Publications by authors named "Richard N Baumgartner"

82 Publications

Ethnic and biological differences in the association between physical activity and survival after breast cancer.

NPJ Breast Cancer 2020 9;6:51. Epub 2020 Oct 9.

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD USA.

Physical activity is recommended for most cancer patients as a nonpharmacological therapy to improve prognosis. Few studies have investigated the association between physical activity and breast cancer prognosis by ethnicity, biological, and modifiable risk factors for mortality. We investigated the association between physical activity and long-term survival among breast cancer survivors. A total of 397 survivors (96 Hispanic and 301 non-Hispanic White (NHW)) from the New Mexico HEAL study contributed baseline and biological data approximately 6 months after diagnosis. Study outcomes included all-cause, breast cancer-specific, and non-breast cancer mortality. The exposure was self-reported physical activity within the past month. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox Proportional Hazards regression. A total of 133 deaths (53 breast cancer-specific deaths) were observed after a median follow-up time of 13 years. Engaging in >6.9 metabolic equivalent hours/week (MET-h/week) of moderate to vigorous physical activity (active) was inversely associated with all-cause mortality among all women (HR 0.66, 95% CI 0.43-0.99) and NHWs (HR 0.58, 95% CI 0.36-0.94). Active NHW women also had a reduced risk of non-breast cancer mortality (HR 0.56, 95% CI 0.31-0.99), compared to inactive women (0 MET-h/week). In subgroups, we observed the inverse associations with all-cause mortality among women >58 years old (-interaction= 0.03) and with localized stage (-interaction = 0.046). Our results confirm the protective association between physical activity and mortality after breast cancer diagnosis, and demonstrate that this association significantly differs by age and cancer stage. Larger studies are warranted to substantiate our findings.
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http://dx.doi.org/10.1038/s41523-020-00194-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547070PMC
October 2020

Pyoderma Gangrenosum in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

Dig Dis Sci 2020 09 10;65(9):2675-2685. Epub 2020 Jan 10.

Price Institute of Surgical Research, The Hiram C. Polk Jr., MD Department of Surgery, University of Louisville, 550 South Jackson Street, Louisville, KY, 40202, USA.

Background: Pyoderma gangrenosum (PG) is an uncommon but severe extra-intestinal manifestation (EIM) of inflammatory bowel disease (IBD). The incidence and risk factors for PG are disputed.

Aims: To assess the incidence of PG and identify factors associated with PG in IBD patients.

Methods: A search of electronic databases (Ovid and PubMed) was conducted between 1966 and 2019. Studies that calculated the incidence of PG in IBD patient cohorts were included. Patient demographics, IBD subtype, and EIM presence were recorded. A review of our institutional database of 1057 IBD patients was conducted. A multivariate regression model and meta-analysis were conducted to identify risk factors for PG. A random effects model was used to combine the data of included studies.

Results: Fourteen studies were included in addition to 1057 IBD patients and 26 PG cases from the Louisville cohort. In total, there were 379 cases of PG in the cumulative cohort of 61,695 IBD patients. The PG incidence in individual studies ranged from 0.4 to 2.6%. In the institutional cohort, ocular EIMs and a permanent stoma were significant risk factors for PG. In the meta-analysis, PG was associated with female gender (RR = 1.328, 95% CI 1.161-1.520), Crohn's disease (RR = 1.193, 95% CI 1.001-1.422), erythema nodosum (RR = 9.281, 95% CI 6.081-14.164), and ocular EIM (RR = 4.55, 95% CI 3.04-6.81). There was study heterogeneity when assessing IBD subtype, ocular, and joint EIMs.

Conclusions: There are conflicting data on the incidence and risk factors for PG. This meta-analysis confirms an association between PG and female gender, Crohn's disease, erythema nodosum, and ocular EIM that have been described in smaller studies.
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http://dx.doi.org/10.1007/s10620-019-05999-4DOI Listing
September 2020

Fructosamine and diabetes as predictors of mortality among Hispanic and non-Hispanic white breast cancer survivors.

NPJ Breast Cancer 2019 7;5. Epub 2019 Jan 7.

2Department of Epidemiology and Population Health and the James Graham Brown Cancer Center, University of Louisville, Louisville, KY USA.

Epidemiologic studies have found that elevated insulin levels and chronic hyperglycemia among breast cancer (BC) survivors are associated with poor prognosis; few of these studies have included Hispanic women in whom diabetes is highly prevalent. We examined the associations between circulating fructosamine-a biomarker of hyperglycemia and blood glucose control, self-reported diabetes, and risk of BC-specific and all-cause mortality among Hispanic and non-Hispanic white (NHW) women diagnosed with invasive BC. A total of 399 BC survivors (96 Hispanic, 303 NHW) contributed baseline data and plasma samples. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using multivariable Cox proportional hazards regression models. After a median follow-up time of 13 years, a total of 134 deaths occurred, of which 56 deaths were from BC. Diabetes was associated with BC-specific (HR, 2.89; 95% CI 1.27-6.60) and all-cause (HR, 2.10; 95% CI 1.24-3.55) mortality. Associations were stronger among women with clinically high fructosamine levels (>285 µmol/L) (BC-specific: HR, 4.25; 95% CI 1.67-10.80; all-cause: HR, 2.32; 95% CI 1.30-4.14) compared to women with normal levels (≤285 µmol/L). In mediation analysis, fructosamine explained 47% of the association between diabetes and all-cause mortality and 41% of BC-specific mortality; the largest attenuation was among Hispanics for all-cause mortality (56%). Our results demonstrate that poor glycemic control explains a large extent of the relationship between diabetes and mortality among women with invasive BC, particularly among Hispanic women. The associations we observed for BC mortality should be confirmed in larger studies of ethnically diverse BC patients.
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http://dx.doi.org/10.1038/s41523-018-0099-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6323117PMC
January 2019

The Influence of Education and Apolipoprotein 4 on Mortality in Community-Dwelling Elderly Men and Women.

J Aging Res 2018 25;2018:6037058. Epub 2018 Mar 25.

Department of Epidemiology and Population Health, School of Public Health and Information Sciences, University of Louisville, 485 E. Gray St., Louisville, KY 40202, USA.

We investigated the risk of death in relation to the apolipoprotein 4 allele and evaluated how it interacts with education in 504 elderly adults (mean age 73 years, 65.3% women) who were enrolled in 1993 into the New Mexico Aging Process Study. During 9 years of follow-up, apolipoprotein 2 appeared to be associated with a lower risk for all-cause mortality (hazard ratio (HR) = 0.73, 95% confidence interval (CI): 0.30-1.71) compared to apolipoprotein 3 carriers in models adjusted for age, sociodemographic variables, medical conditions, adiposity, and lifestyle factors. The apolipoprotein 4 allele conferred almost a threefold elevated risk of mortality (HR = 2.76, CI: 1.42-5.37). An interaction between education and apolipoprotein e4 (=0.027) was observed with the HR of mortality among e4 carriers compared to noncarriers being 1.59 (0.64-3.96) for those with ≥college education; 6.66 (1.90-23.4) for those with some college or trade; and 14.1 (3.03-65.6) for participants with ≤high school education. No significant interaction was identified between apolipoprotein E genotype and cognitive function for mortality risk. These findings suggest that genetic (apolipoprotein 4) and environmental (education) factors act interactively to influences survival in the elderly with higher education attenuating the adverse effect of apolipoprotein 4 on mortality.
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http://dx.doi.org/10.1155/2018/6037058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5889858PMC
March 2018

Genetic variation in TNFα, PPARγ, and IRS-1 genes, and their association with breast-cancer survival in the HEAL cohort.

Breast Cancer Res Treat 2018 Apr 18;168(2):567-576. Epub 2017 Dec 18.

Epidemiology Program, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

Purpose: Tumor necrosis factor-α (TNF-α), peroxisome proliferator-activated receptor-γ (PPARγ), and insulin receptor substrate-1 (IRS-1) are associated with obesity, insulin resistance, and inflammation. Few data exist on associations between polymorphisms in these genes and mortality in breast cancer survivors.

Methods: We investigated associations between TNF-α G > A (rs1800629); PPARγ ProAla (rs1801282); and IRS-1 GlyArg (rs1801278) polymorphisms and anthropometric variables, circulating levels of previously measured biomarkers, and tumor characteristics in 553 women enrolled in the Health, Eating, Activity, and Lifestyle Study, a multiethnic, prospective cohort study of women diagnosed with stage I-IIIA breast cancer between 1995 and 1999 (median follow-up 14.7 years).  Using Cox proportional hazards models adjusted for possible confounders, we evaluated associations between these polymorphisms and mortality.

Results: Carriers of the PPARγ variant allele had statistically significantly lower rates of type 2 diabetes (P = 0.04), lower BMI (P = 0.01), and HOMA scores [P = 0.004; non-Hispanic White (NHWs) only]; carriers of the TNF-α variant A allele had higher serum glucose (P = 0.004, NHW only); and the IRS-1 variant was associated with higher leptin levels (P = 0.003, Hispanics only). There were no associations between any of the polymorphisms and tumor characteristics. Among 141 deaths, 62 were due to breast cancer. Carriers of the TNF-α-variant A allele had a decreased risk of breast-cancer-specific mortality [hazard ratio (HR) 0.30; 95% confidence interval (CI) 0.10-0.83] and all-cause mortality (HR 0.51; 95% CI 0.28-0.91).

Conclusions: Neither the PPARγ nor the IRS-1 polymorphism was associated with mortality outcome. The TNF-α G > A polymorphism was associated with reduced breast-cancer-specific and all-cause mortality.
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http://dx.doi.org/10.1007/s10549-017-4621-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5839976PMC
April 2018

Associations between ALDH1A1 polymorphisms, alcohol consumption, and mortality among Hispanic and non-Hispanic white women diagnosed with breast cancer: the Breast Cancer Health Disparities Study.

Breast Cancer Res Treat 2018 Apr 30;168(2):443-455. Epub 2017 Nov 30.

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Office E-6144, Baltimore, MD, USA.

Purpose: ALDH1A1, one of the main isotopes of aldehyde dehydrogenase-1 is involved in the differentiation and protection of normal hematopoietic stem cells and functions in alcohol sensitivity and dependence. We evaluated the associations between ALDH1A1 polymorphisms, alcohol consumption, and mortality among Hispanic and non-Hispanic white (NHW) breast cancer (BC) cases from the Breast Cancer Health Disparities Study.

Methods: Nine SNPs in ALDH1A1 were evaluated in 920 Hispanic and 1372 NHW women diagnosed with incident invasive BC. Adjusted Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Models were stratified by Native American (NA) ancestry and alcohol consumption.

Results: A total of 443 deaths occurred over a median follow-up time of 11 years. After adjusting all results for multiple comparisons, rs7027604 was significantly associated with all-cause mortality (HR = 1.40; 95% CI 1.13-1.73, P  = 0.018). The rs1424482 CC genotype (HR = 1.69; 95% CI 1.20-2.37, P  = 0.027) and the rs7027604 AA genotype (HR = 1.65; 95% CI 1.21-2.26, P  = 0.018) were positively associated with non-BC mortality. Among long-term light drinkers, rs1888202 was associated with decreased all-cause mortality (HR = 0.36; 95% CI 0.20-0.64), while associations were not significant among non-drinkers or moderate/heavy drinkers (P  = 0.218). The increased risk of all-cause mortality associated with rs63319 was limited to women with low NA ancestry (HR = 1.53; 95% CI 1.19-1.97).

Conclusions: Multiple SNPs in ALDH1A1 were associated with increased risk of mortality after BC. Future BC studies examining the relationship between ALDH1A1 and mortality should consider the modifying effects of alcohol consumption and NA ancestry.
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http://dx.doi.org/10.1007/s10549-017-4600-2DOI Listing
April 2018

Healthy lifestyle impact on breast cancer-specific and all-cause mortality.

Breast Cancer Res Treat 2018 01 31;167(1):171-181. Epub 2017 Aug 31.

Department of Epidemiology and Population Health, School of Public Health and Information Sciences, James Graham Brown Cancer Center, University of Louisville, 485 E. Gray St., Louisville, KY, 40202, USA.

Purpose: While several studies have evaluated the association of combined lifestyle factors on breast cancer-specific mortality, few have included Hispanic women. We constructed a "healthy behavior index" (HBI) and evaluated its associations with mortality in non-Hispanic White (NHW) and Hispanic women diagnosed with breast cancer from the southwestern U.S.

Methods: Diet and lifestyle questionnaires were analyzed for 837 women diagnosed with invasive breast cancer (1999-2004) in New Mexico as part of the 4-Corners Women's Health Study. An HBI score ranging from 0 to 12 was based on dietary pattern, physical activity, smoking, alcohol consumption, and body size and shape, with increasing scores representing less healthy characteristics. Hazard ratios for mortality over 14 years of follow-up were estimated for HBI quartiles using Cox proportional hazards models adjusting for education and stratified by ethnicity and stage at diagnosis.

Results: A significant increasing trend was observed across HBI quartiles among all women, NHW women, and those diagnosed with localized or regional/distant stage of disease for all-cause (AC) mortality (p-trend = 0.006, 0.002, 0.03, respectively). AC mortality was increased >2-fold for all women and NHW women in HBI Q4 versus Q1 (HR = 2.18, 2.65, respectively). The association was stronger in women with regional/distant than localized stage of disease (HR = 2.62, 1.94, respectively). Associations for Hispanics or breast cancer-specific mortality were not significant.

Conclusions: These findings indicate the associations between the HBI and AC mortality, which appear to differ by ethnicity and stage at diagnosis. Interventions for breast cancer survivors should address the combination of lifestyle factors on prognosis.
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http://dx.doi.org/10.1007/s10549-017-4467-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5830105PMC
January 2018

Pre-diagnostic breastfeeding, adiposity, and mortality among parous Hispanic and non-Hispanic white women with invasive breast cancer: the Breast Cancer Health Disparities Study.

Breast Cancer Res Treat 2017 01 11;161(2):321-331. Epub 2016 Nov 11.

Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA.

Background: U.S. Hispanic women have high rates of parity, breastfeeding, and obesity. It is unclear whether these reproductive factors are associated with breast cancer (BC) mortality. We examined the associations between breastfeeding, parity, adiposity and BC-specific and overall mortality in Hispanic and non-Hispanic white (NHW) BC cases.

Methods: The study population included 2921 parous women (1477 Hispanics, 1444 NHWs) from the Breast Cancer Health Disparities Study with invasive BC diagnosed between 1995 and 2004. Information on reproductive history and lifestyle factors was collected by in-person interview. Overall and stratified Cox proportional hazard regression models by ethnicity, parity, and body mass index (BMI) at age 30 years were used to calculate hazard ratios (HR) and 95% confidence intervals (CI).

Results: After a median follow-up time of 11.2 years, a total of 679 deaths occurred. Pre-diagnostic breastfeeding was associated with a 16% reduction in mortality (HR 0.84; 95% 0.72-0.99) irrespective of ethnicity. Parity significantly modified the association between breastfeeding duration and mortality (p interaction = 0.05), with longer breastfeeding duration associated with lower risk among women who had ≤2 births (p trend = 0.02). Breastfeeding duration was associated with reduced risk of both BC-specific and overall mortality among women with BMI <25 kg/m, while positive associations were observed among women with BMI ≥25 kg/m (p interactions <0.01).

Conclusion: Pre-diagnostic breastfeeding was inversely associated with risk of mortality after BC, particularly in women of low parity or normal BMI. These results provide another reason to encourage breastfeeding and weight management among young women.
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http://dx.doi.org/10.1007/s10549-016-4048-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5226868PMC
January 2017

Obesity, maternal smoking and SHBG in neonates.

Diabetol Metab Syndr 2016 26;8:47. Epub 2016 Jul 26.

Division of Endocrinology, Metabolism and Diabetes, University of Louisville, ACB-A3G11, 550 Jackson Street, Louisville, KY 40202 USA.

Background: Sex hormone binding globulin (SHBG), a glycoprotein produced by hepatocytes that transports testosterone and other steroids in plasma, is a marker for developing metabolic syndrome and T2DM. SHBG is present in umbilical cord blood where it may be epigenetically regulated. This study was conducted to investigate whether the fetal environment, based on maternal pre-pregnancy weight, pregnancy weight gain or smoking during pregnancy, influence SHBG in newborns.

Methods: Maternal and newborn characteristics and SHBG levels and other variables were measured in cord and day 2 heel-stick blood samples in 60 healthy full-term singleton babies (31 F, 29 M).

Results: SHBG levels varied nearly fivefold among male and female newborns and were unrelated to sex, neonatal adiposity, determined by the Ponderal index and skinfold thickness, nor TNF∝ in cord blood. There were also no statistically significant associations between pre-pregnancy weight or pregnancy weight gain and newborn SHBG levels. However, cord blood SHBG was higher and insulin levels were lower when mothers were smokers, but normalized by day 2.

Discussion: While SHBG levels are low in obese children and adults, and portend the development of metabolic syndrome and T2DM, our study of healthy babies born to normal women, found no connection between maternal obesity or newborn adiposity and SHBG levels in newborns. Insofar as women who smoked during pregnancy were thinner and had lower cord blood insulin levels than nonsmokers, higher SHBG in their newborns at birth might have been due to insulin sensitivity, or perhaps to an effect of smoking on placental gene expression.

Conclusions: Factors other than maternal weight and pregnancy weight gain appear to be the major determinants of SHBG in newborns. Higher SHBG levels when mothers smoke during pregnancy may contribute to overweight beginning later in childhood. Whether newborn SHBG levels predict the development of overweight and metabolic syndrome remains to be determined.
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http://dx.doi.org/10.1186/s13098-016-0158-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4960749PMC
July 2016

Ethnic differences in the relationships between diabetes, early age adiposity and mortality among breast cancer survivors: the Breast Cancer Health Disparities Study.

Breast Cancer Res Treat 2016 05 26;157(1):167-78. Epub 2016 Apr 26.

Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA.

The contribution of type 2 diabetes and obesity on mortality in breast cancer (BC) patients has not been well studied among Hispanic women, in whom these exposures are highly prevalent. In a multi-center population-based study, we examined the associations between diabetes, multiple obesity measures, and mortality in 1180 Hispanic and 1298 non-Hispanic white (NHW) women who were diagnosed with incident invasive BC from the San Francisco Bay Area, New Mexico, Utah, Colorado, and Arizona. Adjusted hazard ratios (HR) and 95 % confidence intervals (CI) were calculated using Cox proportional hazards regression models. The median follow-up time from BC diagnosis to death was 10.8 years. In ethnic-stratified results, the association for BC-specific mortality among Hispanics was significantly increased (HR 1.85 95 % CI 1.11, 3.09), but the ethnic interaction was not statistically significant. In contrast, obesity at age 30 increased BC-specific mortality risk in NHW women (HR 2.33 95 % CI 1.36, 3.97) but not Hispanics (p-interaction = 0.045). Although there were no ethnic differences for all-cause mortality, diabetes, obesity at age 30, and post-diagnostic waist-hip ratio were significantly associated with all-cause mortality in all women. This study provides evidence that diabetes and adiposity, both modifiable, are prognostic factors among Hispanic and NHW BC patients.
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http://dx.doi.org/10.1007/s10549-016-3810-3DOI Listing
May 2016

Associations between prior HPV4 vaccine doses and cervical cancer screening participation.

Cancer Epidemiol 2016 06 18;42:108-14. Epub 2016 Apr 18.

University of Louisville, School of Medicine, Departments of Community and Geriatric Medicine, Obstetrics & Gynecology, Louisville, KY, USA; University of Louisville, School of Public Health and Information Sciences, Departments of Epidemiology & Population Health and Health Promotion & Behavioral Health Sciences, Louisville, KY, USA; University of Louisville, School of Engineering, Department of Bioengineering, Louisville, KY, USA.

Background: Cervical cancer screening, regardless of HPV vaccination, is a cornerstone of cancer prevention. This study evaluated associations between prior HPV vaccine doses and initiation and continued participation of screening by age at vaccination.

Methods: Using electronic medical records for a safety net healthcare system (Truman Medical Center), women aged 14-26y vaccinated (n=1123) between 07/01/2006 and 10/1/2009 were randomly selected and matched on birth year and health campus to unvaccinated (n=1123) women. Frequency of screening was determined through 07/01/2013. Hazard ratios (HR) for screening were estimated using Cox proportional hazards regression.

Results: Screening rates were higher after vaccination: unvaccinated (53%), first (62%), second (59%) or third (61%) doses. Women who initiated screening were less likely to complete the vaccine series, regardless of age. Women receiving one dose were more likely than unvaccinated women to initiate screening (HR=2.98 95% Confidence Interval (CI):2.45-3.61) and were more likely to screen than those receiving two (1 vs. 2, HR=2.94 95% CI:2.09-4.14) or three doses (1 vs. 3, HR=3.15 95% CI:2.21-4.48). Compared to unvaccinated women, women <21y who completed 3-doses were 1.8-times more likely to screen at ≥21y, whereas vaccinated women ≥21y were more likely to screen regardless of number of doses (p<0.0001).

Conclusions: Women who were vaccinated were more likely to screen than unvaccinated women; screening rate was highest after and occurred closest to the first vaccine dose. Research evaluating the efficacy of a one-dose vaccine is warranted and may provide both higher vaccination and screening rates.
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http://dx.doi.org/10.1016/j.canep.2016.04.003DOI Listing
June 2016

Associations of sex steroid hormones with mortality in women with breast cancer.

Breast Cancer Res Treat 2016 Feb 10;155(3):559-67. Epub 2016 Feb 10.

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

Epidemiological studies have demonstrated associations between circulating levels of sex steroid hormones and risk of breast cancer in postmenopausal women. However, data on associations with breast cancer survival are limited. We measured levels of estradiol, estrone, testosterone, and sex hormone-binding globulin (SHBG), in serum collected on average 30 months after diagnosis from 358 postmenopausal women diagnosed with stage I-IIIA breast cancer between 1995 and 1998 who participated in a multiethnic, prospective cohort study. Women were followed through December, 2012. We evaluated associations between log-transformed analytes and breast cancer-specific and all-cause mortality fitting multivariable Cox proportional hazards models. Over a median of 14.5 years of follow-up, 102 deaths occurred; 43 of these were due to breast cancer. In models adjusted for ethnicity/study site, age, body mass index, and tumor stage, increased levels of log-transformed SHBG were associated with reduced risk of both breast cancer-specific mortality (hazard ratio, HR 0.48; 95 % confidence interval, CI 0.26-0.89) and all-cause mortality (HR 0.64, 95 % CI 0.43-0.97). There were no associations between levels of estradiol, estrone, or testosterone for either endpoint. In subgroup analyses, after correction for multiple testing, increased estrone was significantly associated with reduced risk for breast cancer-specific mortality among participants with ER-negative tumors (HR 0.16, 95 % CI 0.05-0.63) but not among participants with ER-positive tumors. Increased serum levels of SHBG were associated with decreased risk of breast cancer-specific and all-cause mortality in women with breast cancer. These results should be confirmed in larger breast cancer survivor cohorts.
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http://dx.doi.org/10.1007/s10549-016-3704-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5793898PMC
February 2016

Adherence to cervical cancer screening varies by human papillomavirus vaccination status in a high-risk population.

Prev Med Rep 2015 31;2:711-6. Epub 2015 Jul 31.

University of Louisville, School of Public Health and Information Sciences, Department of Epidemiology and Population Health, Louisville, KY, USA; University of Louisville, School of Medicine, Department of Family and Geriatric Medicine, Louisville, KY, USA; University of Louisville, School of Medicine, Department of Obstetrics and Gynecology, Louisville, KY, USA; University of Louisville, School of Public Health and Information Sciences, Department of Health Promotion and Behavioral Health Sciences, Louisville, KY, USA; University of Louisville, Speed School of Engineering, Department of Bioengineering, Louisville, KY, USA.

Cervical cancer screening has reduced the incidence of cervical cancer over the past 75 years. The primary aim of this study was to determine if women receiving Gardasil™ (HPV4 vaccine) participated in future cervical cancer screening at the same rate as that observed for unvaccinated women matched on birth year and health care campus. This is a retrospective cohort study of subjects selected from 27,786 females born from 1980 to 1992 who received health care in the Truman Medical Center safety net health system in Kansas City Missouri, USA. 1154 women 14-26 years old who received at least one dose of HPV4 vaccine between 2006 and 2009 were chosen at random from the vaccine records. 1154 randomly chosen unvaccinated women were age and health campus matched to the vaccinated women and all were followed until July 1, 2013. Women who were screened after 21 years and received three vaccine doses before 21 years, had the lowest screening rate of 24%. Their only predictive factor for screening, compared to the unvaccinated, was being closer to 21 years than 14 years at vaccination (aOR = 1.71 95% CI: 1.45, 2.00). Women vaccinated with three doses and screened at or after 21 years had the highest screening rate of 84% predicting a six-fold increase in screening participation over no vaccine received (aOR = 5.94 95% CI: 3.77, 9.35). Our results suggest that women who receive HPV4 vaccination closer to 21 years, not 14, are more likely to participate in cervical cancer screening in an underserved US population.
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http://dx.doi.org/10.1016/j.pmedr.2015.07.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4721469PMC
February 2016

Cigarette Smoking and Breast Cancer Risk in Hispanic and Non-Hispanic White Women: The Breast Cancer Health Disparities Study.

J Womens Health (Larchmt) 2016 Mar 18;25(3):299-310. Epub 2015 Dec 18.

8 Department of Internal Medicine, University of Utah , Salt Lake City, Utah.

Objective: Few epidemiological studies have included Hispanics with the evaluation of the effects of cigarette smoking and breast cancer. We examined the relationship between cigarette smoking, ethnicity, and breast cancer risk using data from the Breast Cancer Health Disparities Study (BCHDS).

Materials And Methods: The BCHDS is a consortium of three population-based case-control studies, including U.S. non-Hispanic whites (NHWs) (1,525 cases; 1,593 controls), U.S. Hispanics/Native Americans (1,265 cases; 1,495 controls), and Mexican women (990 cases; 1,049 controls). Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs).

Results: Breast cancer risk was elevated among Mexican former smokers (OR 1.43, 95% CI 1.04-1.96) and among those who smoked ≥ 31 years (OR 1.95, 95% CI 1.13-3.35), compared to never smokers. In addition, Mexican former smokers with a history of alcohol consumption had increased breast cancer risk (OR 2.30, 95% CI 1.01-5.21). Among NHW premenopausal women, breast cancer risk was increased for smoking ≥ 20 cigarettes per day (OR 1.61, 95% CI 1.07-2.41).

Conclusion: Our findings suggest the possibility of ethnic differences with the associations between cigarette smoking and breast cancer risk.
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http://dx.doi.org/10.1089/jwh.2015.5502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4790199PMC
March 2016

Obesity, ethnicity, and quality of life among breast cancer survivors and women without breast cancer: the long-term quality of life follow-up study.

Cancer Causes Control 2016 Jan 30;27(1):115-24. Epub 2015 Oct 30.

Department of Epidemiology and Population Health, James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA.

Purpose: The purpose of this study was to examine the relationship between obesity and quality of life (QOL) among Hispanic and non-Hispanic white breast cancer survivors and population-based controls from the 'Long-Term Quality of Life Study'--a 12- to 15-year follow-up study of breast cancer cases/survivors and controls from New Mexico (n = 451).

Methods: Using multiple linear regressions, obesity measures [body mass index (BMI) ≥ 30 kg/m(2)] at baseline and follow-up interview were modeled with composite scores for physical and mental health from the SF-36 Quality of Life Survey. Interaction between ethnicity and BMI and change in BMI were evaluated. All models were adjusted for age, ethnicity, Charlson Index, depression, fatigue, and physical activity.

Results: Baseline obesity (β = -6.58, p = 0.04) was significantly associated with decreased mental health among survivors, but not among controls. Obesity at baseline and follow-up were significantly associated with decreased physical health among survivors (baseline β = -10.51, p = 0.004; follow-up β = -7.16, p = 0.02) and controls (baseline β = -11.07, p < 0.001; follow-up β = -5.18, p = 0.04). No significant interactions between ethnicity and BMI were observed.

Conclusions: Our findings provide unique information about a diverse population of breast cancer survivors and controls and the impact of obesity on the mental and physical aspects of QOL.
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http://dx.doi.org/10.1007/s10552-015-0688-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4871242PMC
January 2016

Active and passive cigarette smoking and mortality among Hispanic and non-Hispanic white women diagnosed with invasive breast cancer.

Ann Epidemiol 2015 Nov 28;25(11):824-31. Epub 2015 Aug 28.

Department of Internal Medicine, University of Utah, Salt Lake City.

Purpose: Women who smoke at breast cancer diagnosis have higher risk of breast cancer-specific and all-cause mortality than nonsmokers; however, differences by ethnicity or prognostic factors and risk for noncancer mortality have not been evaluated.

Methods: We examined associations of active and passive smoke exposure with mortality among Hispanic (n = 1020) and non-Hispanic white (n = 1198) women with invasive breast cancer in the Breast Cancer Health Disparities Study (median follow-up of 10.6 years).

Results: Risk of breast cancer-specific (HR = 1.55, 95% CI = 1.11-2.16) and all-cause (HR = 1.68, 95% CI = 1.30-2.17) mortality was increased for current smokers, with similar results stratified by ethnicity. Ever smokers had an increased risk of noncancer mortality (HR = 1.68, 95% CI = 1.12-2.51). Associations were strongest for current smokers who smoked for 20 years or more were postmenopausal, overweight and/or obese, or reported moderate and/or high alcohol consumption; however, interactions were not significant. Breast cancer-specific mortality was increased two fold for moderate and/or high recent passive smoke exposure among never smokers (HR = 2.12, 95% CI = 1.24-3.63).

Conclusions: Findings support associations of active-smoking and passive-smoking diagnosis with risk of breast cancer-specific and all-cause mortality and ever smoking with noncancer mortality, regardless of ethnicity, and other factors. Smoking is a modifiable lifestyle factor and effective smoking cessation, and maintenance programs should be routinely recommended for women with breast cancer.
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http://dx.doi.org/10.1016/j.annepidem.2015.08.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4609618PMC
November 2015

Treatment-related risk factors for arm lymphedema among long-term breast cancer survivors.

J Cancer Surviv 2015 Sep 26;9(3):422-30. Epub 2015 Apr 26.

Department of Epidemiology and Population Health, University of Louisville, Louisville, KY, 40202, USA.

Introduction: Treatment-related factors may increase the risk for arm lymphedema, which may occur after surgery or even many years after initial treatment for breast cancer. The association between treatment-related risk factors and development of arm lymphedema was examined for women who participated in the long-term quality of life (LTQOL) study, a 12-15-year follow-up of a breast cancer case-control study of Hispanic and non-Hispanic white women.

Methods: Among 199 cases, 43 women (15 Hispanic, 28 non-Hispanic white) reported physician-diagnosed lymphedema during follow-up. Multivariable logistic regression analysis was used to calculate the odds ratios (OR) and 95% confidence intervals (CI) for the association of risk factors with lymphedema, adjusting for relevant covariates.

Results: Tamoxifen had a non-significant, positive association with lymphedema (OR = 2.07, 95% CI 0.94-4.55, p =0.07). There were no significant associations with type of surgery, radiation, or chemotherapy. Risk was increased specifically in overweight and obese women (body mass index (BMI) > =25 kg/m(2)) treated with tamoxifen (OR = 2.62, 95% CI 0.99-6.93, p = 0.05).

Conclusions: This study suggests that breast cancer survivors with a BMI >25 who report the use of tamoxifen therapy may be at increased risk for arm lymphedema.

Implications For Cancer Survivors: Larger case-control studies and clinical trials should investigate the long-term association of tamoxifen treatment with arm lymphedema especially in overweight and obese women. Lymphedema risk may be another indication to consider a weight reduction program in breast cancer survivors.
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http://dx.doi.org/10.1007/s11764-014-0416-9DOI Listing
September 2015

Cardiovascular disease among women with and without diabetes mellitus and bilateral oophorectomy.

Diabetes Res Clin Pract 2015 Jun 25;108(3):473-81. Epub 2015 Feb 25.

Department of Medicine, University of Louisville, Louisville, KY 40202, United States.

Aims: Women with type-2 diabetes (DM2) are at high risk of cardiovascular disease (CVD) which may be partly due to increased ovarian androgen production. Since the association of bilateral oophorectomy (BSO) with CVD remains controversial, we evaluated whether BSO is inversely associated with CVD among DM2.

Methods: Data were obtained from a national sample of 9599 postmenopausal women. Adjusted estimates and 95% confidence intervals (CIs) were calculated using logistic and Cox regression.

Results: At baseline 2426 women had type-2 diabetes, of whom 580 had BSO. DM2 had adverse CVD risk profiles compared to women without diabetes, as did women with BSO with or without diabetes compared to those with intact ovaries. In DM2, BSO was positively associated with prevalent CVD (odds ratio: 1.63, 95%CI: 1.16-2.30). However, the higher odds were limited to women who had BSO before age 45 years (OR: 2.11, CI: 1.45-3.08). During a mean follow-up of 12.7 years, BSO in DM2 was positively associated with CVD mortality (hazard ratio: 2.23, CI: 1.25-3.99). Among women with BSO, those with family members who had MI before age 50 had elevated odds of CVD (OR: 2.29, CI: 1.56-3.37) compared to those without such family history (OR: 0.90, CI: 0.67-1.20), Pinteraction=0.04.

Conclusions: The risk of CVD is increased not decreased with BSO in DM2. Further, we propose that the association of BSO and CVD in young women with diabetes may partly reflect genetic susceptibility to CVD rather than an effect of ovarian hormones.
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http://dx.doi.org/10.1016/j.diabres.2015.02.017DOI Listing
June 2015

Physical activity and survival among Hispanic and non-Hispanic white long-term breast cancer survivors and population-based controls.

J Cancer Surviv 2015 Dec 5;9(4):650-9. Epub 2015 Mar 5.

Department of Epidemiology and Population Health, School of Public Health and Information Sciences, James Graham Brown Cancer Center, University of Louisville, 485 E. Gray St., Louisville, 40202, KY, USA.

Purpose: We investigated the association of physical activity with survival for 601 Hispanic women and 682 non-Hispanic white women who participated in the population-based breast cancer case-control New Mexico Women's Health Study.

Methods: We identified 240 deaths among cases diagnosed with a first primary invasive breast cancer between 1992 and 1994, and 88 deaths among controls. Follow-up extended through 2012 for cases and 2008 for controls. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression.

Results: Higher levels of total physical activity were inversely associated with all-cause mortality among Hispanic cases (Quartile (Q)4: HR = 0.55, 95% CI 0.31-0.99). A non-significant trend was observed for recreational activity in Hispanic cases also (Q4: HR = 0.50, 95% CI 0.23-1.09, p for trend = 0.08). No significant associations were noted for non-Hispanic white cases or for controls.

Conclusions: The results suggest that increasing physical activity may be protective against mortality in Hispanic women with breast cancer, despite reporting lower levels of recreational activity than non-Hispanic white women or Hispanic controls.

Implications For Cancer Survivors: Public health programs in Hispanic communities should promote physical activity in women as a means of decreasing breast cancer risk and improving survival.
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http://dx.doi.org/10.1007/s11764-015-0441-3DOI Listing
December 2015

Cognitive decline and polypharmacy in an elderly population.

J Am Geriatr Soc 2015 Feb;63(2):397-9

Department of Epidemiology and Population Health, School of Public Health and Information Sciences, University of Louisville, Louisville, Kentucky.

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http://dx.doi.org/10.1111/jgs.13283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4353494PMC
February 2015

Risk of heart failure among postmenopausal women: a secondary analysis of the randomized trial of vitamin D plus calcium of the women's health initiative.

Circ Heart Fail 2015 Jan 14;8(1):49-56. Epub 2014 Nov 14.

From the Division of Pharmacoepidemiology and Pharmacoeconomics (M.M.D.) and Department of Medicine (J.E.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Epidemiology, School of Public Health and Information Sciences, University of Louisville, KY (M.M.D., C.A.H., K.C.T., R.N.B.); Department of Family Medicine, Brown University School of Medicine, Providence, RI (C.B.E.); Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, OH (E.Z.G.); Division of Cardiology, University of California, San Francisco (L.K.); Heart and Vascular Institute, George Washington University, Washington DC (L.W.M.); Division of Preventive Medicine, University of Alabama, Birmingham (J.M.S.); Department of Epidemiology, Fairbanks School of Public Health, Indiana University, Indianapolis (Y.S.); and Department of Medicine, University of Massachusetts Medical School, Worcester (W.L.).

Background: Vitamin D supplementation may be an inexpensive intervention to reduce heart failure (HF) incidence. However, there are insufficient data to support this hypothesis. This study evaluates whether vitamin D plus calcium (CaD) supplementation is associated with lower rates of HF in postmenopausal women and whether the effects differ between those at high versus low risk for HF.

Methods And Results: Analyses were restricted to 35 983 (of original 36 282) women aged 50 to 79 years old in the Women's Health Initiative randomized trial of CaD supplementation who were randomized 1:1 in a double-blinded fashion to receive 1000 mg/d of calcium plus 400 IU/d of vitamin D3 or placebo. Overall, 744 adjudicated incident HF cases (intervention, 363; control, 381) occurred during a median follow-up of 7.1 (interquartile range, 1.6) years. CaD supplementation, compared with placebo, was not associated with reduced HF risk in the overall population, hazard ratio, 0.95; P=0.46. However, CaD supplementation had differential effects (P interaction=0.005) in subgroups stratified by baseline risk status of HF defined by the presence (high risk=17 449) or absence (low risk=18 534) of pre-existing HF precursors including coronary heart diseases, diabetes mellitus, or hypertension: 37% (hazard ratio, 0.63 [95% confidence interval, 0.46-0.87]) lower risk of HF in the low-risk versus hazard ratio, 1.06; P=0.51, in the high-risk subgroups.

Conclusions: CaD supplementation did not significantly reduce HF incidence in the overall cohort, however, it was beneficial among postmenopausal women without major HF precursors while of little value in high-risk subgroups. Additional studies are warranted to confirm these findings and investigate the underlying mechanism.

Clinical Trial Registration Url: http://www.clinicaltrials.gov. Unique identifier: NCT00000611.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.114.001738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4303506PMC
January 2015

Associations between ALOX, COX, and CRP polymorphisms and breast cancer among Hispanic and non-Hispanic white women: The breast cancer health disparities study.

Mol Carcinog 2015 Dec 22;54(12):1541-53. Epub 2014 Oct 22.

Department of Internal Medicine, University of Utah, Salt Lake City, Utah.

Chronic inflammation is suggested to be associated with specific cancer sites, including breast cancer. Recent research has focused on the roles of genes involved in the leukotriene/lipoxygenase and prostaglandin/cyclooxygenase pathways in breast cancer etiology. We hypothesized that genes in ALOX/COX pathways and CRP polymorphisms would be associated with breast cancer risk and mortality in our sample of Hispanic/Native American (NA) (1430 cases, 1599 controls) and non-Hispanic white (NHW) (2093 cases, 2610 controls) women. A total of 104 Ancestral Informative Markers was used to distinguish European and NA ancestry. The adaptive rank truncated product (ARTP) method was used to determine the significance of associations for each gene and the inflammation pathway with breast cancer risk and by NA ancestry. Overall, the pathway was associated with breast cancer risk (PARTP = 0.01). Two-way interactions with NA ancestry (P(adj)  < 0.05) were observed for ALOX12 (rs2292350, rs2271316) and PTGS1 (rs10306194). We observed increases in breast cancer risk in stratified analyses by tertiles of polyunsaturated fat intake for ALOX12 polymorphisms; the largest increase in risk was among women in the highest tertile with ALOX12 rs9904779CC (Odds Ratio (OR), 1.49; 95% Confidence Interval (CI) 1.14-1.94, P(adj) = 0.01). In a sub-analysis stratified by NSAIDs use, two-way interactions with NSAIDs use were found for ALOX12 rs9904779 (P(adj)  = 0.02), rs434473 (P(adj ) = 0.02), and rs1126667 (P(adj)  =  0.01); ORs for ALOX12 polymorphisms ranged from 1.55 to 1.64 among regular users. Associations were not observed with breast cancer mortality. These findings could support advances in the discovery of new pathways related to inflammation for breast cancer treatment.
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http://dx.doi.org/10.1002/mc.22228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4406776PMC
December 2015

Associations between CYP19A1 polymorphisms, Native American ancestry, and breast cancer risk and mortality: the Breast Cancer Health Disparities Study.

Cancer Causes Control 2014 Nov 5;25(11):1461-71. Epub 2014 Aug 5.

Department of Epidemiology and Population Health, James Graham Brown Cancer Center, School of Public Health and Information Sciences, University of Louisville, 485 E. Gray St., Louisville, KY, 40202, USA,

The cytochrome p450 family 19 gene (CYP19A1) encodes for aromatase, which catalyzes the final step in estrogen biosynthesis and conversion of androgens to estrogens. Genetic variation in CYP19A1 is linked to higher circulating estrogen levels and increased aromatase expression. Using data from the Breast Cancer Health Disparities Study, a consortium of three population-based case-control studies in the United States (n = 3,030 non-Hispanic Whites; n = 2,893 Hispanic/Native Americans (H/NA) and Mexico (n = 1,810), we examined influence of 25 CYP19A1 tagging single-nucleotide polymorphisms (SNPs) on breast cancer risk and mortality, considering NA ancestry. Odds ratios (ORs) and 95 % confidence intervals (CIs) and hazard ratios estimated breast cancer risk and mortality. After multiple comparison adjustment, none of the SNPs were significantly associated with breast cancer risk or mortality. Two SNPs remained significantly associated with increased breast cancer risk in women of moderate to high NA ancestry (≥29 %): rs700518, ORGG 1.36, 95 % CI 1.11-1.67 and rs11856927, ORGG 1.35, 95 % CI 1.05-1.72. A significant interaction was observed for rs2470144 and menopausal status (p adj = 0.03); risk was increased in postmenopausal (ORAA 1.22, 95 % CI 1.05-1.14), but not premenopausal (ORAA 0.78, 95 % CI 0.64-0.95) women. The absence of an overall association with CYP19A1 and breast cancer risk is similar to previous literature. However, this analysis provides support that variation in CYP19A1 may influence breast cancer risk differently in women with moderate to high NA ancestry. Additional research is warranted to investigate the how variation in an estrogen-regulating gene contributes to racial/ethnic disparities in breast cancer.
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http://dx.doi.org/10.1007/s10552-014-0448-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4435673PMC
November 2014

Central adiposity after breast cancer diagnosis is related to mortality in the Health, Eating, Activity, and Lifestyle study.

Breast Cancer Res Treat 2014 Aug 24;146(3):647-55. Epub 2014 Jul 24.

Applied Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, Rockville, MD, USA,

We examined whether waist circumference (WC) and waist-to-hip ratio (WHR) after breast cancer diagnosis are associated with all-cause or breast cancer-specific mortality and explored potential biological pathways mediating these relationships. Our analysis included 621 women diagnosed with local or regional breast cancer who participated in the Health, Eating, Activity, and Lifestyle study. At 30 (±4) months postdiagnosis, trained staff measured participants' waist and hip circumferences and obtained fasting serum samples for biomarker assays for assays of insulin, glucose, C-peptide, insulin growth factor-1 and binding protein-3, C-reactive protein (CRP), and adiponectin. We estimated multivariate hazard ratios (HR) and 95 % confidence intervals (CI) for death over ~9.5 years of follow-up. After adjustment for measured body mass index, treatment, comorbidities, race/ethnicity, diet quality, and postdiagnosis physical activity, WC was positively associated with all-cause mortality (HRq4:q1: 2.99, 95 % CI 1.14, 7.86) but its positive association with breast cancer-specific mortality was not statistically significant (HRq4:q1: 2.69, 95 % CI 0.69, 12.01). WHR was positively associated with all-cause mortality (HRq4:q1: 2.10, 95 % CI 1.08, 4.05) and breast cancer-specific mortality (HRq4:q1: 4.02, 95 % CI 1.31, 12.31). After adjustment for homeostatic model assessment (HOMA) score and C-reactive protein, risk estimates were attenuated and not statistically significant. In this diverse breast cancer survivor cohort, postdiagnosis WC and WHR were associated with all-cause mortality. Insulin resistance and inflammation may mediate the effects of central adiposity on mortality among breast cancer patients.
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http://dx.doi.org/10.1007/s10549-014-3048-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996589PMC
August 2014

Better postdiagnosis diet quality is associated with less cancer-related fatigue in breast cancer survivors.

J Cancer Surviv 2014 Dec 8;8(4):680-7. Epub 2014 Jul 8.

Applied Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, 9609 Medical Center Drive, MSC 9762, Bethesda, MD, 20892-9762, USA,

Purpose: A comprehensive understanding of the role of modifiable health behaviors in effective management of cancer-related fatigue is needed. Among breast cancer survivors, we examined how postdiagnosis diet quality, independently and jointly with physical activity, is related to fatigue, and the potential mediating role of inflammation.

Methods: Seven hundred seventy women diagnosed with stage 0-IIIA breast cancer in the Health, Eating, Activity, and Lifestyle study completed food frequency and physical activity questionnaires 30 months postdiagnosis. We scored diet quality using the Healthy Eating Index 2010 (HEI-2010). Serum concentrations of C-reactive protein (CRP) were measured in fasting 30-ml blood samples. Multidimensional fatigue was measured 41 months postdiagnosis using the 22-item revised Piper Fatigue Scale. In multivariate linear models, we determined whether fatigue was associated HEI-2010 quartiles (Q1-Q4), and a variable jointly reflecting HEI quartiles and physical activity levels.

Results: Survivors with better-quality diets (Q4 vs. Q1) had lower total fatigue (4.1 vs. 4.8, p-contrast = 0.003) and subscale scores (behavioral severity 3.4 vs. 4.2, p-contrast = 0.003; affective meaning 3.9 vs. 4.8, p-contrast = 0.007; sensory 4.4 vs. 5.2, p-contrast = 0.003; cognitive 4.6 vs. 5.0, p-contrast = 0.046). Least squares estimates of fatigue were similar in models including CRP. Compared to survivors with poor-quality diets and no physical activity, survivors with better-quality diets and meeting physical activity recommendations had significantly lower behavioral severity (3.2 vs. 4.7, p-contrast = 0.002) and sensory (3.8 vs. 4.8. p-contrast = 0.006) fatigue scores.

Conclusion: In this large breast cancer survivor cohort, postdiagnosis diet quality was inversely and independently associated with fatigue.

Implications For Cancer Survivors: Future interventions designed to improve multiple energy balance behaviors can provide insight into their associations with fatigue.
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http://dx.doi.org/10.1007/s11764-014-0381-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6993811PMC
December 2014

Epidermal growth factor receptor (EGFR) polymorphisms and breast cancer among Hispanic and non-Hispanic white women: the Breast Cancer Health Disparities Study.

Int J Mol Epidemiol Genet 2013 28;4(4):235-49. Epub 2013 Nov 28.

Department of Epidemiology & Population Health, School of Public Health and Information Sciences, University of Louisville Louisville, KY, USA.

The epidermal growth factor receptor (EGFR), a member of the ErbB family of receptor tyrosine kinases, functions in cellular processes essential to the development of cancer. Overexpression of EGFR in primary breast tumors has been linked with poor prognosis. We investigated the associations between 34 EGFR tagging SNPs and breast cancer risk and breast cancer-specific mortality in 4,703 Hispanic and 3,030 non-Hispanic white women from the Breast Cancer Health Disparities Study. We evaluated associations with risk of breast cancer defined by estrogen/progesterone receptor (ER/PR) tumor phenotype. Only one association remained statistically significant after adjusting for multiple comparisons. Rs2075112GA/AA was associated with reduced risk for ER-/PR+ tumor phenotype (odds ratio (OR), 0.34; 95% confidence interval (CI) 0.18-0.63, p adj=0.01). All additional results were significant prior to adjustment for multiple comparisons. Two of the EGFR polymorphisms were associated with breast cancer risk in the overall study population (rs11770531TT: OR, 0.56, 95% CI 0.37-0.84; and rs2293348AA: OR, 1.20, 95% CI 1.04-1.38) and two polymorphisms were associated with risk among Hispanics: rs6954351AA: OR, 2.50, 95% CI 1.32-4.76; and rs845558GA/AA: OR, 1.15, 95% CI 1.01-1.30. With regard to breast cancer-specific mortality, we found positive associations with rs6978771TT hazard ratio (HR), 1.68; 95% CI 1.11-2.56; rs9642391CC HR, 1.64; 95% CI 1.04-2.58; rs4947979AG/GG HR, 1.36; 95% CI 1.03-1.79; and rs845552GG HR, 1.62; 95% CI 1.05-2.49. Our findings provide additional insight for the role of EGFR in breast cancer development and prognosis. Further research is needed to elucidate EGFR's contribution to ethnic disparities in breast cancer.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3852643PMC
December 2013

Disentangling the body weight-bone mineral density association among breast cancer survivors: an examination of the independent roles of lean mass and fat mass.

BMC Cancer 2013 Oct 25;13:497. Epub 2013 Oct 25.

Applied Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, MD 20892, USA.

Background: Bone mineral density (BMD) and lean mass (LM) may both decrease in breast cancer survivors, thereby increasing risk of falls and fractures. Research is needed to determine whether lean mass (LM) and fat mass (FM) independently relate to BMD in this patient group.

Methods: The Health, Eating, Activity, and Lifestyle Study participants included 599 women, ages 29-87 years, diagnosed from 1995-1999 with stage 0-IIIA breast cancer, who underwent dual-energy X-ray absorptiometry scans approximately 6-months postdiagnosis. We calculated adjusted geometric means of total body BMD within quartiles (Q) of LM and FM. We also stratified LM-BMD associations by a fat mass index threshold that tracks with obesity (lower body fat: ≤ 12.9 kg/m2; higher body fat: >12.9 kg/m2) and stratified FM-BMD associations by appendicular lean mass index level corresponding with sarcopenia (non-sarcopenic: ≥ 5.45 kg/m2 and sarcopenic: < 5.45 kg/m2).

Results: Higher LM (Q4 vs. Q1) was associated with higher total body BMD overall (1.12 g/cm2 vs. 1.07 g/cm2, p-trend  < 0.0001), and among survivors with lower body fat (1.13 g/cm2 vs. 1.07 g/cm2, p-trend < 0.0001) and higher body fat (1.15 g/cm2 vs. 1.08 g/cm2, p-trend = 0.004). Higher FM (Q4 vs. Q1) was associated with higher total body BMD overall (1.12 g/cm2 vs. 1.07 g/cm2, p-trend < 0.0001) and among non-sarcopenic survivors (1.15 g/cm2 vs. 1.08 g/cm2, p < 0.0001), but the association was not significant among sarcopenic survivors (1.09 g/cm2 vs. 1.04 g/cm2, p-trend = 0.18).

Conclusion: Among breast cancer survivors, higher LM and FM were independently related to higher total body BMD. Future exercise interventions to prevent bone loss among survivors should consider the potential relevance of increasing and preserving LM.
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http://dx.doi.org/10.1186/1471-2407-13-497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3924343PMC
October 2013

Associations between null mutations in GSTT1 and GSTM1, the GSTP1 Ile(105)Val polymorphism, and mortality in breast cancer survivors.

Springerplus 2013 11;2:450. Epub 2013 Sep 11.

Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA USA.

Purpose: Here we assessed associations between null mutations in glutathione-S-transferase (GST)T1 and GSTM1 genes, and the rs1695 polymorphism in GSTP1 (Ile(105)Val), and risk of breast cancer-specific (n=45) and all-cause (n=99) mortality in a multiethnic, prospective cohort of 533 women diagnosed with stage I-IIIA breast cancer in 1995-1999, enrolled in the Health, Eating, Activity, and Lifestyle (HEAL) Study.

Methods: We measured the presence of the null mutation in GSTT1 and GSTM1, and the rs1695 polymorphism in GSTP1 by polymerase chain reaction. We assessed associations between breast-cancer specific and all-cause mortality using Cox proportional hazards models.

Results: Participants with ER-negative tumors were more likely to be GSTT1 null (χ(2)=4.52; P=0.03), and African American women were more likely to be GSTM1 null (χ(2)=34.36; P<0.0001). Neither GSTM1 nor GSTT1 null mutations were associated with breast cancer-specific or all-cause mortality. In a model adjusted for body mass index, race/ethnicity, tumor stage and treatment received at diagnosis, the variant Val allele of rs1695 was associated with increased risk of all-cause (HR=1.81, 95% CI 1.16-2.82, P=0.008), but not breast cancer-specific mortality. The GSTT1 null mutation was associated with significantly higher levels of C-reactive protein.

Conclusions: GSTM1 and GSTT1 null genotypes had no effect on outcome; however the variant allele of rs1695 appears to confer increased risk for all-cause mortality in breast-cancer survivors. Given the limited sample size of most studies examining associations between GST polymorphisms with breast cancer survival, and the lack of women undergoing more contemporary treatment protocols (treated prior to 1999), it may be helpful to re-examine this issue among larger samples of women diagnosed after the late 1990s, who all received some form of chemotherapy or radiotherapy.
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http://dx.doi.org/10.1186/2193-1801-2-450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3786079PMC
October 2013

Associations between genetic variants in the TGF-β signaling pathway and breast cancer risk among Hispanic and non-Hispanic white women.

Breast Cancer Res Treat 2013 Sep 14;141(2):287-97. Epub 2013 Sep 14.

Department of Epidemiology and Population Health, School of Public Health and Information Sciences, James Graham Brown Cancer Center, University of Louisville, 485 E. Gray St. Room, Louisville, KY, 40202, USA,

The TGF-β signaling pathway has a significant role in breast cancer initiation and promotion by regulating various cellular processes. We evaluated whether genetic variation in eight genes (TGF-β1, TGF-β2, TGF-βR1, TGF-βR2, TGF-βR3, RUNX1, RUNX2, and RUNX3) is associated with breast cancer risk in women from the Breast Cancer Health Disparities Study. A total of 3,524 cases (1,431 non-Hispanic whites (NHW); 2,093 Hispanics/Native Americans(NA)) and 4,209 population-based controls (1,599 NHWs; 2,610 Hispanics/NAs) were included in analyses. Genotypes for 47 single nucleotide polymorphisms (SNPs) were determined. Additionally, 104 ancestral informative markers estimated proportion of NA ancestry. Associations with breast cancer risk overall, by menopausal status, NA ancestry, and estrogen receptor (ER)/progesterone receptor tumor phenotype were evaluated. After adjustment for multiple comparisons, two SNPs were significantly associated with breast cancer risk: RUNX3 (rs906296 ORCG/GG = 1.15 95 % CI 1.04-1.26) and TGF-β1 (rs4803455 ORCA/AA = 0.89 95 % CI 0.81-0.98). RUNX3 (rs906296) and TGF-βR2 (rs3773644) were associated with risk in pre-menopausal women (p adj = 0.002 and 0.02, respectively) and in those with intermediate to high NA ancestry (p adj = 0.04 and 0.01, respectively). Self-reported race was strongly correlated with NA ancestry (r = 0.86). There was a significant interaction between NA ancestry and RUNX1 (rs7279383, p adj = 0.04). Four RUNX SNPs were associated with increased risk of ER- tumors. Results provide evidence that genetic variation in TGF-β and RUNX genes are associated with breast cancer risk. This is the first report of significant associations between genetic variants in TGF-β and RUNX genes and breast cancer risk among women of NA ancestry.
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http://dx.doi.org/10.1007/s10549-013-2690-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4088254PMC
September 2013