Associations of Urban Blue and Green Spaces With Coronary Artery Calcification in Black Individuals and Disadvantaged Neighborhoods.

BACKGROUND: Proximity to urban blue and green spaces has been associated with improved cardiovascular health; however, few studies have examined the role of race and socioeconomic status in these associations. METHODS: Data were from the CARDIA study (Coronary Artery Risk Development in Young Adults). We included longitudinal measurements (1985-1986 to 2010-2011) of blue and green spaces, including percentage of blue space cover, distance to the nearest river, green space cover, and distance to the nearest major park. Presence of coronary artery calcification (CAC) was measured with noncontrast cardiac computed tomography in 2010 to 2011. The associations of blue and green spaces with CAC were assessed with generalized estimating equation regression with adjustment for demographics, individual and neighborhood socioeconomic status, health-related behaviors, and other health conditions. We conducted stratified analyses by race and neighborhood deprivation score to investigate whether the association varied according to social determinants of health. RESULTS: The analytic sample included 1365 Black and 1555 White participants with a mean±SD age of 50.1±3.6 years. Among Black participants, shorter distance to a river and greater green space cover were associated with lower odds of CAC (per interquartile range decrease [1.45 km] to the river: odds ratio [OR], 0.90 [95% CI, 0.84-0.96]; per 10%-point increase of green space cover: OR, 0.85 [95% CI, 0.75-0.95]). Among participants in deprived neighborhoods, greater green space cover was associated with lower odds of CAC (per a 10%-point increase: OR, 0.89 [95% CI, 0.80-0.99]), whereas shorter distance to the park was associated with higher odds of CAC (per an interquartile range decrease [5.3 km]: OR, 1.07 [95% CI, 1.00-1.15]). Black participants in deprived neighborhoods had lower odds of CAC with shorter distance to a river (per an interquartile range decrease: OR, 0.90 [95% CI, 0.82-0.98]) and greater green space cover (per a 10%-point increase: OR, 0.85 [95% CI, 0.75-0.97]). There was no statistical interaction between the blue and green spaces and race or neighborhood characteristics in association with CAC. CONCLUSIONS: Longitudinally, shorter distance to a river and greater green space cover were associated with less CAC among Black participants and those in deprived neighborhoods. Shorter distance to a park was associated with increased odds of CAC among participants in deprived neighborhoods. Black participants residing in more deprived neighborhoods showed lower odds of CAC in association with greater exposure to river and green space cover.

Association of Adverse Childhood Experiences With Accelerated Epigenetic Aging in Midlife.

Importance: Adverse childhood experiences (ACEs) are associated with the risk of poorer health, and identifying molecular mechanisms may lay the foundation for health promotion in people with ACEs. Objective: To investigate the associations of ACEs with changes in epigenetic age acceleration (EAA), a biomarker associated with various health outcomes in middle-aged adults, in a population with balanced race and sex demographics. Design, Setting, and Participants: Data for this cohort study were from the Coronary Artery Risk Development in Young Adults (CARDIA) study. Participants in CARDIA underwent 8 follow-up exams from baseline (year 0 [Y0]; 1985-1986) to Y30 (2015-2016), and participant blood DNA methylation information was obtained at Y15 (2000-2001) and Y20 (2005-2006). Individuals from Y15 and Y20 with available DNA methylation data and complete variables for ACEs and covariates were included. Data were analyzed from September 2021 to August 2022. Exposures: Participant ACEs (general negligence, emotional negligence, physical violence, physical negligence, household substance abuse, verbal and emotional abuse, and household dysfunction) were obtained at Y15. Main Outcomes and Measures: The primary outcome consisted of results from 5 DNA methylation-based EAA measurements known to be associated with biological aging and long-term health: intrinsic EAA (IEAA), extrinsic EAA (EEAA), PhenoAge acceleration (PhenoAA), GrimAge acceleration (GrimAA), and Dunedin Pace of Aging Calculated From the Epigenome (DunedinPACE), measured at Y15 and Y20. Linear regression and generalized estimating equations were used to assess associations of the burden of ACEs (≥4 vs <4 ACEs) with EAA adjusting for demographics, health-related behaviors, and early life and adult socioeconomic status. Results: A total of 895 participants for Y15 (mean [SD] age, 40.4 [3.5] years; 450 males [50.3%] and 445 females [49.7%]; 319 Black [35.6%] and 576 White [64.4%]) and 867 participants for Y20 (mean [SD] age, 45.4 [3.5] years; 432 males [49.8%] and 435 females [50.2%]; 306 Black [35.3%] and 561 White [64.7%]) were included after excluding participants with missing data. There were 185 participants with (20.7%) vs 710 participants without (79.3%) 4 or more ACEs at Y15 and 179 participants with (20.6%) vs 688 participants without (79.4%) 4 or more ACEs at Y20. Having 4 or more ACEs was positively associated with EAA in years at Y15 (EEAA: ß = 0.60 years; 95% CI, 0.18-1.02 years; PhenoAA: ß = 0.62 years; 95% CI = 0.13-1.11 years; GrimAA: ß = 0.71 years; 95% CI, 0.42-1.00 years; DunedinPACE: ß = 0.01; 95% CI, 0.01-0.02) and Y20 (IEAA: ß = 0.41 years; 95% CI, 0.05-0.77 years; EEAA: ß = 1.05 years; 95% CI, 0.66-1.44 years; PhenoAA: ß = 0.57 years; 95% CI, 0.08-1.05 years; GrimAA: ß = 0.57 years; 95% CI, 0.28-0.87 years; DunedinPACE: ß = 0.01; 95% CI, 0.01-0.02) after adjusting for demographics, health-related behaviors, and socioeconomic status. Conclusions and Relevance: In this cohort study, ACEs were associated with EAA among middle-aged adults after controlling for demographics, behavior, and socioeconomic status. These findings of the associations between early life experience and the biological aging process in midlife may contribute to health promotion in a life course perspective.

Inequalities in urban greenness and epigenetic aging: Different associations by race and neighborhood socioeconomic status.

Slower epigenetic aging is associated with exposure to green space (greenness); however, the longitudinal relationship has not been well studied, particularly in minority groups. We investigated the association between 20-year exposure to greenness [Normalized Difference Vegetation Index (NDVI)] and epigenetic aging in a large, biracial (Black/white), U.S. urban cohort. Using generalized estimating equations adjusted for individual and neighborhood socioeconomic characteristics, greater greenness was associated with slower epigenetic aging. Black participants had less surrounding greenness and an attenuated association between greenness and epigenetic aging [ßNDVI5km: -0.80, 95% confidence interval (CI): -4.75, 3.13 versus ßNDVI5km: -3.03, 95% CI: -5.63, -0.43 in white participants]. Participants in disadvantaged neighborhoods showed a stronger association between greenness and epigenetic aging (ßNDVI5km: -3.36, 95% CI: -6.65, -0.08 versus ßNDVI5km: -1.57, 95% CI: -4.12, 0.96 in less disadvantaged). In conclusion, we found a relationship between greenness and slower epigenetic aging, and different associations by social determinants of health such as race and neighborhood socioeconomic status.

Genome-wide DNA methylation association study of recent and cumulative marijuana use in middle aged adults.

Marijuana is a widely used psychoactive substance in the US and medical and recreational legalization has risen over the past decade. Despite the growing number of individuals using marijuana, studies investigating the association between epigenetic factors and recent and cumulative marijuana use remain limited. We therefore investigated the association between recent and cumulative marijuana use and DNA methylation levels. Participants from the Coronary Artery Risk Development in Young Adults Study with whole blood collected at examination years (Y) 15 and Y20 were randomly selected to undergo DNA methylation profiling at both timepoints using the Illumina MethylationEPIC BeadChip. Recent use of marijuana was queried at each examination and used to estimate cumulative marijuana use from Y0 to Y15 and Y20. At Y15 (n = 1023), we observed 22 and 31 methylation markers associated (FDR P ≤ 0.05) with recent and cumulative marijuana use and 132 and 16 methylation markers at Y20 (n = 883), respectively. We replicated 8 previously reported methylation markers associated with marijuana use. We further identified 640 cis-meQTLs and 198 DMRs associated with recent and cumulative use at Y15 and Y20. Differentially methylated genes were statistically overrepresented in pathways relating to cellular proliferation, hormone signaling, and infections as well as schizophrenia, bipolar disorder, and substance-related disorders. We identified numerous methylation markers, pathways, and diseases associated with recent and cumulative marijuana use in middle-aged adults, providing additional insight into the association between marijuana use and the epigenome. These results provide novel insights into the role marijuana has on the epigenome and related health conditions.

Lack of Association of C677T Methylenetetrahydrofolate Reductase Polymorphism with Breast Cancer Risk in Mali.

Methylenetetrahydrofolate reductase (MTHFR) plays a major role in the metabolism of folates and homocysteine, which in turn can affect gene expression and ultimately promote the development of breast cancer. Thus, mutations in the MTHFR gene could influence homocysteine, methionine, and S-adenosylmethionine levels and, indirectly, nucleotide levels. Imbalance in methionine and S-adenosylmethionine synthesis affects protein synthesis and methylation. These changes, which affect gene expression, may ultimately promote the development of breast cancer. We therefore hypothesized that such mutations could also play an important role in the occurrence and pathogenesis of breast cancer in a Malian population. In this study, we used the PCR-RFLP technique to identify the different genotypic profiles of the C677T MTHFR polymorphism in 127 breast cancer women and 160 healthy controls. The genotypic distribution of the C677T polymorphism in breast cancer cases was 88.2% for CC, 11.0% for CT, and 0.8% for TT. Healthy controls showed a similar distribution with 90.6% for CC, 8.8% for CT, and 0.6% for TT. We found no statistical association between the C677T polymorphism and breast cancer risk for the codominant models CT and TT (p > 0.05). The same trend was observed when the analysis was extended to other genetic models, including dominant (p = 0.50), recessive (p = 0.87), and additive (p = 0.50) models. The C677T polymorphism of MTHFR gene did not influence the risk of breast cancer in the Malian samples.

Relative contributions of six lifestyle- and health-related exposures to epigenetic aging: the Coronary Artery Risk Development in Young Adults (CARDIA) Study.

BACKGROUND: DNA methylation-based GrimAge acceleration (GrimAA) is associated with a wide range of age-related health outcomes including cardiovascular disease. Since DNA methylation is modifiable by external and behavioral exposures, it is important to identify which of these exposures may have the strongest contributions to differences in GrimAA, to help guide potential intervention strategies. Here, we assessed the relative contributions of lifestyle- and health-related components, as well as their collective association, to GrimAA. RESULTS: We included 744 participants (391 men and 353 women) from the Coronary Artery Risk Development in Young Adults (CARDIA) study with blood DNA methylation information at CARDIA Exam Year (Y) 20 (2005-2006, mean age 45.9 years). Six cumulative exposures by Y20 were included in the analysis: total packs of cigarettes, total alcohol consumption, education years, healthy diet score, sleep hours, and physical activity. We used quantile-based g-computation (QGC) and Bayesian kernel machine regression (BKMR) methods to assess the relative contribution of each exposure to a single overall association with GrimAA. We also assessed the collective association of the six components combined with GrimAA. Smoking showed the greatest positive contribution to GrimAA, accounting for 83.5% of overall positive associations of the six exposures with GrimAA (QGC weight = 0.835). The posterior inclusion probability (PIP) of smoking also achieved the highest score of 1.0 from BKMR analysis. Healthy diet and education years showed inverse contributions to GrimAA. We observed a U-shaped pattern in the contribution of alcohol consumption to GrimAA. While smoking was the greatest contributor across sex and race subgroups, the relative contributions of other components varied by subgroups. CONCLUSIONS: Smoking, alcohol consumption, and education showed the highest contributions to GrimAA in our study. Higher amounts of smoking and alcohol consumption were likely to contribute to greater GrimAA, whereas achieved education was likely to contribute to lower GrimAA. Identifying pertinent lifestyle- and health-related exposures in a context of collective components can provide direction for intervention strategies and suggests which components should be the primary focus for promoting younger GrimAA.

Accelerated Epigenetic Age Among Women with Invasive Cervical Cancer and HIV-Infection in Nigeria.

Background: Invasive cervical cancer (ICC) is a serious public health burden in Nigeria, where human immunodeficiency virus (HIV) remains highly prevalent. Previous research suggested that epigenetic age acceleration (EAA) could play a role in detection of HIV-associated ICC. However, little research has been conducted on this topic in Africa where the population is most severely affected by HIV-associated ICC. Here, we investigated the association between ICC and EAA using cervical tissues of ICC-diagnosed Nigerian women living with HIV. Methods: We included 116 cervical tissue samples from three groups of Nigerian women in this study: (1) HIV+/ICC+ (n = 39); (2) HIV+/ICC- (n = 53); and (3) HIV-/ICC + (n = 24). We utilized four DNA methylation-based EAA estimators; IEAA, EEAA, GrimAA, and PhenoAA. We compared EAA measurements across the 3 HIV/ICC groups using multiple linear regression models. We also compared EAA between 26 tumor tissues and their surrounding normal tissues using paired t-tests. We additionally performed a receiver operating characteristics (ROC) curve analysis to illustrate the area under the curve (AUC) of EAA in ICC. Results: We found the most striking associations between HIV/ICC status and PhenoAge acceleration (PhenoAA). Among HIV-positive women, PhenoAA was on average 13.4 years higher in women with ICC compared to cancer-free women (P = 0.005). PhenoAA was 20.7 and 7.1 years higher in tumor tissues compared to surrounding normal tissues among HIV-positive women (P = 0.009) and HIV-negative women (P = 0.284), respectively. We did not find substantial differences in PhenoAA between HIV-positive and HIV-negative women with ICC. Conclusion: PhenoAA is associated with ICC in HIV-infected women in our study. Our findings suggest that PhenoAA may serve as a potential biomarker for further risk stratification of HIV-associated ICC in Nigeria and similar resource-constrained settings.

Associations of exposure to metal and metal mixtures with thyroid hormones: Results from the NHANES 2007-2012.

BACKGROUND: Disrupted thyroid homeostasis plays a role in neurocognitive dysfunction and metabolic disorders. Since individuals are exposed to multiple metals simultaneously, it is important to assess the effects of metal mixtures on thyroid hormone status. This study aimed to investigate the associations of metal mixtures and individual metals with thyroid hormone levels. METHODS: Data included 2399 men and 1988 women from the 2007-2012 National Health and Nutrition Examination Survey (2007-2012). Thyroid hormones measured included total triiodothyronine (T3), total thyroxine (T4), free forms of T3 (FT3) and T4 (FT4), and thyroid stimulating hormone (TSH). We included twelve metals (arsenic, barium, cobalt, cesium, molybdenum, antimony, thallium, tungsten, and uranium from urine; cadmium, lead, and mercury from blood) in traditional linear regression models controlling for 12 metals simultaneously and in quantile-based g-computation (QGC) to assess the relative contribution of each metal as well as the overall association with thyroid hormones as a metal mixture. RESULTS: There were associations of the total metal mixture with thyroid hormones for T3 (beta: -0.023, 95% CI: -0.04, -0.01, in women), T4 (beta: -0.03, 95% CI: -0.05, -0.01, in men; beta: -0.026, 95% CI: -0.04, -0.01, in women), and the T3:T4 ratio (beta: 0.026, 95% CI: 0.01, 0.05, in men). Arsenic had negative contributions to T3 and T4. Cadmium had a positive contribution to T4 but negative contributions to T3 and T3:T4. Lead had a positive contribution to T3 and T3:T4, but a negative contribution to T4. CONCLUSION: Multiple metals as a mixture were associated with thyroid hormone levels. Arsenic, cadmium, and lead were individually associated with multiple thyroid hormones. Examination of associations of metal mixtures and individual metals with thyroid hormones can contribute to an understanding of thyroid hormone homeostasis and provide evidence for developing intervention and guidance for health promotion.

DNA Methylation GrimAge and Incident Diabetes: The Coronary Artery Risk Development in Young Adults (CARDIA) Study.

DNA methylation (DNAm)-based biological age (epigenetic age) has been suggested as a useful biomarker of age-related conditions including type 2 diabetes (T2D), and its newest iterations (GrimAge measurements) have shown early promise. In this study, we explored the association between epigenetic age and incident T2D in the context of their relationships with obesity. A total of 1,057 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study were included in the current analyses. We stratified the participants into three groups: normal weight, overweight, and obese. A 1-year increase of GrimAge was associated with higher 10-year (study years 15-25) incidence of T2D (odds ratio [OR] 1.06, 95% CI 1.01-1.11). GrimAge acceleration, which represents the deviation of GrimAge from chronological age, was derived from the residuals of a model of GrimAge and chronological age, and any GrimAge acceleration (positive GrimAA: having GrimAge older than chronological age) was associated with significantly higher odds of 10-year incidence of T2D in obese participants (OR 2.57, 95% CI 1.61-4.11). Cumulative obesity was estimated by years since obesity onset, and GrimAge partially mediated the statistical association between cumulative obesity and incident diabetes or prediabetes (proportion mediated = 8.0%). In conclusion, both older and accelerated GrimAge were associated with higher risk of T2D, particularly among obese participants. GrimAge also statistically mediated the associations between cumulative obesity and T2D. Our findings suggest that epigenetic age measurements with DNAm can potentially be used as a risk factor or biomarker associated with T2D development.

Predictive Risk Factors for Continued Smoking after the Diagnosis of a Genitourinary Malignancy.

OBJECTIVE: To determine risk factors for continued smoking following a diagnosis of a genitourinary (GU) malignancy. Smoking is a well established risk factor in the development of cancers involving the GU tract. Unfortunately, a large percentage of patients continue to smoke or relapse after cancer diagnosis; by doing so, there is an increased risk of recurrence, poor survival rates, treatment complications, secondary primary cancers, and other chronic smoking related illnesses. MATERIALS AND METHODS: Two hundred and five patients who presented to a Urologic Oncology clinic at a single tertiary treatment center were given smoking cessation counseling and pharmacotherapy, as well as a questionnaire which was used to identify smoking status, demographics, and behavioral/psychosocial characteristics. Patients were followed for a minimum of 1 year with a median length of follow up for 13 months. RESULTS: 91% of patients enrolled in the study continued smoking at survey completion. After accounting for age, ethnicity, education and cigarettes consumed/day, 5 variables were independently associated with an increased risk of continued smoking: smoking 20 or more cigarettes per day, less than 2 prior quit attempts, anxiety and/or depression, fear of cancer recurrence, and home secondhand smoke exposure. CONCLUSION: The role of the urologist is imperative for encouraging smoking cessation. While every patient should receive adequate counseling regarding smoking at the time of a GU malignancy diagnosis, identifying patients with the risk factors noted in this study and augmenting smoking cessation efforts may result in stronger efforts to quit and prevention of long-term complications.

Pre-diagnostic carbohydrate intake and treatment failure after radical prostatectomy for early-stage prostate cancer.

PURPOSE: An association between dietary carbohydrate intake and prostate cancer (PCa) prognosis is biologically plausible, but data are scarce. This prospective cohort study examined the relation between pre-diagnostic carbohydrate intake and treatment failure following radical prostatectomy for clinically early-stage PCa. METHODS: We identified 205 men awaiting radical prostatectomy and assessed their usual dietary intake of carbohydrates using the 110-item Block food frequency questionnaire. We also evaluated carbohydrate intake quality using a score based on the consumption of sugars relative to fiber, fat, and protein. Logistic regression analyzed their associations with the odds of treatment failure, defined as a detectable and rising serum prostate-specific antigen (PSA) or receiving androgen deprivation therapy (ADT) within 2 years. RESULTS: Sucrose consumption was associated with a higher odds and fiber consumption with a lower odds of ADT after accounting for age, race/ethnicity, body mass index, and tumor characteristics (odds ratio [OR] (95% confidence interval [CI]) 5.68 (1.71, 18.9) for 3rd vs. 1st sucrose tertile and 0.88 (0.81, 0.96) per gram of fiber/day, respectively). Increasing carbohydrate intake quality also associated with a lower odds of ADT (OR (95% CI) 0.78 (0.66, 0.92) per unit increase in score, range 0-12). CONCLUSIONS: Pre-diagnostic dietary carbohydrate intake composition and quality influence the risk of primary treatment failure for early-stage PCa. Future studies incorporating molecular aspects of carbohydrate metabolism could clarify possible underlying mechanisms.

Colorectal cancer susceptibility loci and influence on survival.

Genome-wide association studies (GWAS) have identified multiple single-nucleotide polymorphisms (SNPs) associated with colorectal cancer risk. To evaluate the potential influence of colorectal cancer susceptibility SNPs on disease prognosis, we investigated whether GWAS-identified colorectal cancer risk SNPs and polygenic risk scores (PRSs) might be associated with survival among colorectal cancer patients. A total of 1374 colorectal cancer patients were recruited from the Korean National Cancer Center. For genotyping, 30 colorectal cancer-susceptibility SNPs previously identified by GWAS were selected. The Cox proportional hazard model was used to evaluate associations of these risk SNPs and PRSs with disease-free survival (DFS) and overall survival (OS). The prognostic values were compared between genetic and nongenetic models using Harrell's c index. During the follow-up period (median: 88, 91 months for DFS and OS), 570 DFS (41.5%) and 487 OS (35.4%) events were observed. We found that 5 SNPs were significantly associated with DFS or OS among colorectal cancer patients at P < .05: rs10936599 at 3q26.2 (MYNN), rs704017 at 10q22.3 (ZMIZ1-AS1), rs11196172 at 10q25.2 (TCF7L2), rs3802842 at 11q23.1 (COLCA1-2), and rs9929218 at 16q22.1 (CDH1). The PRSs constructed using these 5 SNPs were associated with worse survival (DFS: Ptrend = .02 unweighted PRS, Ptrend = .01 weighted PRS, OS: Ptrend = 3.7 × 10-3 unweighted, Ptrend = .02 weighted PRS). Our results suggest that several colorectal cancer susceptibility SNPs might also be related to survival by influencing disease progression.

Alcohol consumption, body mass index and breast cancer risk by hormone receptor status: Women' Lifestyle and Health Study.

BACKGROUND: We aimed to estimate the effect of alcohol consumption on breast cancer risk and to test whether overweight and obesity modifies this association. METHODS: We included in the analysis 45,233 women enrolled in the Swedish Women's Lifestyle and Health study between 1991 and 1992. Participants were followed for occurrence of breast cancer and death until December 2009. Poisson regression models were used, and analyses were done for overall breast cancer and for estrogen receptor positive or negative (ER+, ER-) and progesterone receptor positive and negative (PR+, PR-) tumors separately. RESULTS: A total of 1,385 breast cancer cases were ascertained during the follow-up period. Overall, we found no statistically significant association between alcohol intake and breast cancer risk after adjustment for confounding, with an estimated relative risk (RR) of 1.01 (95 % CI: 0.98-1.04) for an increment in alcohol consumption of 5 g/day. A statistically significant elevated breast cancer risk associated with higher alcohol consumption was found only among women with BMI ≤25 (RR 1.03, 95 % CI 1.0-1.05 per 5 g/day increase). CONCLUSION: An increase in breast cancer risk with higher alcohol consumption was found for breast cancers in women with a BMI ≤25 kg/m(2).

Association between preoperative C-reactive protein level and colorectal cancer survival: a meta-analysis.

PURPOSE: C-reactive protein (CRP) is widely known as a major nonspecific systemic inflammatory marker. A number of previous studies have suggested that elevated preoperative CRP is associated with poor prognosis in colorectal cancer. We aimed to explore the effects of preoperative CRP on colorectal cancer survival through a meta-analysis. METHODS: A total of 21 studies, including a total of 3934 colorectal cancer patients, were eligible. The multivariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of selected studies were used to assess the summary estimates of the association between preoperative CRP and colorectal cancer survival. RESULTS: The pooled HRs of elevated preoperative CRP for earlier stage patients were 2.04 (95% CI 1.45-2.86) for OS, 4.37 (95% CI 2.63-7.27) for CSS, and 1.88 (95% CI 0.97-3.67) for DFS. The pooled HRs of a higher Glasgow Prognostic Score (GPS)/modified GPS (mGPS) for earlier stage patients were 2.20 (95% CI 1.61-3.02) for OS and 1.80 (95% CI 1.37-2.37) for CSS. The association between elevated preoperative CRP and poor survival was observed in patients with advanced cancer. Elevated CRP and GPS/mGPS were significantly associated with poor survival. CONCLUSION: Preoperative CRP and its related markers, GPS and mGPS, were significantly associated with the survival of colorectal cancer surgery patients. The HRs of GPS and mGPS were highly homogeneous across studies for all survival types. Thus, GPS and mGPS may serve as stable predictors of the survival of colorectal cancer surgery patients.

Lack of effects of peroxisome proliferator-activated receptor gamma genetic polymorphisms on breast cancer risk: a case-control study and pooled analysis.

A growing body of evidence suggests that the peroxisome proliferator-activated receptor-gamma (PPARγ) gene may harbor targets for the chemoprevention of breast cancer. However, it is unclear whether polymorphisms in the PPARγ gene are associated with the susceptibility of breast cancer. We performed a candidate gene association study between PPARγ polymorphisms and breast cancer and a meta-analysis on the association of breast cancer with selected PPARγ variants. Six single nucleotide polymorphisms (SNPs) in the PPARγ gene were analyzed among 456 breast cancer patients and 461 controls from the National Cancer Center in Korea. Association between the polymorphisms and breast cancer risk were assessed using the Cochrane-Armitage test for trend and a multivariate logistic regression model. Two SNPs, rs3856806 and rs1801282, had been previously analyzed, thus enabling us to perform pooled analyses on their associations with breast cancer susceptibility. Our findings from the candidate gene association study showed no association between the PPARγ gene polymorphisms and breast cancer risk. A meta-analysis combining existing studies and our current study also refuted an association of the PPARγ gene with breast cancer. Our findings suggest that the PPARγ gene may not harbor variants that alter breast cancer susceptibility, although a moderate sample size might have precluded a decisive conclusion.

Trends of human papillomavirus-related head and neck cancers in Korea: national cancer registry data.

OBJECTIVES/HYPOTHESIS: The incidence of human papillomavirus (HPV)-positive head and neck cancers (HNCs) is increasing sharply worldwide, while their HPV-negative counterparts are showing a decreased frequency. However, epidemiologic data related to these changes are sparse in Korea, which is rapidly adopting more westernized lifestyles. STUDY DESIGN: Data from the Korea Central Cancer Registry, a nationwide population-based cancer registry, from 1999 to 2009 were retrieved. METHODS: Age-standardized rates (ASRs), their annual percent changes (APC) and male-to-female incidence rate ratios (IRRs) were analyzed and compared between HPV-related and HPV-unrelated primary sites. RESULTS: HPV-related sites (oropharynx) had increased significantly over the period 1999 to 2009 (APC = 2.35%, P = 0.017), particularly in young men (30-59 years, APC = 2.65%, P = 0.031), whereas HPV-unrelated sites such as larynx and hypopharynx decreased markedly in both sexes. Interestingly, tongue cancer was found to have increased gradually (APC = 2.35%, P = 0.003) in both sexes. The male-to-female IRRs and the median age of occurrence remained stable. CONCLUSIONS: Although the cultural and ethnic background differs from the United States, cancers of HPV-related sites are increasing in Korea, whereas cancers of HPV-unrelated sites are decreasing, which is similar to the trends observed in the United States. Greater public awareness in Korea of HPV-related HNCs is therefore warranted.

Association between CASR polymorphisms, calcium intake, and colorectal cancer risk.

AIM: The current study aimed to assess the effect of dietary calcium intake and possible interactions with calcium-sensing receptor (CASR) gene polymorphisms on colorectal cancer risk. METHODS: A total of 420 colorectal cancer cases and 815 controls were included in the analysis. Calcium intake was investigated using a 103 item semi-quantitative food frequency questionnaire, and four single nucleotide polymorphisms (SNPs) within the CASR, rs10934578, rs12485716, rs2270916, and rs4678174, were evaluated. RESULTS: No SNPs were associated with colorectal cancer risk after adjusting for covariates. Overall, no significant effect modification by CASR polymorphisms on the association between calcium intake and colorectal cancer risk were detected. However, all 4 of the polymorphisms within the CASR showed significantly higher odds ratios for association with colorectal cancer risk in the low-calcium-intake group compared to the high-calcium-intake group. In the case of rs2270916, individuals with the CC genotype and low calcium intake showed an increased colorectal cancer risk compared to their counterparts with the TT genotype and high calcium intake (OR = 2.11, 95% CI = 1.27-3.51). CONCLUSIONS: Subjects with lower calcium intake exhibited a higher colorectal cancer risk compared with subjects with the same genotype who had higher calcium intake. Our results suggest that individuals who have low dietary calcium intake should be aware of their increased colorectal cancer risk and prevention strategies.

Unbalanced sample size effect on genome-wide population differentiation studies.

The fixation index (F(ST)) is one of the most widely used measurements of genetic distance between populations. The data set from the international HapMap project has been served as a reference data set for population differentiation studies. F(ST) is commonly used in order to compare the sample data with HapMap data. In this study, however, we show that the use of F(ST) without consideration of sample sizes may mislead the result. In particular, we first demonstrate that F(ST) suffers from imbalance of sample sizes through simulation studies and through the analysis of a large scale Korean genome-wide association data. Then, we propose a modified version of F(ST) which is shown to be more robust to imbalance of sample size. In addition, the chi-square test commonly used for homogeneity test is shown to perform similarly to the modified version of F(ST).

The beneficial effect of leisure-time physical activity on bone mineral density in pre- and postmenopausal women.

Regular exercise and physical activity (PA) are known to be protective factors for maintaining bone mineral density (BMD) and preventing osteoporotic fracture. We investigated the associations between leisure-time PA and BMD in 2,903 premenopausal and 2,267 postmenopausal women in Korea. BMDs of the lumbar spine and femur were measured using dual-energy X-ray absorptiometry. Leisure-time PA levels were assessed by a self-administrated questionnaire, and a total metabolic equivalent (MET) score was obtained. Regardless of menopausal status, performing more than moderate levels of leisure-time PA or total MET score had a significant positive association with BMD at both the lumbar spine and femur. In the premenopausal group, women whose total MET score was 1,050-1,500 (MET-min/week) appeared to have the highest lumbar spine and femoral BMD (p < 0.001). The associations between PA level and lumbar spine and femoral BMD were also shown in the postmenopausal group (p < 0.001). In addition, we found dose-response relationships between increasing exercise level and femoral BMD in both the premenopausal and postmenopausal groups. Our results indicate that a more than moderate level of leisure-time PA plays a role in maintaining BMD.

Polymorphisms in adiposity-related genes are associated with age at menarche and menopause in breast cancer patients and healthy women.

STUDY QUESTION: Is there any effect of genetic polymorphisms in adiposity-related genes on the timing of menarche and menopause and the total duration of menstruation among Korean women? SUMMARY ANSWER: Our results suggest that the adiposity-related genes LEP, LEPR and PPARγ may play a role in the onset and cessation of menstruation, and the total duration of menstruation. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: Previous candidate-gene approaches have mainly presented the results for genes related to the estrogen metabolism pathway. Most genes of interest that participate in steroid-hormone metabolism, such as estrogen receptor α and estrogen receptor ß, have been associated with age at menarche and menopause. This study shows the possibility that adiposity-related genes also influence the duration of menstruation. PARTICIPANTS AND SETTING: We recruited 400 breast cancer patients and 452 healthy participants from a case-control study at the Center for Breast Cancer, National Cancer Center in Korea. Ten single nucleotide polymorphisms (SNPs) in the leptin (LEP), leptin receptor (LEPR) and peroxisome proliferator-activated receptor gamma (PPARγ) genes were investigated to evaluate their possible effects on menstruation. Associations between SNPs and age at menarche, age at menopause and duration of menstruation were evaluated. MAIN RESULTS: Four SNPs (rs2167270 of LEP, rs7602 of LEPR and rs4684846 and rs3856806 of PPARγ) were associated with late menarche (≥ 17-year-old). Four SNPs (rs2167270 of LEP and rs1801282, rs2120825, and rs3856806 of PPARγ) were associated with early menopause (<40-year-old) among post-menopausal women. In logistic regression models with covariate adjustment, women with the GG genotype of rs7602 (LEPR) had a higher risk for late menarche [odds ratio (OR) = 1.83, 95% confidence interval (CI) = 1.01-3.31] compared with their counterparts carrying the GA or AA genotypes. In addition, the GG genotype of rs2167270 (LEP) was inversely associated with a duration of menstruation of <30 years (OR = 0.59, 95% CI = 0.31-1.00) compared with the GA or AA genotypes. BIAS, LIMITATIONS AND GENERALIZABILITY TO OTHER POPULATIONS: We obtained information on the age at menarche and menopause from self-administered questionnaires, and some participants might have had difficulty in remembering their age at menarche and menopause. However, this is a non-differential misclassification and should not appreciably affect the interpretation of the results of this study.