cutaneous MM between 1963 and 2009 were identified. Of these, 1019 cases were classified as PAMM. The cause-specific mortality did not differ between PAMM and MM not diagnosed near childbirth (adjusted hazard ratio 1.09, 95% confidence interval 0.83-1.42). LIMITATIONS: Information on stage at diagnosis was available only for a subset of patients CONCLUSION: Overall, the cause-specific mortality in women and girls with PAMM did not differ from that in women and girls with non-PAMM. The current findings do not provide evidence of an adverse prognostic influence of pregnancy or a recent birth.

Combining magnetic resonance imaging with a multi-ancestry polygenic risk score to improve identification of clinically significant prostate cancer.

Multi-parametric magnetic resonance imaging (mpMRI) has emerged as an important tool for identifying clinically significant prostate cancer. We examined if the addition of a 400-variant multi-ancestry polygenic risk score (PRS) to mpMRI has the potential to improve identification. Based on data from 24 617 men from the Mass General Brigham Biobank, we identified 1243 men who underwent mpMRI. Men in the top PRS quartile were more likely to have clinically significant prostate cancer (47.1% vs 28.6% in the bottom PRS quartile, adjusted relative proportion 1.72 [95% CI = 1.35 to 2.19]). Both among men with a positive and a negative mpMRI, men in the top PRS quartile had the highest frequency of clinically significant cancer. In a constructed scenario for selecting men to undergo biopsy, use of the PRS lowered the frequency of missed clinically significant cancers from 9.1% to 5.9%. Our study provides initial support for using the PRS to improve identification of potentially lethal prostate cancer.

Early Prostate Cancer Deaths Among Men With Higher vs Lower Genetic Risk.

Importance: Prostate cancer, a leading cause of cancer death among men, urgently requires new prevention strategies, which may involve targeting men with an underlying genetic susceptibility. Objective: To explore differences in risk of early prostate cancer death among men with higher vs lower genetic risk to inform prevention efforts. Design, Setting, and Participants: This cohort study used a combined analysis of genotyped men without prostate cancer at inclusion and with lifestyle data in 2 prospective cohort studies in Sweden and the US, the Malmö Diet and Cancer Study (MDCS) and the Health Professionals Follow-Up Study (HPFS), followed up from 1991 to 2019. Data were analyzed between April 2023 and April 2024. Exposures: Men were categorized according to modifiable lifestyle behaviors and genetic risk. A polygenic risk score above the median or a family history of cancer defined men at higher genetic risk (67% of the study population); the remaining men were categorized as being at lower genetic risk. Main Outcomes and Measures: Prostate cancer death analyzed using time-to-event analysis estimating hazard ratios (HR), absolute risks, and preventable deaths by age. Results: Among the 19 607 men included for analysis, the median (IQR) age at inclusion was 59.0 (53.0-64.7) years (MDCS) and 65.1 (58.0-71.8) years (HPFS). During follow-up, 107 early (by age 75 years) and 337 late (after age 75 years) prostate cancer deaths were observed. Compared with men at lower genetic risk, men at higher genetic risk had increased rates of both early (HR, 3.26; 95% CI, 1.82-5.84) and late (HR, 2.26; 95% CI, 1.70-3.01) prostate cancer death, and higher lifetime risks of prostate cancer death (3.1% vs 1.3% [MDCS] and 2.3% vs 0.6% [HPFS]). Men at higher genetic risk accounted for 94 of 107 early prostate cancer deaths (88%), of which 36% (95% CI, 12%-60%) were estimated to be preventable through adherence to behaviors associated with a healthy lifestyle (not smoking, healthy weight, high physical activity, and a healthy diet). Conclusions and Relevance: In this 20-year follow-up study, men with a genetic predisposition accounted for the vast majority of early prostate cancer deaths, of which one-third were estimated to be preventable. This suggests that men at increased genetic risk should be targeted in prostate cancer prevention strategies.

Stockholm3 in a Multiethnic Cohort for Prostate Cancer Detection (SEPTA): A Prospective Multicentered Trial.

PURPOSE: Asian, Black, and Hispanic men are underrepresented in prostate cancer (PCa) clinical trials. Few novel prostate cancer biomarkers have been validated in diverse cohorts. We aimed to determine if Stockholm3 can improve prostate cancer detection in a diverse cohort. METHODS: An observational prospective multicentered (17 sites) clinical trial (2019-2023), supplemented by prospectively recruited participants (2008-2020) in a urology clinic setting included men with suspicion of PCa and underwent prostate biopsy. Before biopsy, sample was collected for measurement of the Stockholm3 risk score. Parameters include prostate-specific antigen (PSA), free PSA, KLK2, GDF15, PSP94, germline risk (single-nucleotide polymorphisms), age, family history, and previous negative biopsy. The primary endpoint was detection of International Society of Urological Pathology (ISUP) Grade ≥2 cancer (clinically significant PCa, csPC). The two primary aims were to (1) demonstrate noninferior sensitivity (0.8 lower bound 95% CI noninferiority margin) in detecting csPC using Stockholm3 compared with PSA (relative sensitivity) and (2) demonstrate superior specificity by reducing biopsies with benign results or low-grade cancers (relative specificity). RESULTS: A total of 2,129 biopsied participants were included: Asian (16%, 350), Black or African American (Black; 24%, 505), Hispanic or Latino and White (Hispanic; 14%, 305), and non-Hispanic or non-Latino and White (White; 46%, 969). Overall, Stockholm3 showed noninferior sensitivity compared with PSA ≥4 ng/mL (relative sensitivity: 0.95 [95% CI, 0.92 to 0.99]) and nearly three times higher specificity (relative specificity: 2.91 [95% CI, 2.63 to 3.22]). Results were consistent across racial and ethnic subgroups: noninferior sensitivity (0.91-0.98) and superior specificity (2.51-4.70). Compared with PSA, Stockholm3 could reduce benign and ISUP 1 biopsies by 45% overall and between 42% and 52% across racial and ethnic subgroups. CONCLUSION: In a substantially diverse population, Stockholm3 significantly reduces unnecessary prostate biopsies while maintaining a similar sensitivity to PSA in detecting csPC.

The Imperative for Population-based Cancer Registration of All Metastatic Cancers.

Metastases are the main cause of morbidity and mortality from solid tumors. Surprisingly, population-based cancer registries in various countries, including the National Cancer Institute's Surveillance, Epidemiology, and End Results program in the United States, only capture data on individuals diagnosed with cancers that are metastatic at diagnosis (M1). Metastatic recurrences of previously diagnosed, initially nonmetastatic tumors are missed. Devasia and colleagues specify an illness-death model for chronic disease and estimate that in prostate cancer, which has a large pool of primary disease that may or may not progress to metastases, about half of all metastatic cancers arise as recurrences from initially nonmetastatic disease. Capturing all incident metastatic cancer cases across all tumor types in population-based cancer registries, not only based on initial stage at diagnosis, would be critical to better understand the disparities in metastatic disease burden and the effectiveness of primary prevention, screening, and therapies for primary and metastatic disease. See related article by Devasia et al., p. 659.

Food Insecurity Is Associated With Dysfunctional Eating Behaviors Among Adults in Puerto Rico.

OBJECTIVE: To examine the association between food insecurity and dysfunctional eating behaviors among adults in Puerto Rico. METHODS: Data from 865 participants were obtained from baseline interviews from the Puerto Rico Observational Study of Psychosocial, Environmental, and Chronic Disease Trends (PROSPECT) cohort. The association between food insecurity and emotional eating (EE) and uncontrolled eating (UE) (categorized as no/moderate/high) was examined using multinomial logistic models. Potential mediation by perceived stress was explored. RESULTS: The prevalence of food insecurity was 20.3%. Compared with adults with food security, adults with food insecurity had higher odds of both moderate EE (odds ratio [OR], 1.91; 95% confidence interval [CI], 1.18-3.09) and high EE (OR, 2.85; 95% CI, 1.75-4.64), and both moderate UE (OR, 1.78; 95% CI, 0.91-3.50) and high UE (OR, 3.28; 95% CI, 1.70-6.33). Perceived stress slightly attenuated these associations. CONCLUSIONS AND IMPLICATIONS: Food insecurity was associated with a higher likelihood of engaging in dysfunctional eating behaviors. Interventions alleviating food insecurity or stress might help adults sustain healthy eating behaviors.

Addition of a Genetic Risk Score for Identification of Men with a Low Prostate-specific Antigen Level in Midlife at Risk of Developing Lethal Prostate Cancer.

Men with a low prostate-specific antigen (PSA) level (<1 ng/ml) in midlife may extend the rescreening interval (if aged 40-59 yr) or forgo future PSA screening (if aged >60 yr) owing to their low risk of aggressive prostate cancer (PCa). However, there is a subset of men who develop lethal PCa despite low baseline PSA. We investigated how a PCa polygenic risk score (PRS) in addition to baseline PSA impacts the prediction of lethal PCa among 483 men aged 40-70 yr from the Physicians' Health Study followed over a median of 33 yr. We examined the association of the PRS with the risk of lethal PCa (lethal cases vs controls) using logistic regression adjusted for baseline PSA. The PCa PRS was associated with risk of lethal PCa (odds ratio per 1 standard deviation in PRS [OR] 1.79, 95% confidence interval [CI] 1.28-2.49). The association between the PRS and lethal PCa was stronger for those with PSA <1 ng/ml (OR 2.23, 95% CI 1.19-4.21) than for men with PSA ≥1 ng/ml (OR 1.61, 95% CI 1.07-2.42). Our PCa PRS improved the identification of men with PSA <1 ng/ml at greater risk of future lethal PCa who should consider ongoing PSA testing. Patient summary: A subset of men develop fatal prostate cancer despite having low prostate-specific antigen (PSA) levels in middle age. A risk score based on multiple genes can help in predicting men who may be at risk of developing lethal prostate cancer and who should be advised to have regular PSA measurements.

A Healthy Lifestyle in Men at Increased Genetic Risk for Prostate Cancer.

BACKGROUND: Prostate cancer is the most heritable cancer. There is a need to identify possible modifiable factors for men at an increased risk of prostate cancer due to genetic factors. OBJECTIVE: To examine whether men at an increased genetic risk of prostate cancer can offset their risk of disease or disease progression by adhering to a healthy lifestyle. DESIGN, SETTING, AND PARTICIPANTS: We prospectively followed 12 411 genotyped men in the Health Professionals Follow-up Study (1993-2019) and the Physicians' Health Study (1983-2010). Genetic risk of prostate cancer was quantified using a polygenic risk score (PRS). A healthy lifestyle was defined by healthy weight, vigorous physical activity, not smoking, and a healthy diet. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall and lethal prostate cancer events (metastatic disease/prostate cancer-specific death) were analyzed using time-to-event analyses estimating hazard ratios (HRs) and lifetime risks. RESULTS AND LIMITATIONS: During 27 yr of follow-up, 3005 overall prostate cancer and 435 lethal prostate cancer events were observed. The PRS enabled risk stratification not only for overall prostate cancer, but also for lethal disease with a four-fold difference between men in the highest and lowest quartiles (HR, 4.32; 95% confidence interval [CI], 3.16-5.89). Among men in the highest PRS quartile, adhering to a healthy lifestyle was associated with a decreased rate of lethal prostate cancer (HR, 0.55; 95% CI, 0.36-0.86) compared with having an unhealthy lifestyle, translating to a lifetime risk of 1.6% (95% CI, 0.8-3.1%) among the healthy and 5.3% (95% CI, 3.6-7.8%) among the unhealthy. Adhering to a healthy lifestyle was not associated with a decreased risk of overall prostate cancer. CONCLUSIONS: Our findings suggest that a genetic predisposition for prostate cancer is not deterministic for a poor cancer outcome. Maintaining a healthy lifestyle may provide a way to offset the genetic risk of lethal prostate cancer. PATIENT SUMMARY: This study examined whether the genetic risk of prostate cancer can be attenuated by a healthy lifestyle including a healthy weight, regular exercise, not smoking, and a healthy diet. We observed that adherence to a healthy lifestyle reduced the risk of metastatic disease and prostate cancer death among men at the highest genetic risk. We conclude that men at a high genetic risk of prostate cancer may benefit from adhering to a healthy lifestyle.

Genetic Risk Prediction for Prostate Cancer: Implications for Early Detection and Prevention.

CONTEXT: Prostate cancer (PCa) is a leading cause of death and partially heritable. Genetic risk prediction might be useful for strategies to reduce PCa mortality through early detection and prevention. OBJECTIVE: To review evidence for genetic risk prediction for PCa. EVIDENCE ACQUISITION: A collaborative literature review was conducted using PubMed and Google Scholar. Search terms included genetic, risk, prediction, and "prostate cancer". Articles addressing screening, early detection, or prevention were prioritized, as were studies involving diverse populations. EVIDENCE SYNTHESIS: Rare pathogenic mutations (RPMs), especially in DNA damage repair genes, increase PCa risk. RPMs in BRCA2 are most clearly deleterious, conferring 2-8.6 times higher risk of PCa and a higher risk of aggressive disease. Common genetic variants can be combined into genetic risk scores (GRSs). A high GRS (top 20-25% of the population) confers two to three times higher risk of PCa than average; a very high GRS (top 1-5%) confers six to eight times higher risk. GRSs are not specific for aggressive PCa, possibly due to methodological limitations and/or a field effect of an elevated risk for both low- and high-grade PCa. It is challenging to disentangle genetics from structural racism and social determinants of health to understand PCa racial disparities. GRSs are independently associated with a lethal PCa risk after accounting for family history and race/ancestry. Healthy lifestyle might partially mitigate the risk of lethal PCa. CONCLUSIONS: Genetic risk assessment is becoming more common; implementation studies are needed to understand the implications and to avoid exacerbating healthcare disparities. Men with a high genetic risk of PCa can reasonably be encouraged to adhere to a healthy lifestyle. PATIENT SUMMARY: Prostate cancer risk is inherited through rare mutations and through the combination of hundreds of common genetic markers. Some men with a high genetic risk (especially BRCA2 mutations) likely benefit from early screening for prostate cancer. The risk of lethal prostate cancer can be reduced through a healthy lifestyle.