Knee osteoarthritis and time-to all-cause mortality in six community-based cohorts: an international meta-analysis of individual participant-level data.

BACKGROUND: Osteoarthritis (OA) is a chronic joint disease, with increasing global burden of disability and healthcare utilisation. Recent meta-analyses have shown a range of effects of OA on mortality, reflecting different OA definitions and study methods. We seek to overcome limitations introduced when using aggregate results by gathering individual participant-level data (IPD) from international observational studies and standardising methods to determine the association of knee OA with mortality in the general population. METHODS: Seven community-based cohorts were identified containing knee OA-related pain, radiographs, and time-to-mortality, six of which were available for analysis. A two-stage IPD meta-analysis framework was applied: (1) Cox proportional hazard models assessed time-to-mortality of participants with radiographic OA (ROA), OA-related pain (POA), and a combination of pain and ROA (PROA) against pain and ROA-free participants; (2) hazard ratios (HR) were then pooled using the Hartung-Knapp modification for random-effects meta-analysis. FINDINGS: 10,723 participants in six cohorts from four countries were included in the analyses. Multivariable models (adjusting for age, sex, race, BMI, smoking, alcohol consumption, cardiovascular disease, and diabetes) showed a pooled HR, compared to pain and ROA-free participants, of 1.03 (0.83, 1.28) for ROA, 1.35 (1.12, 1.63) for POA, and 1.37 (1.22, 1.54) for PROA. DISCUSSION: Participants with POA or PROA had a 35-37% increased association with reduced time-to-mortality, independent of confounders. ROA showed no association with mortality, suggesting that OA-related knee pain may be driving the association with time-to-mortality. FUNDING: Versus Arthritis Centre for Sport, Exercise and Osteoarthritis and Osteoarthritis Research Society International.

Diabetes and cardiovascular disease mortality among a population-based cohort of women with and without breast cancer.

PURPOSE: We investigated whether the relationship between diabetes and all-cause and CVD-related mortality differed between women with and without breast cancer among a cohort drawn from the same source population. METHODS: We interviewed 1,363 women newly diagnosed with breast cancer in 1996-1997, and 1,358 age-matched women without breast cancer, to assess history of physician-diagnosed diabetes. All-cause (n = 631) and CVD-specific mortality (n = 234) was determined by the National Death Index through 2009. We estimated multivariable-adjusted hazard ratios (HRs) for the rates of all-cause and CVD-specific mortality and, to account for competing causes of death, and subdistribution HRs (sHRs) for risk of CVD-related death. RESULTS: Among women with and without breast cancer, respectively, diabetes was associated with: all-cause mortality [HR (95% CI) 1.52 (1.13, 2.05) and 2.17 (1.46, 3.22)]; CVD-specific deaths [1.74 (1.06, 2.84) and 2.06 (1.11, 3.84)]; and risk of CVD-related death [sHR 1.36 (0.81, 2.27) and 1.79 (0.94, 3.40)]. Differences in effect estimates between women with and without breast cancer did not reach statistical significance (p-interaction > 0.10). CONCLUSION: We found that the positive association between a history of physician-diagnosed diabetes and risk of all-cause and CVD-related mortality is of similar magnitude among a population-based cohort of women with or without breast cancer.

Genetic polymorphisms of diabetes-related genes, their interaction with diabetes status, and breast cancer incidence and mortality: The Long Island Breast Cancer Study Project.

To examine 143 diabetes risk single nucleotide polymorphisms (SNPs), identified from genome-wide association studies, in association with breast cancer (BC) incidence and subsequent mortality. A population-based sample of Caucasian women with first primary invasive BC (n = 817) and controls (n = 1021) were interviewed to assess diabetes status. Using the National Death Index, women with BC were followed for >18 years during which 340 deaths occurred (139 BC deaths). Genotyping was done using DNA extracted from blood samples. We used unconditional logistic regression to estimate age-adjusted odds ratios and 95% confidence intervals (CIs) for BC incidence, and Cox regression to estimate age-adjusted hazard ratios and CIs for all-cause and BC-specific mortality. Twelve SNPs were associated with BC risk in additive genotype models, at α = 0.05. The top three significant SNPs included SLC30A8-rs4876369 (P = 0.0034), HHEX-rs11187146 (P = 0.0086), and CDKN2A/CDKN2B-rs1333049 (P = 0.0094). Diabetes status modified the associations between rs4876369 and rs2241745 and BC incidence, on the multiplicative interaction scale. Six SNPs were associated with all-cause (CDKAL1-rs981042, P = 0.0032; HHEX-rs1111875, P = 0.0361; and INSR-rs919275, P = 0.0488) or BC-specific (CDKN2A/CDKN2B-rs3218020, P = 0.0225; CDKAL1-rs981042, P = 0.0246; and TCF2/HNF1B-rs3094508, P = 0.0344) mortality in additive genotype models, at α = 0.05. Genetic polymorphisms that increase the risk of developing diabetes may also increase the risk of developing and dying from BC.

Randomized Controlled Trial of a Home-Based Walking Program to Reduce Moderate to Severe Aromatase Inhibitor-Associated Arthralgia in Breast Cancer Survivors.

BACKGROUND: In postmenopausal women diagnosed with breast cancer (BC), most BC tumors are hormone receptor positive and guidelines recommend adjuvant endocrine therapy that includes an aromatase inhibitor (AI). This study investigates the impact of a 6-week, home-based, self-directed walking program on the commonly reported side effect of AI-associated arthralgia (AIAA). MATERIALS AND METHODS: In this phase II trial, consented BC patients were randomized to walking Intervention (n = 31) or Wait List Control (WLC; n = 31). Eligibility criteria included: stage 0-III BC, on AI for at least 4 weeks, ≥3 on a 5-point scale inquiring about joint symptom intensity "at its worst," and exercising ≤150 minutes per week. Outcomes were self-reported joint symptoms and psychosocial measures. Analyses comparing Intervention and WLC groups were conducted on an intention-to-treat basis to assess intervention impact at 6 weeks (postintervention) and at 6-months follow-up. Adjusted means were calculated to assess differences in two groups. RESULTS: In our final sample (n = 62), mean age was 64 years, 74% were white, and 63% had a body mass index of 30 or higher. At postintervention, Intervention group participants reported significantly increased walking minutes per week, reduced stiffness, less difficulty with activities of daily living (ADL), and less perceived helplessness in managing joint symptoms. At 6-months follow-up (postwalking period in both Intervention and WLC), walking minutes per week had decreased significantly; however, improvements in stiffness and difficulty with ADLs were maintained. CONCLUSION: This study adds to the growing evidence base suggesting exercise as a safe alternative or adjunct to medications for the management of AIAA. IMPLICATIONS FOR PRACTICE: Breast cancer survivors whose adjuvant endocrine treatment includes an aromatase inhibitor (AI) often experience the side effect of AI-associated arthralgia (AIAA). This study investigates the impact of a 6-week, home-based, self-directed walking program in the management of AIAA. Compared with Wait List Control, women in the Intervention group reported significantly increased walking minutes per week, reduced stiffness, less difficulty with activities of daily living, and less perceived helplessness in managing joint symptoms. This study adds to the growing evidence base suggesting exercise as a safe alternative or adjunct to medications for the management of AIAA.

Genetic polymorphisms of phase I metabolizing enzyme genes, their interaction with lifetime grilled and smoked meat intake, and breast cancer incidence.

PURPOSE: To examine associations between 22 CYP single nucleotide polymorphisms (SNPs) and breast cancer incidence and their interactions with grilled-smoked meat intake, a source of polycyclic aromatic hydrocarbons. METHODS: White women with first primary in situ or invasive breast cancer (n = 988) and frequency-matched controls (n = 1021) from a population-based study were interviewed to assess lifetime grilled-smoked meat intake. SNPs with minor allele frequencies of greater than 0.05 were selected because of their links to carcinogenesis. We used multivariable unconditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Breast cancer was inversely associated with CYP1A1 rs104C8943 AG + GG genotype (OR = 0.71, 95% CI = 0.50-0.99; vs. AA genotype) and positively associated with CYP1B1 rs10175338 TT genotype (OR = 1.59, 95% CI = 1.12-2.26; vs. GG genotype) and the CYP3A4 rs2242480 CT + TT genotype (OR = 1.25, 95% CI = 1.00-1.56; vs. CC genotype). The sum of the number of "at-risk" alleles for the CYP SNPs was positively associated with breast cancer incidence (4-6 "at-risk" alleles OR = 2.33, 95% CI = 1.37-3.99 vs. 0-1 alleles; PTrend < .01). We observed multiplicative and additive interactions (P < .05) between grilled-smoked meat intake (low vs. high) with CYP1A1 rs1048943 and CYP1B1 rs10175338 SNPs. CONCLUSIONS: Phase I metabolizing enzyme gene SNPs may play a role in breast cancer development and may modify the grilled-smoked meat intake-breast cancer association.

Socioeconomic factors and self-reported health outcomes in African Americans with rheumatoid arthritis from the Southeastern United States: the contribution of childhood socioeconomic status.

BACKGROUND: There is abundant evidence that low socioeconomic status (SES) is associated with worse health outcomes among people with Rheumatoid Arthritis (RA); however, the influence of socioeconomic disadvantage in early life has yet to be studied within that population. METHODS: Data originated from the cross-sectional arm of the Consortium Evaluation of African-Americans with Rheumatoid Arthritis (CLEAR II), which recruited African-Americans with RA from six sites in the Southeastern United States. We used linear regression models to evaluate associations of parental homeownership status and educational level at participant time of birth with participant-reported fatigue (Visual Analog scale, cm), pain (Visual Analog scale, cm), disability (Health Assessment Questionnaire) and helplessness (Rheumatology Attitudes Index), independently of participant homeownership status and educational level. Models included random effects to account for intra-site correlations, and were adjusted for variables identified using backward selection, from: age, disease-duration, sex, medication use, body-mass index, smoking history. RESULTS: Our sample included 516 CLEAR II participants with full data on demographics and covariates. 89% of participants were women, the mean age was 54.7 years and mean disease duration was 10.8 years. In age adjusted models, parental non-homeownership was associated with greater fatigue (ß = 0.75, 95% CI = 0.36-1.14), disability (ß = 0.12, 95% CI = 0.04-0.19) and helplessness (ß = 0.12, 95% CI = 0.03-0.21), independently of participant homeownership and education; parental education had a further small influence on self-reported fatigue (ß = 0.20, 95% CI = 0.15-0.24). CONCLUSIONS: Parental homeownership, and to a small extent parental education, had modest but meaningful relationships with self-reported health among CLEAR II participants.

Organochlorine insecticides DDT and chlordane in relation to survival following breast cancer.

Organochlorine insecticides have been studied extensively in relation to breast cancer incidence, and results from two meta-analyses have been null for late-life residues, possibly due to measurement error. Whether these compounds influence survival remains to be fully explored. We examined associations between organochlorine insecticides [p,p'-DDT (dichlorodiphenyltrichloroethane), its primary metabolite, p,p'-DDE, and chlordane] assessed shortly after diagnosis and survival among women with breast cancer. A population-based sample of women diagnosed with a first primary invasive or in situ breast cancer in 1996-1997 and with available organochlorine blood measures (n = 633) were followed for vital status through 2011. After follow-up of 5 and 15 years, we identified 55 and 189 deaths, of which 36 and 74, respectively, were breast cancer-related. Using Cox regression models, we estimated the multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for lipid-adjusted organochlorine concentrations with all-cause and breast cancer-specific mortality. At 5 years after diagnosis, the highest tertile of DDT concentration was associated with all-cause (HR = 2.19; 95% CI: 1.02, 4.67) and breast cancer-specific (HR = 2.72; 95% CI: 1.04, 7.13) mortality. At 15 years, middle tertile concentrations of DDT (HR = 1.42; 95% CI 0.99, 2.06) and chlordane (HR = 1.42; 95% CI: 0.94, 2.12) were modestly associated with all-cause and breast cancer-specific mortality. Third tertile DDE concentrations were inversely associated with 15-year all-cause mortality (HR = 0.66; 95% CI: 0.44, 0.99). This is the first population-based study in the United States to show that DDT may adversely impact survival following breast cancer diagnosis. Further studies are warranted given the high breast cancer burden and the ubiquity of these chemicals.

Racial differences in associations between baseline patterns of radiographic osteoarthritis and multiple definitions of progression of hip osteoarthritis: the Johnston County Osteoarthritis Project.

BACKGROUND: To identify baseline radiographic features that predict hip osteoarthritis (HOA) progression, and to explore differences in these associations by race. METHODS: Radiographs from the community-based Johnston County OA Project were scored using Kellgren-Lawrence (KL) grade and for presence and location of joint space narrowing (JSN), osteophytes, and subchondral changes. Associations between these features and HOA progression (increase of at least 1 KL grade, interval hip replacement, range of motion [ROM, a reduction of ≥10° in internal rotation], or disability [increase of ≥0.2 in Health Assessment Questionnaire scores], or Any of these) were assessed using logistic regression, adjusting for age, gender, race, hip injury, BMI, education, smoking and follow-up time, accounting for multiple comparisons. Race interactions were assessed and analyses stratified as indicated. RESULTS: The sample (n = 1,422) included 40 % men and 26 % African American (AA) participants, with mean age 61 years and BMI 29 kg/m(2). The baseline frequency of radiographic hip OA (RHOA) between Caucasians and AAs was similar (23 %), although some radiographic features differed. AAs were more likely to have progression defined by ROM or disability or Any progression; Caucasians were more likely to have RHOA progression. JSN, subchondral sclerosis, and medial osteophytes were associated with increased RHOA progression overall; JSN was associated with disability progression only in AAs, while lateral osteophytes were associated with ROM progression only in Caucasians. CONCLUSIONS: AAs and Caucasians exhibited differences in the radiographic presentation and progression patterns of HOA, with AAs reporting progressive pain and disability, while Caucasians had more RHOA progression.

Genetic polymorphisms in DNA repair and oxidative stress pathways may modify the association between body size and postmenopausal breast cancer.

PURPOSE: Obesity is associated with increased bioavailability of estrogen, hyperinsulinemia, and chronic inflammation, all of which may promote tumor growth. Given DNA repair and oxidative stress pathways may work together with these mechanisms to influence carcinogenesis, we hypothesized that genetic variation in these pathways may modify the obesity-postmenopausal breast cancer (BC) association. METHODS: Resources from a population-based case-control study (990 cases and 970 controls) were used to construct logistic regression models. Body mass index (BMI, weight [kilogram]/height [square meter]) was assessed 1 year before reference date. We characterized interactions between BMI and 29 genetic polymorphisms in oxidative stress and DNA repair pathways. RESULTS: Age-adjusted odds ratios (95% confidence intervals) for postmenopausal BC were 1.24 (1.00-1.52) and 1.35 (1.09-1.71) for 25 ≥ BMI < 30 and BMI ≥ 30 kg/m(2), respectively. We observed multiplicative interactions (P ≤ .05) for eight gene polymorphisms in DNA repair and oxidative stress pathways. For example, among MPO variant allele carriers, obesity was associated with a twofold increased risk of postmenopausal BC (2.13 [1.35-3.36]); however, in wild-type homozygotes, the relationship was less pronounced (1.33 [0.93-1.89]). Our findings were no longer significant after Bonferroni correction. CONCLUSIONS: Obesity may be particularly deleterious for postmenopausal BC development in the presence of biologically plausible DNA repair or oxidative stress genotypes.

Post-diagnosis physical activity and survival after breast cancer diagnosis: the Long Island Breast Cancer Study.

Physical activity (PA) is associated with physiological responses thought to beneficially affect survival after breast cancer diagnosis, yet few studies have considered the entire survivorship experience. Effects of post-diagnosis activity on survival were examined in a cohort of 1,423 women diagnosed with in situ or invasive breast cancer in 1996-1997. Subjects were interviewed soon after diagnosis and again after approximately 5 years to assess breast cancer-related factors, including recreational PA before and after diagnosis. Date and cause of death through 2009 were determined from the National Death Index. Adjusted estimates were obtained using proportional hazards regression and a selection model to account for missing data. Survival was improved among women who were highly active after diagnosis (>9.0 MET h/week) compared to inactive women (0 MET h/week) for all-cause [hazard ratio (HR) (95 % credible interval): 0.33 (0.22, 0.48)] and breast cancer-specific mortality [HR: 0.27 (0.15, 0.46)]. The association of PA with overall mortality appeared stronger in the first 2 years after diagnosis [HR: 0.14 (0.03, 0.44)] compared to 2+ years since diagnosis [HR: 0.37 (0.25, 0.55)]. These findings show that post-diagnosis PA is associated with improved survival among women with breast cancer.

Socioeconomic disparities in the health of african americans with rheumatoid arthritis from the southeastern United States.

OBJECTIVE: To examine cross-sectional baseline data from the Consortium for the Longitudinal Evaluation of African Americans with Early Rheumatoid Arthritis registry for the association between socioeconomic status (SES) with clinical and self-report health outcomes. METHODS: We analyzed data on 937 African Americans who provided comprehensive sociodemographic data in addition to self-reported health outcomes. SES measures included educational attainment, homeownership, household income, and occupation. Outcomes included measures of disease activity, joint damage, autoantibody status, and self-reported measures. Multivariable linear, logistic, and zero-inflated Poisson regression models were used to estimate associations of each SES measure with rheumatoid arthritis (RA) outcomes, controlling for sex, age, disease duration, comorbid conditions, body mass index, smoking, methotrexate/leflunomide use, and biologic agent use. RESULTS: The mean age was 54 years, 86% were women, and the mean RA disease duration was 7.8 years. Approximately 24% had less than a high school degree, 56% had a nonprofessional occupation, 75% had a household income ≤$30,000, and 55% were nonhomeowners. In multivariable regression models, significantly increased associations of disease activity measures and self-reported health outcomes were observed with low household income (≤$30,000/year) and nonhomeownership. Education less than high school was primarily associated with self-reported health outcomes. Among participants with disease duration <2 years, associations of SES were confined to self-reported measures. CONCLUSION: Our results indicate significant socioeconomic disparities in self-reported physical and mental health, clinical disease activity measures, and autoantibody status among African Americans with RA not explained by differences in demographics, medication use, and health behaviors.

Chemical exposure and respiratory health of children in an industrial setting.

BACKGROUND: Parental exposures to chemicals, and the interplay between chemical exposures in utero and in infancy leading to respiratory disease in childhood, are not yet fully understood. In this study we investigated the impact of chemical exposures to the parent in occupational settings and to the child in the home and children's respiratory health. METHODS: A cross-sectional study of lung function and respiratory health was conducted in primary school children in the Kwinana industrial area, south of Perth, Western Australia. Respiratory health was assessed using a standardized questionnaire and lung function was measured using the forced oscillation technique before and after inhaling 200 µg of salbutamol. Univariate logistic regression models were used to explore the relationship between the child's respiratory health (asthma, lung function, bronchodilator response) and exposures to ceramics, dry cleaning fluid, electroplating fluid, glues, leather, fabrics, dyes, insecticides, plastics, metal cleaning fluid, petrol, paint, photochemicals, electric wiring, machining, welding, X-rays, cleaning products, nail products, and "other exposures". The impact of cigarette smoking in the home and family history on respiratory health were also investigated. RESULTS: No associations were found between parental occupational exposures or child's exposures in the home and respiratory health. Significant associations were observed between current smoking in the home and cigarette exposure in the first year of life and poor respiratory health in the children. CONCLUSION: We found no strong evidence of main effects of occupational exposures in impairing the respiratory health of primary school-aged children.

Polymorphisms in DNA repair genes, recreational physical activity and breast cancer risk.

The mechanisms driving the inverse association between recreational physical activity (RPA) and breast cancer risk are complex. While exercise is associated with increased reactive oxygen species production it may also improve damage repair systems, particularly those that operate on single-strand breaks including base excision repair (BER), nucleotide excision repair (NER) and mismatch repair (MMR). Of these repair pathways, the role of MMR in breast carcinogenesis is least investigated. Polymorphisms in MMR or other DNA repair gene variants may modify the association between RPA and breast cancer incidence. We investigated the individual and joint effects of variants in three MMR pathway genes (MSH3, MLH1 and MSH2) on breast cancer occurrence using resources from the Long Island Breast Cancer Study Project. We additionally characterized interactions between RPA and genetic polymorphisms in MMR, BER and NER pathways. We found statistically significant multiplicative interactions (p < 0.05) between MSH2 and MLH1, as well as between postmenopausal RPA and four variants in DNA repair (XPC-Ala499Val, XPF-Arg415Gln, XPG-Asp1104His and MLH1-lle219Val). Significant risk reductions were observed among highly active women with the common genotype for XPC (OR = 0.54; 95% CI, 0.36-0.81) and XPF (OR = 0.62; 95% CI, 0.44-0.87), as well as among active women who carried at least one variant allele in XPG (OR = 0.46; 95% CI, 0.29-0.77) and MLH1 (OR = 0.46; 95% CI, 0.30-0.71). Our data show that women with minor alleles in both MSH2 and MLH1 could be at increased breast cancer risk. RPA may be modified by genes in the DNA repair pathway, and merit further investigation.

Polymorphisms in oxidative stress genes, physical activity, and breast cancer risk.

PURPOSE: The mechanisms driving the physical activity-breast cancer association are unclear. Exercise both increases reactive oxygen species production, which may transform normal epithelium to a malignant phenotype, and enhances antioxidant capacity, which could protect against subsequent oxidative insult. Given the paradoxical effects of physical activity, the oxidative stress pathway is of interest. Genetic variation in CAT or antioxidant-related polymorphisms may mediate the physical activity-breast cancer association. METHODS: We investigated the main and joint effects of three previously unreported polymorphisms in CAT on breast cancer risk. We also estimated interactions between recreational physical activity (RPA) and 13 polymorphisms in oxidative stress-related genes. Data were from the Long Island Breast Cancer Study Project, with interview and biomarker data available on 1,053 cases and 1,102 controls. RESULTS: Women with ≥1 variant allele in CAT rs4756146 had a 23 % reduced risk of postmenopausal breast cancer compared with women with the common TT genotype (OR = 0.77; 95 % CI = 0.59-0.99). We observed two statistical interactions between RPA and genes in the antioxidant pathway (p = 0.043 and 0.006 for CAT and GSTP1, respectively). Highly active women harboring variant alleles in CAT rs1001179 were at increased risk of breast cancer compared with women with the common CC genotype (OR = 1.61; 95 % CI, 1.06-2.45). Risk reductions were observed among moderately active women carrying variant alleles in GSTP1 compared with women homozygous for the major allele (OR = 0.56; 95 % CI, 0.38-0.84). CONCLUSIONS: Breast cancer risk may be jointly influenced by RPA and genes involved in the antioxidant pathway, but our findings require confirmation.

The association of diabetes with breast cancer incidence and mortality in the Long Island Breast Cancer Study Project.

PURPOSE: Diabetes has been associated with increased risk of breast cancer in a number of epidemiologic studies, but its effects on survival among women diagnosed with breast cancer have been examined less frequently. Importantly, prior investigations have rarely considered the influence of factors associated with diabetes such as obesity, age at diabetes diagnosis, duration of diabetes, or diabetes treatments. METHODS: We evaluated the effect of self-reported diabetes on breast cancer incidence and mortality in the Long Island Breast Cancer Study Project, which includes 1,447 breast cancer cases and 1,453 controls. Follow-up data for all-cause (n = 395) and 5-year breast cancer-specific mortality (n = 104) through December 2005 were determined for case women from the National Death Index. Adjusted logistic regression and Cox proportional hazards models were used to estimate odds ratios (OR) and hazards ratios (HR), respectively. RESULTS: Postmenopausal women with diabetes were at increased risk of developing breast cancer [OR = 1.35; 95 % confidence interval (CI) = 0.99-1.85], as were those who were not of white race regardless of menopausal status [OR = 3.89; 95 % CI = 1.66-9.11]. Among case women, diabetes was associated with a modestly increased risk of death from all causes [HR = 1.65; 95 % CI = 1.18-2.29], an association that was stronger in women who were obese at breast cancer diagnosis [HR = 2.49; 94 % CI = 1.58-3.93]. In analyses restricted to diabetics, there was no statistically significant effect of duration of diabetes or type of treatment on breast cancer incidence or mortality. CONCLUSIONS: Our findings suggest that diabetes may increase incidence of breast cancer in older women and non-whites, and mortality due to all causes.

Fat or fit: the joint effects of physical activity, weight gain, and body size on breast cancer risk.

BACKGROUND: Although physical activity reduces breast cancer risk, issues critical to providing clear public health messages remain to be elucidated. These include the minimum duration and intensity necessary for risk reduction and the optimal time period for occurrence, as well as subgroup effects, particularly with regard to tumor heterogeneity and body size. METHODS: This study investigated the relationship between recreational physical activity (RPA) and breast cancer risk, in addition to characterizing the joint effects of activity level, weight gain, and body size, through use of a population-based sample of 1504 cases (N = 233 in situ, N = 1271 invasive) and 1555 controls (aged 20-98 years) from the Long Island Breast Cancer Study Project, in Long Island, New York. RESULTS: A nonlinear dose-response association was observed between breast cancer risk and RPA during the reproductive period and after menopause. Women in the third quartile of activity experienced the greatest benefit with an approximate 30% risk reduction for reproductive (odds ratio = 0.67; 95% confidence interval = 0.48-0.94) and postmenopausal activity (odds ratio = 0.70; 95% confidence interval = 0.52-0.95). Little to no difference was observed regarding intensity of activity or hormone receptor status. Joint assessment of RPA, weight gain, and body size revealed that women with unfavorable energy balance profiles were at increased breast cancer risk. A significant multiplicative interaction was observed between RPA and adult weight gain (P = .033). CONCLUSIONS: RPA at any intensity level during the reproductive and postmenopausal years have the greatest benefit for reducing breast cancer risk. Substantial postmenopausal weight gain may eliminate the benefits of regular activity.

Influence of prediagnostic recreational physical activity on survival from breast cancer.

Recreational physical activity (RPA) is associated with a reduced risk of developing breast cancer, but there is limited research on whether prediagnostic RPA influences survival after breast cancer diagnosis or not. We evaluated the association between prediagnostic RPA and risk of death in 1508 women with a first breast cancer diagnosis during 1996 and 1997 in the population-based Long Island Breast Cancer Study Project. A 5-year mortality, through the end of 2002, was assessed using the National Death Index (N=196). An in-person interview was completed shortly after diagnosis to obtain information on lifetime RPA, which was expressed as metabolic equivalent task hours per week (MET-h/week). A lower risk of all-cause death was observed for women who engaged in an average of 9 or more MET-h/week of RPA from menarche to diagnosis compared with women who did not exercise [age-adjusted and BMI adjusted hazard ratio (HR)=0.57; 95% confidence interval (CI)=0.39-0.83], an association that was similar when evaluated according to menopausal status. Compared with women who did not engage in moderate RPA, those who engaged in any moderate intensity lifetime RPA (>0 MET-h/week) were found to have lower all-cause mortality (HR=0.62; 95% CI=0.46-0.84) and breast cancer-specific mortality (HR=0.64; 95% CI=0.43-0.93). Among postmenopausal women, RPA that took place after menopause resulted in a decrease in overall mortality, whereas no association was observed for RPA which took place prior to menopause (for >0 MET-h/week of RPA vs. no RPA, the HR=0.61; 95% CI=0.39-0.94 and HR=1.00; 95% CI=0.65-1.54, respectively). This study provides support that RPA prior to breast cancer diagnosis improves survival.

Associations of educational attainment, occupation and community poverty with knee osteoarthritis in the Johnston County (North Carolina) osteoarthritis project.

INTRODUCTION: The purpose of this study was to examine data from the Johnston County Osteoarthritis (OA) Project for independent associations of educational attainment, occupation and community poverty with tibiofemoral knee OA. METHODS: A cross-sectional analysis was conducted on 3,591 individuals (66% Caucasian and 34% African American). Educational attainment (< 12 years or ≥12 years), occupation (non-managerial or not), and census block group household poverty rate (< 12%, 12 to 25%, > 25%) were examined separately and together in logistic models adjusting for covariates of age, gender, race, body mass index (BMI), smoking, knee injury and occupational activity score. Outcomes were presence of radiographic knee OA (rOA), symptomatic knee OA (sxOA), bilateral rOA and bilateral sxOA. RESULTS: When all three socioeconomic status (SES) variables were analyzed simultaneously, low educational attainment was significantly associated with rOA (odds ratio (OR) = 1.44, 95% confidence interval (CI) 1.20, 1.73), bilateral rOA (OR = 1.43, 95% CI 1.13, 1.81), and sxOA (OR = 1.66, 95% CI 1.34, 2.06), after adjusting for covariates. Independently, living in a community of high household poverty rate was associated with rOA (OR = 1.83, 95% CI 1.43, 2.36), bilateral rOA (OR = 1.56, 95% CI 1.12, 2.16), and sxOA (OR = 1.36, 95% CI 1.00, 1.83). Occupation had no significant independent association beyond educational attainment and community poverty. CONCLUSIONS: Both educational attainment and community SES were independently associated with knee OA after adjusting for primary risk factors for knee OA.

Common genetic variations in the LEP and LEPR genes, obesity and breast cancer incidence and survival.

Obesity is a strong risk factor for breast cancer in postmenopausal women and adverse prognostic indicator regardless of menopausal status. Leptin is an important regulator of adipose tissue mass and has been associated with tumor cell growth. Leptin exerts its effects through interaction with the leptin receptor (LEPR). We investigated whether genetic variations in the leptin (LEP) and LEPR genes are associated with risk of breast cancer, or once diagnosed, with survival. The polymorphisms LEP G-2548A and LEPR Q223R were characterized in population-based study consisting of mostly European-American women. The study examined 1,065 women diagnosed with first, primary invasive breast cancer between 1996 and 1997. Controls were 1,108 women frequency matched to the cases by 5-year age group. A modest increase in risk of developing breast cancer was associated with the LEP -2548AA genotype when compared to the LEP -2548GG genotype (age-adjusted OR = 1.30; 95% CI = 1.01-1.66). This association was stronger among postmenopausal women who were obese (OR = 1.86; 95% CI = 0.95-3.64) although the interaction was of borderline statistical significance (P = 0.07). We found no evidence of an association with polymorphisms of either LEP or LEPR in relation to all-cause or breast cancer-specific mortality among women with breast cancer (mean follow-up time = 66.7 months). The effects of these genotypes on breast cancer risk and mortality did not vary significantly when stratified by menopausal status. In summary, our results show that a common variant in LEP may be associated with the risk of developing breast cancer supporting the hypothesis that leptin is involved in breast carcinogenesis.

PAH-DNA adducts, cigarette smoking, GST polymorphisms, and breast cancer risk.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) may increase breast cancer risk, and the association may be modified by inherited differences in deactivation of PAH intermediates by glutathione S-transferases (GSTs). Few breast cancer studies have investigated the joint effects of multiple GSTs and a PAH biomarker. OBJECTIVE: We estimated the breast cancer risk associated with multiple polymorphisms in the GST gene (GSTA1, GSTM1, GSTP1, and GSTT1) and the interaction with PAH-DNA adducts and cigarette smoking. METHODS: We conducted unconditional logistic regression using data from a population-based sample of women (cases/controls, respectively): GST polymorphisms were genotyped using polymerase chain reaction and matrix-assisted laser desorption/ionization time-of-flight assays (n = 926 of 916), PAH-DNA adduct blood levels were measured by competitive enzyme-linked immunosorbent assay (n = 873 of 941), and smoking status was assessed by in-person questionnaires (n = 943 of 973). RESULTS: Odds ratios for joint effects on breast cancer risk among women with at least three variant alleles were 1.56 [95% confidence interval (CI), 1.13-2.16] for detectable PAH-DNA adducts and 0.93 (95% CI, 0.56-1.56) for no detectable adducts; corresponding odds ratios for three or more variants were 1.18 (95% CI, 0.82-1.69) for ever smokers and 1.44 (95% CI, 0.97-2.14) for never smokers. Neither interaction was statistically significant (p = 0.43 and 0.62, respectively). CONCLUSION: We found little statistical evidence that PAHs interacted with GSTT1, GSTM1, GSTP1, and GSTA1 polymorphisms to further increase breast cancer risk.