Background: Few studies have assessed the association of body size with postmenopausal breast can... more Background: Few studies have assessed the association of body size with postmenopausal breast cancer risk in Hispanic women. Findings are inconsistent and appear to contradict those reported for non-Hispanic white (NHW) women. Methods: We pooled interview and anthropometric data for 2,023 Hispanic and 2,384 NHW women from two U.S. population-based case-control studies. Using logistic regression analysis, we examined associations of overall and abdominal adiposity with risk of postmenopausal breast cancer defined by estrogen receptor (ER) and progesterone receptor (PR) status. Results: Weight gain was associated with increased risk of ER þ PR þ breast cancer in Hispanics not currently using menopausal hormone therapy (HT), but only among those with a low youngadult body mass index (BMI). In the subset of Hispanics with data on genetic ancestry, the association with weight gain was limited to women with lower Indigenous American ancestry. Young-adult BMI was inversely associated with both ER þ PR þ and ER À PR À breast cancers for both ethnicities combined, with similar, although nonsignificant, inverse trends in Hispanics and NHWs. Among all Hispanics, regardless of HT use, height was associated with risk of ER À PR À breast cancer and hip circumference with risk of breast cancer overall. Conclusions: Body size throughout adult life is associated with breast cancer risk among postmenopausal Hispanic women, as has been reported for NHW women. Associations were specific for breast cancer subtypes defined by hormone receptor status. Impact: Avoiding weight gain and maintaining a healthy weight are important strategies to reduce the risk of postmenopausal ER þ PR þ breast cancer, the most common breast cancer subtype.
Background: Few studies in Hispanic women have examined the relation between adult body size and ... more Background: Few studies in Hispanic women have examined the relation between adult body size and risk of premenopausal breast cancer defined by hormone receptor status. Methods: The Breast Cancer Health Disparities Study pooled interview and anthropometric data from two large U.S. population-based case-control studies. We examined associations of overall and abdominal adiposity with risk of estrogen receptor-and progesterone receptor-positive (ER þ PR þ ) and -negative (ER À PR À ) breast cancer in Hispanic and non-Hispanic White (NHW) women, calculating ORs and 95% confidence intervals. Results: Among Hispanics, risk of ER þ PR þ breast cancer was inversely associated with measures of overall adiposity, including young-adult and current body mass index (BMI). Risk was substantially reduced among those with high (above the median) young-adult BMI and current overweight or obesity. The findings for overall adiposity were similar for Hispanics and NHWs. In the subset of Hispanics with data on genetic ancestry, inverse associations of current BMI, and weight gain with ER þ PR þ breast cancer were limited to those with lower Indigenous American ancestry. For ER À PR À breast cancer, height was associated with increased risk, and young-adult BMI was associated with reduced risk. For all breast cancers combined, positive associations were seen for waist circumference, waist-to-hip ratio, and waist-to-height ratio in Hispanic women only. Conclusions: Our findings of body size associations with specific breast cancer subtypes among premenopausal Hispanic women were similar to those reported for NHW women. Impact: Adiposity throughout the premenopausal years has a major influence on breast cancer risk in Hispanic women. Cancer
Figure S2 shows differences in the prevalence of risk factors between controls from the younger b... more Figure S2 shows differences in the prevalence of risk factors between controls from the younger birth cohort when comparing foreign-born Asian American, U.S.-born Asian American, and U.S.-born non-Hispanic White women.
Cancer Epidemiology, Biomarkers & Prevention, Mar 8, 2023
Background: Breast cancer incidence rates in women of Asian descent have been increasing in the U... more Background: Breast cancer incidence rates in women of Asian descent have been increasing in the United States and Asia. Methods: In a case–control study of Asian American women from the San Francisco Bay Area, we assessed associations with birthplace and migration-related characteristics and compared risk factors between Asian American and non-Hispanic White women by birthplace and birth cohort. Results: Birthplace and migration-related characteristics were associated with breast cancer risk only among women in the younger birth cohort (1951–1984) that comprised 355 cases diagnosed at age ≤55 years and 276 sister and population controls. Breast cancer risk was marginally increased among foreign-born women [OR = 1.40; 95% confidence interval (CI), 0.97–2.03] and two-fold among foreign-born Chinese women (OR = 2.16; 95% CI, 1.21–3.88). Two-fold increased risks were associated with migration at age ≥40 years and longer U.S. residence (≥30 years or ≥75% of life). The education level was high among both cases and controls. Differences in the prevalence of risk factors by birthplace and birth cohort suggest temporal changes in reproductive and lifestyle-related factors. The prevalence in risk factors was similar between foreign-born and U.S.-born women in the younger birth cohort, and did not fully explain the observed associations with birthplace and other migration characteristics. Conclusions: In contrast to studies from earlier decades, younger foreign-born Asian American women had a higher risk of breast cancer than U.S.-born Asian American women. Impact: It is important and urgent to understand what factors drive the increasing burden of breast cancer in women of Asian descent and implement effective prevention programs.
Background: Data on breast-feeding and breast cancer risk are sparse and inconsistent for Hispani... more Background: Data on breast-feeding and breast cancer risk are sparse and inconsistent for Hispanic women. Methods: Pooling data for nearly 6,000 parous Hispanic women from four population-based studies conducted between 1995 and 2007 in the U.S. and Mexico, we examined the association of breast-feeding with risk of breast cancer overall and subtypes defined by estrogen receptor (ER) and progesterone receptor (PR) status, as well as the joint effects of breast-feeding, parity, and age
Bone morphogenetic proteins (BMP) are thoughtx to be important in breast cancer promotion and pro... more Bone morphogenetic proteins (BMP) are thoughtx to be important in breast cancer promotion and progression. We evaluated genetic variation in BMP-related genes and breast cancer risk among Hispanic (2111 cases, 2597 controls) and non-Hispanic white (NHW) (1481 cases, 1586 controls) women who participated in the 4-Corner's Breast Cancer Study, the Mexico Breast Cancer Study, and the San Francisco Bay Area Breast Cancer Study. BMP genes and their receptors evaluated include ACVR1, AVCR2A, ACVR2B, ACVRL1, BMP1, BMP2, BMP4, BMP6, BMP7, BMPR1A, BMPR1B, BMPR2, MSTN and GDF10. Additionally, 104 ancestral informative markers were assessed to discriminate between European and Native American ancestry. The importance of estrogen on BMP-related associations was suggested through unique associations by menopausal status and estrogen (ER) and progesterone (PR) receptor status of tumors. After adjustment for multiple comparisons ACVR1 (8 SNPs) was modestly associated with ER+PR+ tumors [odds ratios (ORs between 1.18 and 1.39 p adj < 0.05]. ACVR1 (3 SNPs) and BMP4 (3 SNPs) were associated with ER+PR-tumors (ORs 0.59 to 2.07 p adj < 0.05). BMPR2 was associated with ER-PR+ tumors (OR 4.20, 95% CI 1.62, 10.91 p adj < 0.05) as was GDF10 (2 SNPs ORs 3.62 and 3.85 p adj < 0.05). After adjustment for multiple comparisons several SNPs remained associated with ER-PR-tumors (p adj < 0.05) including ACVR1 BMP4, and GDF10 (ORs between 0.53 and 2.12). Differences in association also were observed by percentage of Native ancestry and menopausal status. Results support the hypothesis that genetic variation in BMPs is associated with breast cancer in this admixed population.
Table S2 shows differences in the prevalence of risk factors comparing foreign-born Asian America... more Table S2 shows differences in the prevalence of risk factors comparing foreign-born Asian American, U.S.-born Asian American, and U.S.-born non-Hispanic White controls
Table S3 shows differences in the prevalence of risk factors comparing foreign-born Asian America... more Table S3 shows differences in the prevalence of risk factors comparing foreign-born Asian American cases and foreign-born Asian American controls
Previously, we reported associations between breast cancer (BC) risk and tuna intake in non-Hispa... more Previously, we reported associations between breast cancer (BC) risk and tuna intake in non-Hispanic White (NHW) and Hispanic women, and processed meat intake among Hispanic women only. We also reported associations with SNPs in genes involved in the Convergence of Hormones, Inflammation, and Energy-related Factors (CHIEF) network. Given the multifactorial nature of BC etiology, we tested for interactions (GxE) between meat/fish intake and SNPs in selected CHIEF pathways using a set-based method that aggregates SNPs into groups for GxE association testing.The study population included Hispanic (1046 cases, 1331 controls) and NHW (1234 cases, 1468 controls) women from two US population-based case-control studies that are part of the Breast Cancer Health Disparities Study. Harmonized meat intake variables were dichotomized, and include red meat, processed meat, poultry, fish, and tuna. 734 SNPs were grouped into 107 genes based on loci. Genes were further grouped into 7 pathways based on biological function: CHIEF core, ALOX/COX, Interleukins, JAK/STAT/SOC, TLR/TNF, MAPK, and TGF-â. We performed the analysis in a top-down fashion, sequentially testing for interactions between meat/fish intake and pathways, genes within pathways, and SNPs within genes. To test pathways and genes, we used a set-based GxE approach that extends the adaptive rank truncated product (ARTP), and to test individual SNPs we used logistic regression. At gene and SNP level analyses, we applied Bonferroni corrections for the number of genes or SNPs tested. Analyses were stratified by ethnicity. Models were adjusted for study, age, education, menopausal status, family history of breast cancer, parity, body mass index, physical activity, education, intake of alcohol, fiber, calories, fat, carbohydrates, proteins, and genetic ancestry. We report results that showed statistically significant interactions at both pathway and gene levels. Analyses were conducted using the R programming language. Among NHW women, pathway-level analyses using ARTP identified an interaction between poultry intake and the interleukin/cytokine pathway, which was driven by the IL17A gene (2 SNPs); poultry intake was inversely associated with BC risk among carriers of the minor alleles in this gene. Among Hispanics, ARTP analyses identified an interaction between tuna intake and total fish intake and the Jak/Stat/SOC pathway, which was driven by STAT5A (tuna: 2 SNPs) and STAT5B (total fish and tuna: 3 SNPs). The positive associations between fish or tuna and BC risk were restricted to carriers of minor alleles in these two genes. Overall, our findings suggest a role for poultry and fish intake in chronic inflammation and tumor growth promotion in breast carcinogenesis and highlight specific genes that may play roles in these carcinogenic pathways. Citation Format: Andre E. Kim, Juan Pablo Lewinger, Shirong Zhang, Roger K. Wolff, Laura Fejerman, Esther M. John, Gabriela Torres-Mejia, Jennifer S. Herrick, Stephanie D. Boone, Avonne E. Connor, Lisa M. Hines, Kathy B. Baumgartner, Anna Giuliano, Martha L. Slattery, Mariana C. Stern. Interaction between meat and fish intake and genes involved in hormones, inflammation and energetic factors, and risk of breast cancer among Hispanic and Non-Hispanic White women: The Breast Cancer Health Disparities Study. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 799.
U.S. Hispanic women have, on average, 30% lower breast cancer incidence than non-Hispanic white (... more U.S. Hispanic women have, on average, 30% lower breast cancer incidence than non-Hispanic white (NHW) women. Genetic risk heterogeneity may contribute to this difference. Breast cancer genome-wide association studies (GWAS) conducted in women of European or Asian descent have identified multiple risk variants. In the present study we tested the association between 10 previously reported single nucleotide polymorphisms (SNPs) (rs13387042 in the 2q35 region, rs17157903-RELN gene, rs2067980-MRPS30, rs2180341-RNF146, rs2981582-FGFR2, rs3803662-TOX3, rs3817198-LSP1, rs7696175-TLR1, rs889312-MAP3k1 and rs999737-RAD51L1) and risk of breast cancer in a combined sample of 7774 women (2956 NHW women from the US and 4694 Hispanic women from the US and Mexico) who participated in one of three population-based case-control studies of breast cancer. Genetic ancestry was estimated with a set of 104 ancestry-informative markers (AIMs) selected to discriminate between Indigenous American and European ancestry. We used stratified logistic regression analyses to compare the associations with different genetic variants in NHWs and Hispanics classified by their proportion of Indigenous American (IA) ancestry (low, intermediate, high). Five of 10 SNPs were associated with breast cancer risk in this study. The associations with the FGFR2 and TOX3 variants were homogeneous across NHWs and Hispanics from all ancestry categories and the magnitude of the association in all women combined was similar to those previously reported. The other three variants were not associated with risk among NHWs, but in Hispanics statistically significant and heterogeneous associations were seen within the three categories of IA ancestry [2q35 per allele odds ratio (OR): 0.75 (95% CI = 0.50-1.15) for low IA ancestry, 1.19 (1.02-1.39) for intermediate IA ancestry, and 1.38 (1.04-1.82) for high IA ancestry, p interaction 0.02; RELN OR: 0.87 (0.59-1.29), 0.86 (0.72-1.04) and 1.69 (1.04-2.73), respectively, p interaction 0.03; TLR1 OR for risk allele homozygous: 0.74 (0.42-1.31), 1.39 (1.11-1.74) and 1.73 (1.19-2.52), respectively, p interaction 0.03]. Our results suggest that the degree of Indigenous American ancestry modifies the magnitude and direction of at least some of the previously reported variants associated with breast cancer risk. Genetic ancestry should be considered when assessing risk in women of mixed descent as well as for studies designed to discover causal mutations. This abstract is also presented as Poster A62. Citation Format: Laura Fejerman, Mariana C. Stern, Elad Ziv, Esther M. John, Gabriela Torres-Mejia, Lisa M. Hines, Roger Wolff, Wei Wang, Kathy Baumgartner, Anna Giuliano, Martha L. Slattery. Genetic susceptibility, genetic ancestry, and breast cancer risk among Hispanic and non-Hispanic white women. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr PR01.
Background:Breast cancer incidence rates in women of Asian descent have been increasing in the Un... more Background:Breast cancer incidence rates in women of Asian descent have been increasing in the United States and Asia.Methods:In a case–control study of Asian American women from the San Francisco Bay Area, we assessed associations with birthplace and migration-related characteristics and compared risk factors between Asian American and non-Hispanic White women by birthplace and birth cohort.Results:Birthplace and migration-related characteristics were associated with breast cancer risk only among women in the younger birth cohort (1951–1984) that comprised 355 cases diagnosed at age ≤55 years and 276 sister and population controls. Breast cancer risk was marginally increased among foreign-born women [OR = 1.40; 95% confidence interval (CI), 0.97–2.03] and two-fold among foreign-born Chinese women (OR = 2.16; 95% CI, 1.21–3.88). Two-fold increased risks were associated with migration at age ≥40 years and longer U.S. residence (≥30 years or ≥75% of life). The education level was high among both cases and controls. Differences in the prevalence of risk factors by birthplace and birth cohort suggest temporal changes in reproductive and lifestyle-related factors. The prevalence in risk factors was similar between foreign-born and U.S.-born women in the younger birth cohort, and did not fully explain the observed associations with birthplace and other migration characteristics.Conclusions:In contrast to studies from earlier decades, younger foreign-born Asian American women had a higher risk of breast cancer than U.S.-born Asian American women.Impact:It is important and urgent to understand what factors drive the increasing burden of breast cancer in women of Asian descent and implement effective prevention programs.
Table S5 shows differences in the prevalence of risk factors comparing foreign-born Asian America... more Table S5 shows differences in the prevalence of risk factors comparing foreign-born Asian American, U.S.-born Asian American, and U.S.-born non-Hispanic White women who were born from 1951-1984
supplemental Tables 1-5. Supplemental Table 1: Characteristics of Study Population. Supplemental ... more supplemental Tables 1-5. Supplemental Table 1: Characteristics of Study Population. Supplemental Table 2: Body Size Characteristics among Postmenopausal Controls, by Ethnicity and Genetic Admixture among Hispanics. Supplemental Table 3: Abdominal Adiposity Associations with Breast Cancer Risk in Hispanic Postmenopausal Women Measured &lt;12 Months after Diagnosis/Selection, by Use of Hormone Therapy. Supplemental Table 4: Abdominal Adiposity Associations with Breast Cancer Risk in NHW Postmenopausal Women Measured &lt;12 Months after Diagnosis/Selection, by Use of Hormone Therapy. Supplemental Table 5: Overall Adiposity Associations with ER+PR+ Breast Cancer in Postmenopausal Hispanic Women not Currently Using Hormone Therapy, by Genetic Ancestry.
Table S4 shows differences in the prevalence of risk factors comparing foreign-born Asian America... more Table S4 shows differences in the prevalence of risk factors comparing foreign-born Asian American cases and foreign-born Asian American controls aged 44-55 years
Figure S1 shows differences in the prevalence of risk factors between foreign-born and U.S.-born ... more Figure S1 shows differences in the prevalence of risk factors between foreign-born and U.S.-born Asian American cases from the younger birth cohort
Association between rs13387042 and rs7696175 and breast cancer risk, stratified by risk factor* a... more Association between rs13387042 and rs7696175 and breast cancer risk, stratified by risk factor* and Indigenous American (IA) genetic ancestry in Hispanic women from the Breast Cancer Health Disparities Study
Association between ten GWAS-identified SNPs and breast cancer risk, stratified by environmental ... more Association between ten GWAS-identified SNPs and breast cancer risk, stratified by environmental risk factors, in Hispanic women from the Breast Cancer Health Disparities Study
Association between rs13387042 (2q35) and estrogen receptor status-specific breast cancer risk, s... more Association between rs13387042 (2q35) and estrogen receptor status-specific breast cancer risk, stratified by Indigenous American genetic ancestry, hormone therapy use, and breastfeeding in Hispanic women from the Breast Cancer Health Disparities Study
The epidermal growth factor receptor (EGFR), a member of the ErbB family of receptor tyrosine kin... more 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. Rs2075112 GA/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 (rs11770531 TT :
Background: Few studies have assessed the association of body size with postmenopausal breast can... more Background: Few studies have assessed the association of body size with postmenopausal breast cancer risk in Hispanic women. Findings are inconsistent and appear to contradict those reported for non-Hispanic white (NHW) women. Methods: We pooled interview and anthropometric data for 2,023 Hispanic and 2,384 NHW women from two U.S. population-based case-control studies. Using logistic regression analysis, we examined associations of overall and abdominal adiposity with risk of postmenopausal breast cancer defined by estrogen receptor (ER) and progesterone receptor (PR) status. Results: Weight gain was associated with increased risk of ER þ PR þ breast cancer in Hispanics not currently using menopausal hormone therapy (HT), but only among those with a low youngadult body mass index (BMI). In the subset of Hispanics with data on genetic ancestry, the association with weight gain was limited to women with lower Indigenous American ancestry. Young-adult BMI was inversely associated with both ER þ PR þ and ER À PR À breast cancers for both ethnicities combined, with similar, although nonsignificant, inverse trends in Hispanics and NHWs. Among all Hispanics, regardless of HT use, height was associated with risk of ER À PR À breast cancer and hip circumference with risk of breast cancer overall. Conclusions: Body size throughout adult life is associated with breast cancer risk among postmenopausal Hispanic women, as has been reported for NHW women. Associations were specific for breast cancer subtypes defined by hormone receptor status. Impact: Avoiding weight gain and maintaining a healthy weight are important strategies to reduce the risk of postmenopausal ER þ PR þ breast cancer, the most common breast cancer subtype.
Background: Few studies in Hispanic women have examined the relation between adult body size and ... more Background: Few studies in Hispanic women have examined the relation between adult body size and risk of premenopausal breast cancer defined by hormone receptor status. Methods: The Breast Cancer Health Disparities Study pooled interview and anthropometric data from two large U.S. population-based case-control studies. We examined associations of overall and abdominal adiposity with risk of estrogen receptor-and progesterone receptor-positive (ER þ PR þ ) and -negative (ER À PR À ) breast cancer in Hispanic and non-Hispanic White (NHW) women, calculating ORs and 95% confidence intervals. Results: Among Hispanics, risk of ER þ PR þ breast cancer was inversely associated with measures of overall adiposity, including young-adult and current body mass index (BMI). Risk was substantially reduced among those with high (above the median) young-adult BMI and current overweight or obesity. The findings for overall adiposity were similar for Hispanics and NHWs. In the subset of Hispanics with data on genetic ancestry, inverse associations of current BMI, and weight gain with ER þ PR þ breast cancer were limited to those with lower Indigenous American ancestry. For ER À PR À breast cancer, height was associated with increased risk, and young-adult BMI was associated with reduced risk. For all breast cancers combined, positive associations were seen for waist circumference, waist-to-hip ratio, and waist-to-height ratio in Hispanic women only. Conclusions: Our findings of body size associations with specific breast cancer subtypes among premenopausal Hispanic women were similar to those reported for NHW women. Impact: Adiposity throughout the premenopausal years has a major influence on breast cancer risk in Hispanic women. Cancer
Figure S2 shows differences in the prevalence of risk factors between controls from the younger b... more Figure S2 shows differences in the prevalence of risk factors between controls from the younger birth cohort when comparing foreign-born Asian American, U.S.-born Asian American, and U.S.-born non-Hispanic White women.
Cancer Epidemiology, Biomarkers & Prevention, Mar 8, 2023
Background: Breast cancer incidence rates in women of Asian descent have been increasing in the U... more Background: Breast cancer incidence rates in women of Asian descent have been increasing in the United States and Asia. Methods: In a case–control study of Asian American women from the San Francisco Bay Area, we assessed associations with birthplace and migration-related characteristics and compared risk factors between Asian American and non-Hispanic White women by birthplace and birth cohort. Results: Birthplace and migration-related characteristics were associated with breast cancer risk only among women in the younger birth cohort (1951–1984) that comprised 355 cases diagnosed at age ≤55 years and 276 sister and population controls. Breast cancer risk was marginally increased among foreign-born women [OR = 1.40; 95% confidence interval (CI), 0.97–2.03] and two-fold among foreign-born Chinese women (OR = 2.16; 95% CI, 1.21–3.88). Two-fold increased risks were associated with migration at age ≥40 years and longer U.S. residence (≥30 years or ≥75% of life). The education level was high among both cases and controls. Differences in the prevalence of risk factors by birthplace and birth cohort suggest temporal changes in reproductive and lifestyle-related factors. The prevalence in risk factors was similar between foreign-born and U.S.-born women in the younger birth cohort, and did not fully explain the observed associations with birthplace and other migration characteristics. Conclusions: In contrast to studies from earlier decades, younger foreign-born Asian American women had a higher risk of breast cancer than U.S.-born Asian American women. Impact: It is important and urgent to understand what factors drive the increasing burden of breast cancer in women of Asian descent and implement effective prevention programs.
Background: Data on breast-feeding and breast cancer risk are sparse and inconsistent for Hispani... more Background: Data on breast-feeding and breast cancer risk are sparse and inconsistent for Hispanic women. Methods: Pooling data for nearly 6,000 parous Hispanic women from four population-based studies conducted between 1995 and 2007 in the U.S. and Mexico, we examined the association of breast-feeding with risk of breast cancer overall and subtypes defined by estrogen receptor (ER) and progesterone receptor (PR) status, as well as the joint effects of breast-feeding, parity, and age
Bone morphogenetic proteins (BMP) are thoughtx to be important in breast cancer promotion and pro... more Bone morphogenetic proteins (BMP) are thoughtx to be important in breast cancer promotion and progression. We evaluated genetic variation in BMP-related genes and breast cancer risk among Hispanic (2111 cases, 2597 controls) and non-Hispanic white (NHW) (1481 cases, 1586 controls) women who participated in the 4-Corner's Breast Cancer Study, the Mexico Breast Cancer Study, and the San Francisco Bay Area Breast Cancer Study. BMP genes and their receptors evaluated include ACVR1, AVCR2A, ACVR2B, ACVRL1, BMP1, BMP2, BMP4, BMP6, BMP7, BMPR1A, BMPR1B, BMPR2, MSTN and GDF10. Additionally, 104 ancestral informative markers were assessed to discriminate between European and Native American ancestry. The importance of estrogen on BMP-related associations was suggested through unique associations by menopausal status and estrogen (ER) and progesterone (PR) receptor status of tumors. After adjustment for multiple comparisons ACVR1 (8 SNPs) was modestly associated with ER+PR+ tumors [odds ratios (ORs between 1.18 and 1.39 p adj < 0.05]. ACVR1 (3 SNPs) and BMP4 (3 SNPs) were associated with ER+PR-tumors (ORs 0.59 to 2.07 p adj < 0.05). BMPR2 was associated with ER-PR+ tumors (OR 4.20, 95% CI 1.62, 10.91 p adj < 0.05) as was GDF10 (2 SNPs ORs 3.62 and 3.85 p adj < 0.05). After adjustment for multiple comparisons several SNPs remained associated with ER-PR-tumors (p adj < 0.05) including ACVR1 BMP4, and GDF10 (ORs between 0.53 and 2.12). Differences in association also were observed by percentage of Native ancestry and menopausal status. Results support the hypothesis that genetic variation in BMPs is associated with breast cancer in this admixed population.
Table S2 shows differences in the prevalence of risk factors comparing foreign-born Asian America... more Table S2 shows differences in the prevalence of risk factors comparing foreign-born Asian American, U.S.-born Asian American, and U.S.-born non-Hispanic White controls
Table S3 shows differences in the prevalence of risk factors comparing foreign-born Asian America... more Table S3 shows differences in the prevalence of risk factors comparing foreign-born Asian American cases and foreign-born Asian American controls
Previously, we reported associations between breast cancer (BC) risk and tuna intake in non-Hispa... more Previously, we reported associations between breast cancer (BC) risk and tuna intake in non-Hispanic White (NHW) and Hispanic women, and processed meat intake among Hispanic women only. We also reported associations with SNPs in genes involved in the Convergence of Hormones, Inflammation, and Energy-related Factors (CHIEF) network. Given the multifactorial nature of BC etiology, we tested for interactions (GxE) between meat/fish intake and SNPs in selected CHIEF pathways using a set-based method that aggregates SNPs into groups for GxE association testing.The study population included Hispanic (1046 cases, 1331 controls) and NHW (1234 cases, 1468 controls) women from two US population-based case-control studies that are part of the Breast Cancer Health Disparities Study. Harmonized meat intake variables were dichotomized, and include red meat, processed meat, poultry, fish, and tuna. 734 SNPs were grouped into 107 genes based on loci. Genes were further grouped into 7 pathways based on biological function: CHIEF core, ALOX/COX, Interleukins, JAK/STAT/SOC, TLR/TNF, MAPK, and TGF-â. We performed the analysis in a top-down fashion, sequentially testing for interactions between meat/fish intake and pathways, genes within pathways, and SNPs within genes. To test pathways and genes, we used a set-based GxE approach that extends the adaptive rank truncated product (ARTP), and to test individual SNPs we used logistic regression. At gene and SNP level analyses, we applied Bonferroni corrections for the number of genes or SNPs tested. Analyses were stratified by ethnicity. Models were adjusted for study, age, education, menopausal status, family history of breast cancer, parity, body mass index, physical activity, education, intake of alcohol, fiber, calories, fat, carbohydrates, proteins, and genetic ancestry. We report results that showed statistically significant interactions at both pathway and gene levels. Analyses were conducted using the R programming language. Among NHW women, pathway-level analyses using ARTP identified an interaction between poultry intake and the interleukin/cytokine pathway, which was driven by the IL17A gene (2 SNPs); poultry intake was inversely associated with BC risk among carriers of the minor alleles in this gene. Among Hispanics, ARTP analyses identified an interaction between tuna intake and total fish intake and the Jak/Stat/SOC pathway, which was driven by STAT5A (tuna: 2 SNPs) and STAT5B (total fish and tuna: 3 SNPs). The positive associations between fish or tuna and BC risk were restricted to carriers of minor alleles in these two genes. Overall, our findings suggest a role for poultry and fish intake in chronic inflammation and tumor growth promotion in breast carcinogenesis and highlight specific genes that may play roles in these carcinogenic pathways. Citation Format: Andre E. Kim, Juan Pablo Lewinger, Shirong Zhang, Roger K. Wolff, Laura Fejerman, Esther M. John, Gabriela Torres-Mejia, Jennifer S. Herrick, Stephanie D. Boone, Avonne E. Connor, Lisa M. Hines, Kathy B. Baumgartner, Anna Giuliano, Martha L. Slattery, Mariana C. Stern. Interaction between meat and fish intake and genes involved in hormones, inflammation and energetic factors, and risk of breast cancer among Hispanic and Non-Hispanic White women: The Breast Cancer Health Disparities Study. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 799.
U.S. Hispanic women have, on average, 30% lower breast cancer incidence than non-Hispanic white (... more U.S. Hispanic women have, on average, 30% lower breast cancer incidence than non-Hispanic white (NHW) women. Genetic risk heterogeneity may contribute to this difference. Breast cancer genome-wide association studies (GWAS) conducted in women of European or Asian descent have identified multiple risk variants. In the present study we tested the association between 10 previously reported single nucleotide polymorphisms (SNPs) (rs13387042 in the 2q35 region, rs17157903-RELN gene, rs2067980-MRPS30, rs2180341-RNF146, rs2981582-FGFR2, rs3803662-TOX3, rs3817198-LSP1, rs7696175-TLR1, rs889312-MAP3k1 and rs999737-RAD51L1) and risk of breast cancer in a combined sample of 7774 women (2956 NHW women from the US and 4694 Hispanic women from the US and Mexico) who participated in one of three population-based case-control studies of breast cancer. Genetic ancestry was estimated with a set of 104 ancestry-informative markers (AIMs) selected to discriminate between Indigenous American and European ancestry. We used stratified logistic regression analyses to compare the associations with different genetic variants in NHWs and Hispanics classified by their proportion of Indigenous American (IA) ancestry (low, intermediate, high). Five of 10 SNPs were associated with breast cancer risk in this study. The associations with the FGFR2 and TOX3 variants were homogeneous across NHWs and Hispanics from all ancestry categories and the magnitude of the association in all women combined was similar to those previously reported. The other three variants were not associated with risk among NHWs, but in Hispanics statistically significant and heterogeneous associations were seen within the three categories of IA ancestry [2q35 per allele odds ratio (OR): 0.75 (95% CI = 0.50-1.15) for low IA ancestry, 1.19 (1.02-1.39) for intermediate IA ancestry, and 1.38 (1.04-1.82) for high IA ancestry, p interaction 0.02; RELN OR: 0.87 (0.59-1.29), 0.86 (0.72-1.04) and 1.69 (1.04-2.73), respectively, p interaction 0.03; TLR1 OR for risk allele homozygous: 0.74 (0.42-1.31), 1.39 (1.11-1.74) and 1.73 (1.19-2.52), respectively, p interaction 0.03]. Our results suggest that the degree of Indigenous American ancestry modifies the magnitude and direction of at least some of the previously reported variants associated with breast cancer risk. Genetic ancestry should be considered when assessing risk in women of mixed descent as well as for studies designed to discover causal mutations. This abstract is also presented as Poster A62. Citation Format: Laura Fejerman, Mariana C. Stern, Elad Ziv, Esther M. John, Gabriela Torres-Mejia, Lisa M. Hines, Roger Wolff, Wei Wang, Kathy Baumgartner, Anna Giuliano, Martha L. Slattery. Genetic susceptibility, genetic ancestry, and breast cancer risk among Hispanic and non-Hispanic white women. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr PR01.
Background:Breast cancer incidence rates in women of Asian descent have been increasing in the Un... more Background:Breast cancer incidence rates in women of Asian descent have been increasing in the United States and Asia.Methods:In a case–control study of Asian American women from the San Francisco Bay Area, we assessed associations with birthplace and migration-related characteristics and compared risk factors between Asian American and non-Hispanic White women by birthplace and birth cohort.Results:Birthplace and migration-related characteristics were associated with breast cancer risk only among women in the younger birth cohort (1951–1984) that comprised 355 cases diagnosed at age ≤55 years and 276 sister and population controls. Breast cancer risk was marginally increased among foreign-born women [OR = 1.40; 95% confidence interval (CI), 0.97–2.03] and two-fold among foreign-born Chinese women (OR = 2.16; 95% CI, 1.21–3.88). Two-fold increased risks were associated with migration at age ≥40 years and longer U.S. residence (≥30 years or ≥75% of life). The education level was high among both cases and controls. Differences in the prevalence of risk factors by birthplace and birth cohort suggest temporal changes in reproductive and lifestyle-related factors. The prevalence in risk factors was similar between foreign-born and U.S.-born women in the younger birth cohort, and did not fully explain the observed associations with birthplace and other migration characteristics.Conclusions:In contrast to studies from earlier decades, younger foreign-born Asian American women had a higher risk of breast cancer than U.S.-born Asian American women.Impact:It is important and urgent to understand what factors drive the increasing burden of breast cancer in women of Asian descent and implement effective prevention programs.
Table S5 shows differences in the prevalence of risk factors comparing foreign-born Asian America... more Table S5 shows differences in the prevalence of risk factors comparing foreign-born Asian American, U.S.-born Asian American, and U.S.-born non-Hispanic White women who were born from 1951-1984
supplemental Tables 1-5. Supplemental Table 1: Characteristics of Study Population. Supplemental ... more supplemental Tables 1-5. Supplemental Table 1: Characteristics of Study Population. Supplemental Table 2: Body Size Characteristics among Postmenopausal Controls, by Ethnicity and Genetic Admixture among Hispanics. Supplemental Table 3: Abdominal Adiposity Associations with Breast Cancer Risk in Hispanic Postmenopausal Women Measured &lt;12 Months after Diagnosis/Selection, by Use of Hormone Therapy. Supplemental Table 4: Abdominal Adiposity Associations with Breast Cancer Risk in NHW Postmenopausal Women Measured &lt;12 Months after Diagnosis/Selection, by Use of Hormone Therapy. Supplemental Table 5: Overall Adiposity Associations with ER+PR+ Breast Cancer in Postmenopausal Hispanic Women not Currently Using Hormone Therapy, by Genetic Ancestry.
Table S4 shows differences in the prevalence of risk factors comparing foreign-born Asian America... more Table S4 shows differences in the prevalence of risk factors comparing foreign-born Asian American cases and foreign-born Asian American controls aged 44-55 years
Figure S1 shows differences in the prevalence of risk factors between foreign-born and U.S.-born ... more Figure S1 shows differences in the prevalence of risk factors between foreign-born and U.S.-born Asian American cases from the younger birth cohort
Association between rs13387042 and rs7696175 and breast cancer risk, stratified by risk factor* a... more Association between rs13387042 and rs7696175 and breast cancer risk, stratified by risk factor* and Indigenous American (IA) genetic ancestry in Hispanic women from the Breast Cancer Health Disparities Study
Association between ten GWAS-identified SNPs and breast cancer risk, stratified by environmental ... more Association between ten GWAS-identified SNPs and breast cancer risk, stratified by environmental risk factors, in Hispanic women from the Breast Cancer Health Disparities Study
Association between rs13387042 (2q35) and estrogen receptor status-specific breast cancer risk, s... more Association between rs13387042 (2q35) and estrogen receptor status-specific breast cancer risk, stratified by Indigenous American genetic ancestry, hormone therapy use, and breastfeeding in Hispanic women from the Breast Cancer Health Disparities Study
The epidermal growth factor receptor (EGFR), a member of the ErbB family of receptor tyrosine kin... more 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. Rs2075112 GA/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 (rs11770531 TT :
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