Multimorbid Patterns and Cognitive Performance in the Presence of Informative Dropout Among Community-Dwelling Taiwanese Older Adults.

Background and Objectives: Longitudinal studies among older adults often feature elevated dropout rates and multiple chronic conditions. How Taiwanese multimorbid patterns relate to different cognitive domains remains unclear. This study aims to identify sex-specific multimorbid patterns and associate them with cognitive performance while modeling the risk for dropout. Research Design and Methods: A prospective cohort study (2011-19) in Taiwan recruited 449 Taiwanese older adults without dementia. Global and domain-specific cognition were assessed biennially. We used exploratory factor analysis to identify baseline sex-specific multimorbid patterns of 19 self-reported chronic conditions. We utilized a joint model incorporating longitudinal and time-to-dropout data to examine the association between multimorbid patterns and cognitive performance accounting for the informative dropout via the shared random effect. Results: At the end of the study, 324 participants (72.1%) remained in the cohort, with an average annual attrition rate of 5.5%. We found that advanced age, low levels of physical activities, and poor cognition at baseline were associated with increased dropout risks. Besides, 6 multimorbid patterns were identified, labeled Mental, Renal-vascular, and Cancer-urinary patterns in men, and Mental, Cardiometabolic, and Cancer-endocrine patterns in women. For men, as the follow-up time increased, the Mental pattern was associated with poor global cognition and attention; the Renal-vascular pattern was associated with poor executive function. For women, the Mental pattern was associated with poor memory; as follow-up time increased, and Cardiometabolic patterns were related to poor memory. Discussion and Implications: Sex-specific multimorbid patterns identified in the Taiwanese older population showed differences (notably Renal-vascular pattern in men) from patterns found in Western countries and were differentially associated with cognitive impairment over time. When informative dropout is suspected, appropriate statistical methods should be applied.

Vegetarian diet, food substitution, and nonalcoholic fatty liver.

OBJECTIVES: Vegetarian diets have been shown to improve insulin resistance and reduce body weight, but the effects on nonalcoholic fatty liver require further confirmation. We aim to investigate the association between vegetarian diets, major food groups, and nonalcoholic fatty liver, and to compare the degree of liver fibrosis between vegetarians and nonvegetarians in those with fatty liver. MATERIALS AND METHODS: We analyzed cross-sectional data from the Tzu Chi Health Study which included 2127 nonvegetarians and 1273 vegetarians who did not smoke or habitually drink alcohol and had no hepatitis B or hepatitis C. Fatty liver and liver fibrosis were determined using ultrasonography and the nonalcoholic fatty liver disease fibrosis score, respectively. Diet was assessed through a validated food frequency questionnaire. RESULTS: Vegetarian diets were associated with lower odds of fatty liver (odds ratio = 0.79, 95% confidence interval: 0.68-0.91) after adjusting for age, gender, education, history of smoking and alcohol drinking. Adjustment for body mass index (BMI) attenuated the protective association. Vegetarians had less severe fibrosis than nonvegetarians. Replacing a serving of soy with a serving of meat or fish was associated with 12%-13% increased risk, and replacing a serving of whole grains with a serving of refined grains, fruits, and fruit juice was associated with 3%-12% increased the risk of fatty liver. CONCLUSION: Vegetarian diets, replacing meat and fish with soy, and replacing refined carbohydrates with whole grains, may be inversely associated with nonalcoholic fatty liver related to BMI.

The effect of lifestyle on late-life cognitive change under different socioeconomic status.

This study aimed to identify lifestyle factors associated with cognitive change and to explore whether the effect of lifestyle varies by socioeconomic status (SES). Participants aged 65 years and older were recruited from elderly health checkup programs from 2011 to 2013 in Taiwan. Neuropsychological tests, including tests of global cognition, logical memory, executive function, verbal fluency and attention, were administered at baseline (N = 603) and 2 years later (N = 509). After literature review, 9 lifestyle factors and 3 SES indicators were chosen and their effects on cognitive change were evaluated using linear regression adjusting for age, sex, education, APOE ε4 status, and baseline cognitive score. Five lifestyle factors (high vegetable and fish intake, regular exercise, not smoking, and light to moderate alcohol consumption) and 3 SES indicators [annual household income (> 33,333 USD vs. less), occupational complexity (high vs. low mental demanding job), and years of education (> 12 years vs. less)] were found to be protective against cognitive decline (P < 0.1 in any cognitive domains, ß ranging from 0.06 to 0.38). After further adjusting for all the lifestyle and SES factors, fish intake, higher income and occupational complexity remained protective. Significant interactions were found between a healthful lifestyle (defined as having ≥ 3 healthful lifestyle factors) and income on changes of global cognition and verbal fluency (Pinteraction = 0.02 and 0.04). The protective effect of a healthful lifestyle was observed only among participants with lower income in global cognition and logical memory [ß = 0.17, 95% confidence interval (CI) = 0.07-0.26; ß = 0.30, 95% CI = 0.14-0.46]. To the best of our knowledge, this study for the first time explored how the interactions of lifestyle and SES affect cognitive change. Our findings will aid in developing dementia prevention programs and reduce health inequalities.

CHRNA7 Polymorphisms and Dementia Risk: Interactions with Apolipoprotein ε4 and Cigarette Smoking.

α7 nicotinic acetylcholine receptor (α7nAChR, encoded by CHRNA7) is involved in dementia pathogenesis through cholinergic neurotransmission, neuroprotection and interactions with amyloid-ß. Smoking promotes atherosclerosis and increases dementia risk, but nicotine exerts neuroprotective effect via α7nAChR in preclinical studies. No studies explored the gene-gene, gene-environment interactions between CHRNA7 polymorphism, apolipoprotein E (APOE) ε4 status and smoking on dementia risk. This case-control study recruited 254 late-onset Alzheimer's disease (LOAD) and 115 vascular dementia (VaD) cases (age ≥65) from the neurology clinics of three teaching hospitals in Taiwan during 2007-2010. Controls (N = 435) were recruited from health checkup programs and volunteers during the same period. Nine CHRNA7 haplotype-tagging single nucleotide polymorphisms representative for Taiwanese were genotyped. Among APOE ε4 non-carriers, CHRNA7 rs7179008 variant carriers had significantly decreased LOAD risk after correction for multiple tests (GG + AG vs. AA: adjusted odds ratio = 0.29, 95% confidence interval = 0.13-0.64, P = 0.002). Similar findings were observed for carriers of GT haplotype in CHRNA7 block4. A significant interaction was found between rs7179008, GT haplotype in block4 and APOE ε4 on LOAD risk. rs7179008 variant also reduced the detrimental effect of smoking on LOAD risk. No significant association was found between CHRNA7 and VaD. These findings help to understand dementia pathogenesis.

Interplay between Superoxide Dismutase, Glutathione Peroxidase, and Peroxisome Proliferator Activated Receptor Gamma Polymorphisms on the Risk of End-Stage Renal Disease among Han Chinese Patients.

Background. Single nucleotide polymorphisms (SNPs) of antioxidants, including superoxide dismutase 2 (SOD2) and glutathione peroxidase 1 (GPX1), play an important role in the risk for cancer and metabolic disorders. However, little is known regarding the effect of antioxidant SNPs on renal events. Methods. We prospectively enrolled multicenter patients with end-stage renal disease (ESRD) and those without chronic kidney disease (CKD) of Han Chinese origin, with SOD2 (Val16Ala), GPX1 (Pro197Leu), and PPAR-γ (Pro12Ala, C161T) genotyped. Multiple regression analyses were conducted to evaluate the significant risk determinants for ESRD. Results. Compared to ESRD patients, non-CKD subjects were more likely to have T allele at SOD2 Val16Ala (p = 0.036) and CC genotype at PPAR-γ Pro12Ala (p = 0.028). Regression analysis showed that TT genotype of SOD2 Val16Ala conferred significantly lower ESRD risk among patients without diabetes (odds ratio 0.699; p = 0.018). GPX1 SNP alone did not alter the risk. We detected significant interactions between SNPs including PPAR-γ Pro12Ala, C161T, and GPX1 regarding the risk of ESRD. Conclusion. This is the first and largest study on the association between adverse renal outcomes and antioxidant SNPs among Han Chinese population. Determination of SOD2 and PPAR-γ SNPs status might assist in ESRD risk estimation.

Polymorphisms of an innate immune gene, toll-like receptor 4, and aggressive prostate cancer risk: a systematic review and meta-analysis.

BACKGROUND: Toll-like receptor 4 (TLR4) is one of the best known TLR members expressed on the surface of several leukocytes and tissue cells and has a key function in detecting pathogen and danger-associated molecular patterns. The role of TLR4 in the pathophysiology of several age-related diseases is also well recognized, such as prostate cancer (PCa). TLR4 polymorphisms have been related to PCa risk, but the relationship between TLR4 genotypes and aggressive PCa risk has not been evaluated by any systematic reviews. METHODS: We performed a systematic review and meta-analysis of candidate-gene and genome-wide association studies analyzing this relationship and included only white population. Considering appropriate criteria, only nine studies were analyzed in the meta-analysis, including 3,937 aggressive PCa and 7,382 controls. RESULTS: Using random effects model, no significant association was found in the ten TLR4 SNPs reported by at least four included studies under any inheritance model (rs2737191, rs1927914, rs10759932, rs1927911, rs11536879, rs2149356, rs4986790, rs11536889, rs7873784, and rs1554973). Pooled estimates from another ten TLR4 SNPs reported by three studies also showed no significant association (rs10759930, rs10116253, rs11536869, rs5030717, rs4986791, rs11536897, rs1927906, rs913930, rs1927905, and rs7045953). Meta-regression revealed that study type was not a significant source of between-study heterogeneity. CONCLUSIONS: TLR4 polymorphisms were not significantly associated with the risk of aggressive PCa.

Genetic polymorphisms of the glycine N-methyltransferase and prostate cancer risk in the health professionals follow-up study.

PURPOSE: Glycine N-methyltransferase (GNMT) affects genetic stability by regulating the ratio of S-adenosylmethionine to S-adenosylhomocysteine, by binding to folate, and by interacting with environmental carcinogens. In Taiwanese men, GNMT was found to be a tumor susceptibility gene for prostate cancer. However, the association of GNMT with prostate cancer risk in other ethnicities has not been studied. It was recently reported that sarcosine, which is regulated by GNMT, increased markedly in metastatic prostate cancer. We hereby explored the association of GNMT polymorphisms with prostate cancer risk in individuals of European descent from the Health Professionals Follow-up Study (HPFS). METHODS: A total of 661 incident prostate cancer cases and 656 controls were identified from HPFS. The GNMT short tandem repeat polymorphism 1 (STRP1), 4-bp insertion/deletion polymorphisms (INS/DEL) and the single nucleotide polymorphism rs10948059 were genotyped to test for their association with prostate cancer risk. RESULTS: The rs10948059 T/T genotype was associated with a 1.62-fold increase in prostate cancer risk (95% confidence interval (CI): 1.18, 2.22) when compared with the C/C genotype. The STRP1 ≥ 16GAs/≥ 16GAs genotype was associated with decreased risk of prostate cancer when compared with the < 16GAs/< 16GAs genotype (odds ratio (OR) = 0.68; 95% CI: 0.46, 1.01). INS/DEL was not associated with prostate cancer risk. Haplotypes containing the rs10948059 T allele were significantly associated with increased prostate cancer risk. CONCLUSION: In men of European descent, the GNMT rs10948059 and STRP1 were associated with prostate cancer risk. Compared to the study conducted in Taiwanese men, the susceptibility GNMT alleles for prostate cancer had a reverse relationship. This study highlights the differences in allelic frequencies and prostate cancer susceptibility in different ethnicities.

Prospective study of effect modification by Toll-like receptor 4 variation on the association between Trichomonas vaginalis serostatus and prostate cancer.

PURPOSE: In previous studies, we observed a positive association between Trichomonas vaginalis serostatus and risk of prostate cancer, particularly aggressive cancer, which we hypothesized might be due to T. vaginalis-mediated intraprostatic inflammation and cell damage. To explore this hypothesis further, we investigated effect modification by Toll-like receptor 4 (TLR4) variation on this association. We hypothesized that TLR4 variation might serve a marker of the anti-trichomonad immune response because T. vaginalis has been shown to elicit inflammation through this receptor. METHODS: We previously genotyped the non-synonymous TLR4 single nucleotide polymorphism (SNP), rs4986790, and determined T. vaginalis serostatus for 690 incident prostate cancer cases and 692 controls in a nested case-control study within the Health Professionals Follow-up Study. RESULTS: A non-significant suggestion of effect modification was observed by rs4986790 carrier status on the association between T. vaginalis serostatus and prostate cancer risk (p interaction = 0.07). While no association was observed among men homozygous wildtype for this SNP (odds ratio (OR) = 1.23, 95 % confidence interval (CI): 0.86-1.77), a positive association was observed among variant carriers (OR = 4.16, 95 % CI: 1.32-13.1). CONCLUSIONS: Although not statistically significant, TLR4 variation appeared to influence the association between T. vaginalis serostatus and prostate cancer risk consistent with the hypothesis that inflammation plays a role in this association. Larger studies will be necessary to explore this possible effect modification further.

Sequence variants of interleukin 6 (IL-6) are significantly associated with a decreased risk of late-onset Alzheimer's disease.

BACKGROUND: Interleukin 6 (IL-6) has been related to beta-amyloid aggregation and the appearance of hyperphosphorylated tau in Alzheimer's disease (AD) brain. However, previous studies relating IL-6 genetic polymorphisms to AD included few and unrepresentative single nucleotide polymorphisms (SNPs) and the results were inconsistent. METHODS: This is a case-control study. A total of 266 patients with AD, aged≧65, were recruited from three hospitals in Taiwan (2007-2010). Controls (n = 444) were recruited from routine health checkups and volunteers of the hospital during the same period of time. Three common IL-6 haplotype-tagging SNPs were selected to assess the association between IL-6 polymorphisms and the risk of late-onset AD (LOAD). RESULTS: Variant carriers of IL-6 rs1800796 and rs1524107 were significantly associated with a reduced risk of LOAD [(GG + GC vs. CC): adjusted odds ratio (AOR) = 0.64 and (CC + CT vs. TT): AOR = 0.60, respectively]. Haplotype CAT was associated with a decreased risk of LOAD (0 and 1 copy vs. 2 copies: AOR = 0.65, 95% CI = 0.44-0.95). These associations remained significant in ApoE e4 non-carriers only. Hypertension significantly modified the association between rs2069837 polymorphisms and the risk of LOAD (pinteraction = 0.03). CONCLUSIONS: IL-6 polymorphisms are associated with reduced risk of LOAD, especially in ApoE e4 non-carriers. This study identified genetic markers for predicting LOAD in ApoE e4 non-carriers.

Use of germline polymorphisms in predicting concurrent chemoradiotherapy response in esophageal cancer.

PURPOSE: To identify germline polymorphisms to predict concurrent chemoradiation therapy (CCRT) response in esophageal cancer patients. MATERIALS AND METHODS: A total of 139 esophageal cancer patients treated with CCRT (cisplatin-based chemotherapy combined with 40 Gy of irradiation) and subsequent esophagectomy were recruited at the National Taiwan University Hospital between 1997 and 2008. After excluding confounding factors (i.e., females and patients aged ≥70 years), 116 patients were enrolled to identify single nucleotide polymorphisms (SNPs) associated with specific CCRT responses. Genotyping arrays and mass spectrometry were used sequentially to determine germline polymorphisms from blood samples. These polymorphisms remain stable throughout disease progression, unlike somatic mutations from tumor tissues. Two-stage design and additive genetic models were adopted in this study. RESULTS: From the 26 SNPs identified in the first stage, 2 SNPs were found to be significantly associated with CCRT response in the second stage. Single nucleotide polymorphism rs16863886, located between SGPP2 and FARSB on chromosome 2q36.1, was significantly associated with a 3.93-fold increase in pathologic complete response to CCRT (95% confidence interval 1.62-10.30) under additive models. Single nucleotide polymorphism rs4954256, located in ZRANB3 on chromosome 2q21.3, was associated with a 3.93-fold increase in pathologic complete response to CCRT (95% confidence interval 1.57-10.87). The predictive accuracy for CCRT response was 71.59% with these two SNPs combined. CONCLUSIONS: This is the first study to identify germline polymorphisms with a high accuracy for predicting CCRT response in the treatment of esophageal cancer.

Cancer and inflammation: promise for biologic therapy.

Cancers often arise as the end stage of inflammation in adults, but not in children. As such there is a complex interplay between host immune cells during neoplastic development, with both an ability to promote cancer and limit or eliminate it, most often complicit with the host. In humans, defining inflammation and the presence of inflammatory cells within or surrounding the tumor is a critical aspect of modern pathology. Groups defining staging for neoplasms are strongly encouraged to assess and incorporate measures of the presence of apoptosis, autophagy, and necrosis and also the nature and quality of the immune infiltrate. Both environmental and genetic factors enhance the risk of cigarette smoking, Helicobacter pylori, hepatitis B/C, human papilloma virus, solar irradiation, asbestos, pancreatitis, or other causes of chronic inflammation. Identifying suitable genetic polymorphisms in cytokines, cytokine receptors, and Toll-like receptors among other immune response genes is also seen as high value as genomic sequencing becomes less expensive. Animal models that incorporate and assess not only the genetic anlagen but also the inflammatory cells and the presence of microbial pathogens and damage-associated molecular pattern molecules are necessary. Identifying micro-RNAs involved in regulating the response to damage or injury are seen as highly promising. Although no therapeutic strategies to prevent or treat cancers based on insights into inflammatory pathways are currently approved for the common epithelial malignancies, there remains substantial interest in agents targeting COX2 or PPARgamma, ethyl pyruvate and steroids, and several novel agents on the horizon.

Early-life or lifetime sun exposure, sun reaction, and the risk of squamous cell carcinoma in an Asian population.

BACKGROUND: It has been widely accepted that sun exposure is a risk factor of squamous cell carcinoma (SCC) among fair-skinned populations. However, sun exposure and sun reaction have not been explored in Asians and no gender-specific data were available. METHOD: In a case-control study, 176 incident skin cancer cases were recruited from National Cheng-Kung University Medical Center from 1996 to 1999. Controls included 216 age-, gender-, and residency-matched subjects from the southwestern Taiwan. A questionnaire was administered to collect information on life style and other risk factors. Logistic regression analysis was performed to evaluate the association between sun exposure or sun reaction and the risk of SCC by gender. RESULTS: Early-age (age 15 to 24) and lifetime sun exposure were significantly associated with increased risk of SCC in a dose-response pattern [odds ratio (OR) = 1.49-3.08, trend p = 0.009 and 0.0007, respectively]. After stratified by gender, the third tertile of early-age sun exposure was significantly associated with the SCC risk among men (OR = 3.08). The second and third tertiles of lifetime sun exposure was significantly associated with SCC risk among women (OR = 3.78 and 4.53, respectively). Skin reaction after 2-h sun exposure during childhood and adolescence was not significantly associated with the risk of SCC. CONCLUSIONS: Lifetime sun exposure was more related to SCC risk in women, while early-age sun exposure was more relevant to men's SCC risk. This may be attributable to different lifestyle between men and women.

Human papilloma virus and female lung adenocarcinoma.

Lung cancer is the leading cause of cancer among women worldwide, and adenocarcinoma is the most common histological subtype among non-smoking women. Previous studies showed that human papillomavirus (HPV) infection may relate to the tumorigenesis of pulmonary adenocarcinoma. Women with anogenital malignancy have a higher risk of lung cancer, which raises the possibility of HPV transmission from the cervix to the lung. Two postulated pathways are discussed in this work. First, HPV may infect the female cervix and then move to the lung by blood circulation. The second transmission route is the HPV infection of oral cavity resulting from dangerous sexual contacts, and subsequently transmitted to the lung. This chapter also reviews the techniques for detecting the existence, subtypes, and viral load of HPV. Future studies are needed to demonstrate the causal inference between HPV infection and the risk of female lung adenocarcinoma.

Risk factors for dementia.

Dementia is a complex human disease. The incidence of dementia among the elderly population is rising rapidly worldwide. In the United States, Alzheimer's disease (AD) is the leading type of dementia and was the fifth and eighth leading cause of death in women and men aged > or = 65 years, respectively, in 2003. In Taiwan and many other counties, dementia is a hidden health issue because of its underestimation in the elderly population. In Western countries, the prevalence of AD increases from 1-3% among people aged 60-64 years to 35% among those aged > 85 years. In Taiwan, the prevalence of dementia for people aged > or = 65 years was 2-4% by 2000. Therefore, it is important to identify protective and risk factors for dementia to prevent this disease at an early stage. Several factors are related to dementia, e.g. age, ethnicity, sex, genetic factors, physical activity, smoking, drug use, education level, alcohol consumption, body mass index, comorbidity, and environmental factors. In this review, we focus on studies that have evaluated the association between these factors and the risk of dementia, especially AD and vascular dementia. We also suggest future research directions for researchers in dementia-related fields.

Association between sequence variant of c.553 G > T in the apolipoprotein A5 gene and metabolic syndrome, insulin resistance, and carotid atherosclerosis.

Common polymorphism of the apolipoprotein A5 gene (APOA5, c.553G>T) related to metabolic syndrome components, insulin resistance, and carotid atherosclerosis remains unclear. We investigated the associations of the APOA5 c.553G>T gene with various metabolic syndrome components and carotid artery atherosclerosis among family members. A total of 661 participants who provided complete genotyping and carotid artery measures were included in this study. Participants with APOA5 c.553T carrier (GT and TT) were more likely to have higher levels of triglycerides and apolipoprotein B, as well as lower levels of high-density lipoprotein (HDL) cholesterol, than participants with the GG genotype. Individuals who carried T alleles had an increased risk of a high level of triglycerides (multivariate odds ratio [OR], 3.86; 95% confidence interval [CI], 1.98-7.55; P<0.0001) and low levels of HDL cholesterol (OR, 2.32; 95% CI, 1.40-3.86; P=0.0012) compared with those without T alleles. The age was an effect modifier for the association between APOA5 genotype and smoking, alcohol drinking, obesity, and lipid profiles, including total, HDL, and low-density lipoprotein (LDL) cholesterol; triglycerides; and apolipoproteins. In addition, the association between APOA5 genotype and hypertriglyceridemia was significant only in adult groups (OR, 3.53; 95% CI, 1.79-6.94), and the association between APOA5 genotype and low HDL cholesterol was stable in young adolescents (OR, 2.39; 95% CI, 1.19-4.78) and adults (OR, 2.20; 95% CI, 1.17-4.15). Our findings indicated that the APOA5 c.553G>T polymorphism is associated with high triglycerides and low HDL cholesterol but not with other metabolic syndrome components or carotid atherosclerosis in this ethnic Chinese population.

Pediatric empyema: Outcome analysis of thoracoscopic management.

OBJECTIVE: Thoracoscopy has become a favored modality in treating pediatric empyema. However, the factors affecting the outcome of thoracoscopic management remain unclear. In this study, we report our experience using thoracoscopy to treat empyema in pediatric patients and investigate the factors affecting outcome. METHODS: We retrospectively reviewed the demographic data, clinical presentation, radiographic findings, laboratory studies, and hospital course of 101 pediatric patients who underwent thoracoscopy for empyema between 1995 and 2008. RESULTS: Empyema was due to pneumococcus infection in 64 patients (63.4%), and 69% of the cultured microorganisms were penicillin nonsusceptible. Chest computed tomography scan was performed in 96 patients, in whom necrotizing pneumonia was noted in 35 (36.5%). Preoperative intensive care unit admission was required for 33 patients (32.7%). Preoperative chest tube drainage was performed in 36 patients (35.6%), and thoracoscopy was used as the primary treatment in the remaining 65 patients. Complications occurred in 10 patients (9.9%); there were no mortalities. The median postoperative hospital stay was 13 days. Multivariate analyses showed that necrotizing pneumonia was significantly associated with the presence of complications, and that necrotizing pneumonia, preoperative intensive care unit admission, and preoperative chest tube drainage were independent risk factors for a longer postoperative hospital stay. CONCLUSION: The clinical presentations of empyema in children requiring thoracoscopy are diverse. Patients with necrotizing pneumonia and those requiring preoperative intensive care unit admission and undergoing preoperative chest tube drainage are at high risk for developing complications and requiring longer hospital stay after thoracoscopy.

Family history of prostate and breast cancer and the risk of prostate cancer in the PSA era.

BACKGROUND: A family history of prostate cancer (PCa) or breast cancer (BCa) has been associated with the risk of PCa, but the risks were inconsistent in terms of the affected family members, and data in the PSA era are limited. METHODS: This study included a subcohort of the Health Professionals Follow-Up Study composed of a highly PSA screened population from 1986 to 2004 with 3,695 PCa cases identified. Questionnaires and a food frequency questionnaire were administered every other and every 4 years, respectively. Family history of PCa and BCa was ascertained in 1990, 1992, and 1996. All statistics were two-sided. RESULTS: A family history of PCa in both a father and brother(s) was associated with a 2.3-fold increased risk of PCa [95% confidence interval (CI) = 1.76-3.12]. Men with a father or brother(s) with a PCa diagnosis at age<60 and >or=60 had 2.16- and 1.95-fold increased risk of PCa, respectively. A family history of PCa was related to early-onset PCa (<65 years: RR = 2.25, 95% CI = 1.95-2.60) and weakly to late-onset PCa (>or=65 years: RR = 1.67, 95% CI = 1.52-1.85). History of BCa in a mother or a sister was associated with a 1.22-fold increased risk of PCa (95% CI = 1.08-1.38). CONCLUSION: A family history of PCa or BCa significantly increases PCa risk. These associations are evident in a population with widespread PSA screening.

Association between genetic polymorphisms of macrophage scavenger receptor 1 gene and risk of prostate cancer in the health professionals follow-up study.

BACKGROUND: Macrophage scavenger receptor 1 (MSR1) is involved in chronic inflammation, which is a risk factor for prostate cancer. Association studies assessing the relationship between sequence variants of MSR1 and prostate cancer are inconsistent. We hypothesized that sequence variants of MSR1 were associated with prostate cancer risk. METHODS: In a nested case-control design within the Health Professionals Follow-up Study, we identified 700 participants with prostate cancer diagnosed after they had provided a blood specimen in 1993 and before January 2000. Controls were 700 age-matched men without prostate cancer who had had a prostate-specific antigen test after providing a blood specimen. We genotyped three common (>5%) single nucleotide polymorphisms (SNP) that have been reported previously to be associated with risk of prostate cancer. RESULTS: None of these MSR1 SNPs nor estimated haplotypes were associated with prostate cancer risk (P for the global test for haplotypes = 0.89). These MSR1 SNPs also did not appear to be associated with higher-grade or advanced-stage prostate cancer. CONCLUSION: The association between these sequence variants of MSR1 and the risk of prostate cancer was null. Further study of aggressive prostate cancer may be warranted, as we had limited power to assess these.

Sequence variants of elaC homolog 2 (Escherichia coli) (ELAC2) gene and susceptibility to prostate cancer in the Health Professionals Follow-Up Study.

Two non-synonymous single-nucleotide polymorphisms (SNPs), Ser217Leu and Ala541Thr, in the elaC homolog 2 (Escherichia coli) (ELAC2) gene have been related to prostate cancer risk in previous studies, though with inconsistent results. The association of ELAC2 haplotypes with prostate cancer risk has not yet been explored. We assessed whether sequence variants in ELAC2 were associated with the risk of total or aggressive prostate cancer. In a nested case-control design within the Health Professionals Follow-Up Study, we identified 659 participants with prostate cancer diagnosed after they provided a blood specimen in 1993 and before January 2000. Controls were 656 age-matched men without prostate cancer who had had a prostate-specific antigen test after providing a blood specimen. We genotyped eight tagging SNPs in ELAC2 to test for the association between sequence variances in ELAC2 and prostate cancer. No individual SNP (including Ser217Leu) was associated with the risk of prostate cancer. Ala541Thr is a rare SNP in this population. One common haplotype (hap4) was statistically significantly associated with an increased risk of prostate cancer [odds ratio (OR) = 1.39, 95% confidence interval = 1.05-1.85]. Two common promoter SNPs and three common haplotypes were statistically significantly associated with aggressive prostate cancer (carriers versus non-carriers-snp2: OR = 1.43, snp3: OR = 0.69, hap1: OR = 1.47, hap2: OR = 0.72, hap4: OR = 1.51; global P-value for all common haplotypes = 0.11). Common SNPs and haplotypes of ELAC2 were associated with risk of aggressive prostate cancer.