Hypothesized role of pregnancy hormones on HER2+ breast tumor development.

Breast cancer incidence rates have declined among older but not younger women; the latter are more likely to be diagnosed with breast cancers carrying a poor prognosis. Epidemiological evidence supports an increase in breast cancer incidence following pregnancy with risk elevated as much as 10 years post-partum. We investigated the association between years since last full-term pregnancy at the time of diagnosis (≤10 or >10 years) and breast tumor subtype in a case series of premenopausal Hispanic women (n = 627). Participants were recruited in the United States, Mexico, and Spain. Cases with known estrogen receptor (ER), progesterone receptor (PR), and HER2 status, with one or more full-term pregnancies ≥1 year prior to diagnosis were eligible for this analysis. Cases were classified into three tumor subtypes according to hormone receptor (HR+ = ER+ and/or PR+; HR- = ER- and PR-) expression and HER2 status: HR+/HER2-, HER2+ (regardless of HR), and triple negative breast cancer. Case-only odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated for HER2+ tumors in reference to HR+/HER2- tumors. Participants were pooled in a mixed-effects logistic regression model with years since pregnancy as a fixed effect and study site as a random effect. When compared to HR+/HER2- cases, women with HER2+ tumors were more likely be diagnosed in the post-partum period of ≤10 years (OR = 1.68; 95 % CI, 1.12-2.52). The effect was present across all source populations and independent of the HR status of the HER2+ tumor. Adjusting for age at diagnosis (≤45 or >45 years) did not materially alter our results (OR = 1.78; 95 % CI, 1.08-2.93). These findings support the novel hypothesis that factors associated with the post-partum breast, possibly hormonal, are involved in the development of HER2+ tumors.

The carotenogenesis pathway via the isoprenoid-beta-carotene interference approach in a new strain of Dunaliella salina isolated from Baja California Mexico.

D. salina is one of the recognized natural sources to produce beta-carotene, and an useful model for studying the role of inhibitors and enhancers of carotenogenesis. However there is little information in D. salina regarding whether the isoprenoid substrate can be influenced by stress factors (carotenogenic) or selective inhibitors which in turn may further contribute to elucidate the early steps of carotenogenesis and biosynthesis of beta-carotene. In this study, Dunaliella salina (BC02) isolated from La Salina BC Mexico, was subjected to the method of isoprenoids-beta-carotene interference in order to promote the interruption or accumulation of the programmed biosynthesis of carotenoids. When Carotenogenic and non-carotenogenic cells of D. salina BC02 were grown under photoautotrophic growth conditions in the presence of 200 microM fosmidomycin, carotenogenesis and the synthesis of beta-carotene were interrupted after two days in cultured D. salina cells. This result is an indirect consequence of the inhibition of the synthesis of isoprenoids and activity of the recombinant DXR enzyme thereby preventing the conversion of 1-deoxy-D-xylulose 5-phosphate (DXP) to 2-C-methyl-D-erythritol (MEP) and consequently interrupts the early steps of carotenogenesis in D. salina. The effect at the level of proteins and RNA was not evident. Mevinolin treated D. salina cells exhibited carotenogenesis and beta-carotene levels very similar to those of control cell cultures indicating that mevinolin not pursued any indirect action in the biosynthesis of isoprenoids and had no effect at the level of the HMG-CoA reductase, the key enzyme of the Ac/MVA pathway.

Development and Psychometric Assessment of the Measure of Globalization Influence on Health Risk (MGIHR) Among Mexican Women with Breast Cancer.

Lacking in the literature are data addressing the extent to which changes in reproductive and lifestyle factors predispose women in developing nations to higher breast cancer rates, and the degree to which these are due to globalization influences. This article describes the development and psychometric assessment of an instrument intended to measure global, predominantly U.S., influences on breast cancer risk profile among women residing in Mexico. Using investigator consensus and a focus group methodology, the Measure of Globalization Influence on Health Risk (MGIHR) was developed and completed by 341 women. Psychometric analysis support the use of an 11-item Consumerism and Modernity scale and 7-item Reproductive Control and Gender Role scale. The MGIHR is a valid and reliable instrument for understanding changing lifestyle and reproductive factors for breast cancer risk and may provide a more complete understanding of breast cancer development and needed interventions.

Differentially expressed microRNAs in postpartum breast cancer in Hispanic women.

The risk of breast cancer transiently increases immediately following pregnancy; peaking between 3-7 years. The biology that underlies this risk window and the effect on the natural history of the disease is unknown. MicroRNAs (miRNAs) are small non-coding RNAs that have been shown to be dysregulated in breast cancer. We conducted miRNA profiling of 56 tumors from a case series of multiparous Hispanic women and assessed the pattern of expression by time since last full-term pregnancy. A data-driven splitting analysis on the pattern of 355 miRNAs separated the case series into two groups: a) an early group representing women diagnosed with breast cancer ≤ 5.2 years postpartum (n = 12), and b) a late group representing women diagnosed with breast cancer ≥ 5.3 years postpartum (n = 44). We identified 15 miRNAs with significant differential expression between the early and late postpartum groups; 60% of these miRNAs are encoded on the X chromosome. Ten miRNAs had a two-fold or higher difference in expression with miR-138, miR-660, miR-31, miR-135b, miR-17, miR-454, and miR-934 overexpressed in the early versus the late group; while miR-892a, miR-199a-5p, and miR-542-5p were underexpressed in the early versus the late postpartum group. The DNA methylation of three out of five tested miRNAs (miR-31, miR-135b, and miR-138) was lower in the early versus late postpartum group, and negatively correlated with miRNA expression. Here we show that miRNAs are differentially expressed and differentially methylated between tumors of the early versus late postpartum, suggesting that potential differences in epigenetic dysfunction may be operative in postpartum breast cancers.

Acculturation, Behavioral Factors, and Family History of Breast Cancer among Mexican and Mexican-American Women.

BACKGROUND: Incidence rates for breast cancer are higher among Mexican-American (MA) women in the United States than women living in Mexico. Studies have shown higher prevalence of breast cancer risk factors in more acculturated than less acculturated Hispanic/Latinas in the United States. We compared the prevalence of behavioral risk factors and family history of breast cancer by level of acculturation and country of residence in women of Mexican descent. METHODS: Data were collected from 1,201 newly diagnosed breast cancer patients living in Mexico (n = 581) and MAs in the United States (n = 620). MA participants were categorized into three acculturation groups (Spanish dominant, bilingual, and English dominant); women living in Mexico were used as the referent group. The prevalence of behavioral risk factors and family history of breast cancer were assessed according to acculturation level, adjusting for age at diagnosis and education. RESULTS: In the adjusted models, bilingual and English-dominant MAs were significantly more likely to have a body mass index of 30 kg/m(2) or greater, consume more than one alcoholic beverage a week, and report having a family history of breast cancer than women living in Mexico. All three U.S. acculturation groups were significantly more likely to have lower total energy expenditure (≤533 kcal/d) than women in Mexico. English-dominant women were significantly less likely to ever smoke cigarettes than the Mexican group. CONCLUSIONS: Our findings add to the limited scientific literature on the relationships among acculturation, health behavior, and family history of breast cancer in Mexican and MA women.

Sequence and conservation of a rRNA and tRNAVal mitochondrial gene fragment from Penaeus californiensis and comparison with Penaeus vannamei and Penaeus stylirostris.

Penaeus californiensis is an important species for shrimp fisheries in the Pacific Ocean and has recently been described as a potential cultured species, mainly through the winter season in subtropical regions. A fragment of the mitochondrial 12S rRNA-tRNAVal-16S rRNA genes from P. californiensis was sequenced and compared with the corresponding regions from Penaeus vannamei and Penaeus stylirostris. Purified mitochondrial DNA was used for polymerase chain reaction amplification with primers for 12S and 16S rRNA genes. A 1379 +/- 1-bp fragment was obtained, including 90% 16S rRNA, tRNAVal, and a portion of 12S rRNA, cloned, and sequenced. Genetic distances were calculated according to the Kimura 2-parameter distance model, and maximum-likelihood analysis was applied with 1000 bootstrap replications. Sequence identity of P. californiensis with both P. vannamei and P. stylirostris was 0.88, while for P. vannamei and P. stylirostris the identity was 0.92. Maximum-likelihood analysis grouped P. vannamei and P. stylirostris separately from P. californiensis.

Family history of breast and ovarian cancer and triple negative subtype in hispanic/latina women.

Familial breast and ovarian cancer prevalence was assessed among 1150 women of Mexican descent enrolled in a case-only, binational breast cancer study. Logistic regression was conducted to compare odds of triple negative breast cancer (TNBC) to non-TNBC according to family history of breast and breast or ovarian cancer among 914 of these women. Prevalence of breast cancer family history in a first- and first- or second-degree relative was 13.1% and 24.1%, respectively; that for breast or ovarian cancer in a first-degree relative was 14.9%. After adjustment for age and country of residence, women with a first-degree relative with breast cancer were more likely to be diagnosed with TNBC than non-TNBC (OR=1.98; 95% CI, 1.26-3.11). The odds of TNBC compared to non-TNBC were 1.93 (95% CI, 1.26-2.97) for women with a first-degree relative with breast or ovarian cancer. There were non-significant stronger associations between family history and TNBC among women diagnosed at age <50 compared to ≥50 years for breast cancer in a first-degree relative (P-interaction = 0.14) and a first- or second-degree relative (P-interaction = 0.07). Findings suggest that familial breast cancers are associated with triple negative subtype, possibly related to BRCA mutations in Hispanic/Latina women, which are strongly associated with TNBC. Family history is an important tool to identify Hispanic/Latina women who may be at increased risk of TNBC, and could benefit from prevention and early detection strategies.

Reproductive and hormonal risk profile according to language acculturation and country of residence in the Ella Binational Breast Cancer Study.

BACKGROUND: We compared the distribution of breast cancer reproductive and hormonal risk factors by level of acculturation and country of residence in women of Mexican descent. METHODS: To compare the distribution of breast cancer reproductive and hormonal risk factors by level of acculturation and country of residence in women of Mexican descent, taking into account level of education, we analyzed data on 581 Mexican and 620 Mexican American (MA) women with a history of invasive breast cancer from the Ella Binational Breast Cancer Study. An eight-item language-based acculturation measure was used to classify MA women. Multivariate logistic regression was used to test associations between language acculturation, country of residence, and reproductive and hormonal risk factors. RESULTS: After adjustment for age and education, compared to women residing in Mexico, English-dominant MAs were significantly more likely to have an earlier age at menarche (<12 years; odds ratio [OR]=2.08; 95% confidence interval [CI], 1.30-3.34), less likely to have a late age at first birth (≥30 years; OR=0.49; 95% CI, 0.25-0.97), and less likely to ever breastfeed (OR=0.13; 95% CI, 0.08-0.21). CONCLUSIONS: Differences in reproductive and hormonal risk profile according to language acculturation and country of residence are evident; some of these were explained by education. Results support continued efforts to educate Mexican and MA women on screening and early detection of breast cancer along with promotion of modifiable factors, such as breastfeeding.

Environmental arsenic exposure and serum matrix metalloproteinase-9.

The objective of this study was to evaluate the relationship between environmental arsenic exposure and serum matrix metalloproteinase (MMP)-9, a biomarker associated with cardiovascular disease and cancer. In a cross-sectional study of residents of Arizona, USA (n=215) and Sonora, Mexico (n=163), drinking water was assayed for total arsenic, and daily drinking water arsenic intake was estimated. Urine was speciated for arsenic, and concentrations were adjusted for specific gravity. Serum was analyzed for MMP-9 using ELISA. Mixed model linear regression was used to assess the relation among drinking water arsenic concentration, drinking water arsenic intake, urinary arsenic sum of species (the sum of arsenite, arsenate, monomethylarsonic acid and dimethylarsinic acid), and MMP-9, controlling for autocorrelation within households. Drinking water arsenic concentration and intake were positively associated with MMP-9, both in crude analysis and after adjustment for gender, country/ethnicity, age, body mass index, current smoking, and diabetes. Urinary arsenic sum of species was positively associated with MMP-9 in multivariable analysis only. Using Akaike's Information Criterion, arsenic concentration in drinking water provided a better fitting model of MMP-9 than either urinary arsenic or drinking water arsenic intake. In conclusion, arsenic exposure evaluated using all three exposure metrics was positively associated with MMP-9.

Reproductive factors, heterogeneity, and breast tumor subtypes in women of mexican descent.

BACKGROUND: Published data support the presence of etiologic heterogeneity by breast tumor subtype, but few studies have assessed this in Hispanic populations. METHODS: We assessed tumor subtype prevalence and associations between reproductive factors and tumor subtypes in 1,041 women of Mexican descent enrolled in a case-only, binational breast cancer study. Multinomial logistic regression comparing HER2(+) tumors and triple-negative breast cancer (TNBC) to luminal A tumors was conducted. RESULTS: Compared with women with luminal A tumors, those with a later age at first pregnancy were less likely to have TNBC [OR, 0.61; 95% confidence interval (CI), 0.39-0.95], whereas those with three or more full-term pregnancies were more likely to have TNBC (OR, 1.68; 95% CI, 1.10-2.55). A lower odds of TNBC was shown for longer menstruation duration, whether before first pregnancy (OR, 0.78; 95% CI, 0.65-0.93 per 10 years) or menopause (OR, 0.79; 95% CI, 0.69-0.91 per 10 years). Patients who reported breastfeeding for more than 12 months were over twice as likely to have TNBC than luminal A tumors (OR, 2.14; 95% CI, 1.24-3.68). Associations comparing HER2(+) with luminal A tumors were weak or nonexistent except for the interval between last full-term pregnancy and breast cancer diagnosis. CONCLUSIONS: Findings show etiologic heterogeneity by tumor subtype in a population of Hispanic women with unique reproductive profiles. IMPACT: Identification of etiologically distinct breast tumor subtypes can further improve our understanding of the disease and help provide personalized prevention and treatment regimens.

Association between parity and obesity in Mexican and Mexican-American women: findings from the Ella binational breast cancer study.

Obesity at diagnosis of breast cancer is associated with higher all-cause mortality and treatment-associated toxicities. We evaluated the association between parity and obesity in the Ella study, a population of Mexican and Mexican-American breast cancer patients with high parity. Obesity outcomes included body mass index (BMI) ≥30 kg/m(2), waist circumference (WC) ≥35 in (88 cm), and waist-to-hip-ratio (WHR) ≥0.85. Prevalence of obesity ([BMI] ≥ 30 kg/m(2)) was 38.9 %. For WC, the multivariate odds ratio (OR) (95 % confidence interval [CI]) for having WC ≥ 35 inches in women with ≥4 pregnancies relative to those with 1-2 pregnancies was 1.59 (1.01-2.47). Higher parity (≥4 pregnancies) was non-significantly associated with high BMI (OR = 1.10; 95 % CI 0.73-1.67). No positive association was observed for WHR. Our results suggest WC is independently associated with high parity in Hispanic women and may be an optimal target for post-partum weight loss interventions.

Binational arsenic exposure survey: methodology and estimated arsenic intake from drinking water and urinary arsenic concentrations.

The Binational Arsenic Exposure Survey (BAsES) was designed to evaluate probable arsenic exposures in selected areas of southern Arizona and northern Mexico, two regions with known elevated levels of arsenic in groundwater reserves. This paper describes the methodology of BAsES and the relationship between estimated arsenic intake from beverages and arsenic output in urine. Households from eight communities were selected for their varying groundwater arsenic concentrations in Arizona, USA and Sonora, Mexico. Adults responded to questionnaires and provided dietary information. A first morning urine void and water from all household drinking sources were collected. Associations between urinary arsenic concentration (total, organic, inorganic) and estimated level of arsenic consumed from water and other beverages were evaluated through crude associations and by random effects models. Median estimated total arsenic intake from beverages among participants from Arizona communities ranged from 1.7 to 14.1 µg/day compared to 0.6 to 3.4 µg/day among those from Mexico communities. In contrast, median urinary inorganic arsenic concentrations were greatest among participants from Hermosillo, Mexico (6.2 µg/L) whereas a high of 2.0 µg/L was found among participants from Ajo, Arizona. Estimated arsenic intake from drinking water was associated with urinary total arsenic concentration (p < 0.001), urinary inorganic arsenic concentration (p < 0.001), and urinary sum of species (p < 0.001). Urinary arsenic concentrations increased between 7% and 12% for each one percent increase in arsenic consumed from drinking water. Variability in arsenic intake from beverages and urinary arsenic output yielded counter intuitive results. Estimated intake of arsenic from all beverages was greatest among Arizonans yet participants in Mexico had higher urinary total and inorganic arsenic concentrations. Other contributors to urinary arsenic concentrations should be evaluated.