Publications by authors named "Stephanie D Boone"

16 Publications

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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

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

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

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

Red meat, poultry, and fish intake and breast cancer risk among Hispanic and Non-Hispanic white women: The Breast Cancer Health Disparities Study.

Cancer Causes Control 2016 Apr 22;27(4):527-43. Epub 2016 Feb 22.

Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine of USC, University of Southern California, 1441 Eastlake Avenue, Room 5421A, Los Angeles, CA, 90089, USA.

Purpose: There is suggestive but limited evidence for a relationship between meat intake and breast cancer (BC) risk. Few studies included Hispanic women. We investigated the association between meats and fish intake and BC risk among Hispanic and NHW women.

Methods: The study included NHW (1,982 cases and 2,218 controls) and the US Hispanics (1,777 cases and 2,218 controls) from two population-based case-control studies. Analyses considered menopausal status and percent Native American ancestry. We estimated pooled ORs combining harmonized data from both studies, and study- and race-/ethnicity-specific ORs that were combined using fixed or random effects models, depending on heterogeneity levels.

Results: When comparing highest versus lowest tertile of intake, among NHW we observed an association between tuna intake and BC risk (pooled OR 1.25; 95 % CI 1.05-1.50; trend p = 0.006). Among Hispanics, we observed an association between BC risk and processed meat intake (pooled OR 1.42; 95% CI 1.18-1.71; trend p < 0.001), and between white meat (OR 0.80; 95% CI 0.67-0.95; trend p = 0.01) and BC risk, driven by poultry. All these findings were supported by meta-analysis using fixed or random effect models and were restricted to estrogen receptor-positive tumors. Processed meats and poultry were not associated with BC risk among NHW women; red meat and fish were not associated with BC risk in either race/ethnic groups.

Conclusions: Our results suggest the presence of ethnic differences in associations between meat and BC risk that may contribute to BC disparities.
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http://dx.doi.org/10.1007/s10552-016-0727-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4821634PMC
April 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

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

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

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