Luis Enrique Gutierrez-Millan

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. Cancer Epidemiol Biomarkers Prev; 22(10); 1853–61. ©2013 AACR.

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.

The complete mitochondrial genomes of the yellowleg shrimp Farfantepenaeus californiensis and the blue shrimp Litopenaeus stylirostris (Crustacea: Decapoda).

Mitochondria play key roles in many cellular processes. Description of penaeid shrimp genes, including mitochondrial genomes are fairly recent and some are focusing on commercially important shrimp as the Pacific shrimp Litopenaeus vannamei that is being used for aquaculture not only in America, but also in Asia. Much less is known about other Pacific shrimp such as the yellowleg shrimp Farfantepenaeus californiensis and the blue shrimp Litopenaeus stylirostris. We report the complete mitogenomes from these last two Pacific shrimp species. Long DNA fragments were obtained by PCR and then used to get internal fragments for sequencing. The complete F. californiensis and L. stylirostris mtDNAs are 15,975 and 15,988 bp long, containing the 37 common sequences and a control region of 990 and 999 bp, respectively. The gene order is identical to that of the tiger shrimp Penaeus monodon. Secondary structures for the 22 tRNAs are proposed and phylogenetic relationships for selected complete crustacean mitogenomes are included. Phylogenomic relationships among five shrimp show strong statistical support for the monophyly of the genus across the analysis. Litopenaeus species define a clade, with close relationship to Farfantepenaeus, and both clade with the sister group of Penaeus and Fenneropenaeus.

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.

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.

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 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.

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.

Analysis of the Ictalurus pricei complex (Teleostei: Ictaluridae) in northwest Mexico based on mitochondrial DNA

Abstract The genus Ictalurus is represented in northwest Mexico by a taxonomically problematic group of populations informally treated as the Ictalurus pricei complex. Several morphological characters separate the undescribed catfish populations (Sinaloa catfish) in the Culiacan River and San Lorenzo River basins from the Yaqui catfish (Ictalurus pricei), the only catfish species described from the region. In this paper, a phylogenetic analysis of cytochrome oxidase subunit 1 supports the monophyly of the I. pricei complex (Yaqui and Sinaloa catfishes). The complex appears closely related to Ictalurus lupus, another species from the American Southwest.

Complete mitochondrial genome of Ictalurus pricei (Teleostei: Ictaluridae) and evidence of a cryptic Ictalurus species in Northwest Mexico.

Abstract The nominal Yaqui catfish, Ictalurus pricei, is a species of Ictaluridae (Siluriformes) often recorded from Northwest Mexico. Southern distribution members of the I. pricei complex in Northwest Mexico include at least one undescribed species that differs from Yaqui catfish in morphological features, herein called “Sinaloa Catfish”. Sequencing of four geographical mitogenome haplotypes of Yaqui catfish and Sinaloa catfish showed geographical haplotypes of I. pricei within a clade of specific identity, close to Sinaloa catfish haplotypes. Our molecular phylogeny represents a working hypothesis supporting information on the evolutionary relationships of the Ictalurus species from Western Mexico and Western USA.