Pharmacological blockage of the CXCR4-CXCL12 axis in endometriosis leads to contrasting effects in proliferation, migration, and invasion.

High levels of inflammatory factors including chemokines have been reported in peritoneal fluid and blood of women with endometriosis. CXCL12 mediates its action by interaction with its specific receptor, CXCR4, reported to be elevated in human endometriosis lesions and in the rat model of endometriosis. Activation of the CXCR4-CXCL12 axis increases cell proliferation, migration, and invasion of cancer cells. To obtain insights into the CXCR4 expression profile in lesions and endometrium, as well as functionality of the CXCR4-CXCL12 axis in endometriosis, we analyzed the expression of CXCR4 in tissues on a human tissue array and studied CXCL12-mediated activation of proliferation, invasion, and migration in vitro. We observed differences in levels of nuclear CXCR4 expression among lesion types, being higher in ovarian lesions. Endometriotic cell lines (12Z) showed higher levels of CXCR4, proliferative and migratory potential, and AKT phosphorylation/kinase activity compared to untreated control cells (endometrial epithelial cells). CXCL12 and endometriotic stromal cell-enriched media increased proliferation of non-endometriotic epithelial cells. CXCL12 caused a significant increase in 12Z cell invasion but had no effect on migration; AMD3100, a CXCR4-specific inhibitor, significantly increased invasion of 12Z cells but decreased their migration. However, treatment with CXCL12 plus AMD3100 significantly decreased invasion and migration of 12Z cells. In conclusion, the CXCR4-CXCL12 axis is functional in endometriosis cells, but the expression of CXCR4 varies among lesions. CXCL12 promoted proliferation, migration, and invasion of endometriotic cells, while inducing AKT phosphorylation and activity, but pharmacologically blocking this axis in the absence of the ligand induced their invasiveness.

A Systematic Review of Measurement Properties of Patient-Reported Outcome Measures Used in Patients Undergoing Total Knee Arthroplasty.

BACKGROUND: While clinical research on total knee arthroplasty (TKA) outcomes is prevalent in the literature, studies often have poor methodological and reporting quality. A high-quality patient-reported outcome instrument is reliable, valid, and responsive. Many studies evaluate these properties, but none have done so with a systematic and accepted method. The objectives of this study were to identify patient-reported outcome measures (PROMs) for TKA, and to critically appraise, compare, and summarize their psychometric properties using accepted methods. METHODS: MEDLINE, EMBASE, SCOPUS, Web of Science, PsycINFO, and SPORTDiscus were systematically searched for articles with the following inclusion criteria: publication before December 2014, English language, non-generic PRO, and evaluation in the TKA population. Methodological quality and evidence of psychometric properties were assessed with the COnsensus-based standards for the selection of health Status Measurement INstruments (COSMIN) checklist and criteria for psychometric evidence proposed by the COSMIN group and Terwee et al. RESULTS: One-hundred fifteen studies on 32 PROMs were included in this review. Only the Work, Osteoarthritis or joint-Replacement Questionnaire, the Oxford Knee Score, and the Western Ontario and McMaster Universities Arthritis Index had 4 or more properties with positive evidence. CONCLUSION: Most TKA PROMs have limited evidence for their psychometric properties. Although not all the properties were studied, the Work, Osteoarthritis or joint-Replacement Questionnaire, with the highest overall ratings, could be a useful PROM for evaluating patients undergoing TKA. The methods and reporting of this literature can improve by following accepted guidelines.

The association of DNA Repair with breast cancer risk in women. A comparative observational study.

BACKGROUND: Previous studies have found a link between a low DNA repair capacity (DRC) level and increased cancer risk. Our aim was to assess the statistical association of DRC level and breast cancer (BC) using a case-control epidemiological study in a Hispanic community. METHODS: We conducted a comparative observational study to assess the validity of DRC in detecting BC in 824 women throughout Puerto Rico. Over a 6-year period, we compared 285 women newly diagnosed with BC to 539 without BC. DRC levels were measured in lymphocytes by means of a host-cell reactivation assay. We assessed the sensitivity, specificity, and association using the receiver operating characteristic curve analysis. Multiple logistic regression-adjusted odds ratios were estimated with 95% confidence level to measure the strength of the association of DRC and BC after adjusting for all confounders simultaneously. RESULTS: Compared to women without cancer, women with BC showed an average decrease of 60% in their DRC levels (p < 0.001). Validity of the association of DRC as a measure of BC risk showed a sensitivity of 83.2% and specificity of 77.6% (p < 0.0001). CONCLUSIONS: Our results support the usefulness of DRC level as a measure of BC risk. Additional studies in other populations are needed to further verify its usefulness.

Measurement Properties of Patient-Reported Outcome Measures Used in Patients Undergoing Total Hip Arthroplasty: A Systematic Review.

BACKGROUND: Many patient-reported outcome measures (PROMs) have been developed to evaluate patient conditions before and after total hip arthroplasty. Also, many studies have been conducted to evaluate and compare the qualities of these instruments. Previously published reports suggest that most of these studies have poor methodology. Recently, 2 sets of criteria were developed for guiding and assessing the methodological and psychometric quality of these PROMs. We reviewed PROMs for total hip arthroplasty patients and appraised the methodological quality and psychometric evidence of evaluations of each identified instrument. METHODS: Databases including PubMed, MEDLINE, Embase, CINAHL, the Cochrane Library, and others were searched for English-language articles published on or before April 14, 2017, using search terms related to outcome instrument, the condition or procedure of interest (hip arthroplasty), and psychometric properties. The methodological quality of the studies and the evidence of the psychometric properties were summarized and appraised using the COSMIN (COnsensus-based Standards for the selection of health Measurement INstruments) checklist and the psychometric evidence criteria. Overall psychometric ratings were derived by combining the 2 criteria. RESULTS: Seventy-three studies investigating 26 instruments were included. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Oxford Hip Score, Harris hip score, and the Hip disability and Osteoarthritis Outcome Score (HOOS) were the most frequently assessed instruments. The WOMAC had 5 properties with positive evidence and was the highest-quality instrument overall, followed by the HOOS and the European Health Interview Survey (EUROHIS)-Quality of Life 8-item index. CONCLUSIONS: Despite a large number of included studies, many had low COSMIN ratings. We recommend additional rigorous studies to explore the psychometric properties of these instruments. Furthermore, the development of a core outcome set for total hip arthroplasty clinical trials is needed.

Stress During Development of Experimental Endometriosis Influences Nerve Growth and Disease Progression.

PURPOSE: We have previously shown that stress prior to induction worsens clinical presentation and inflammatory parameters in a rat model of endometriosis. This study was designed to examine whether stress during the development of endometriosis can affect the growth of endometriotic implants through nerve growth and immune alterations. METHODS: Endometriosis was surgically induced in female Sprague-Dawley rats by suturing uterine horn implants onto the small intestine mesentery. Two weeks later, one group of rats (endo-stress) was subjected to a 10-day swim stress protocol. Controls had no stress (endo-no stress) or sutures only and stress (sham-stress). On day 60, all rats were killed and examined for the presence of endometriotic vesicles. The size of each vesicle was measured. The uterus and colon were removed and assessed for damage, cell infiltration, and expression of nerve growth factor (NGF), its receptors (p75 and Tropomyosin receptor kinase A (Trk-A)/pTrk-A), and calcitonin gene-related peptide, a sensory fiber marker. A differential analysis of peritoneal fluid white blood cell count was performed. RESULTS: Stress significantly increased endometriotic vesicle size but not colonic damage and increased infiltration of mast cells. Significantly increased expression of NGF and its receptors was found in the uterus of animals with endometriosis receiving stress. CONCLUSIONS: Stress stimulates the development of ectopic endometrial vesicles in an animal model of endometriosis and increases inflammatory cell recruitment to the peritoneum. In addition, stress promotes nerve fiber growth in the uterus.

Risk factors for atopic dermatitis in southern Puerto Rico.

BACKGROUND: Little is known about the risk factors and exposures to aeroallergens in subjects with atopic dermatitis (AD) in Southern Puerto Rico. The objective was to determine the prevalence of skin reactions to aeroallergens and to analyze self-reported risk factors in AD patients and a nonallergic control population. METHODS: A cross-sectional study was conducted which included 726 AD patients and 313 nonallergic control subjects. Skin tests were conducted and a questionnaire was self-applied to all participants. RESULTS: Seventy six percent of the AD patients showed at least one positive skin reactions to aeroallergens. Of these, half had positive skin reactions to dust mites, and one third to Periplaneta americana. A low prevalence of positive skin reactions to dog, cat, plant and fungal allergens was detected. Co-sensitivitity between mites and cockroaches was 30%. The maximum skin reactivity to mites was at 10-19 years of age declining thereafter while skin reactivity to dogs, and plants increased with age. No significant differences in the prevalence of skin reactions was observed between the male and female AD population. CONCLUSIONS. Of the aeroallergens tested, those derived from dust mites are the most frequent sensitizing agents in the AD patients. Data also showed that the mites B. tropicalis and E. maynei are also important sources of sensitization. Our study show that young patients specially those between the age of 10-19 age group are the most allergic. Being female, or having an asthmatic father are significant risk factors associated with allergen sensitivity in the AD population.

High blood pressure in school children: prevalence and risk factors.

BACKGROUND: The purpose of this study was to determine the prevalence of high blood pressure (HBP) and associated risk factors in school children 8 to 13 years of age. METHODS: Elementary school children (n = 1,066) were examined. Associations between HBP, body mass index (BMI), gender, ethnicity, and acanthosis nigricans (AN) were investigated using a school based cross-sectional study. Blood pressure was measured and the 95th percentile was used to determine HBP. Comparisons between children with and without HBP were utilized. The crude and multiple logistic regression adjusted odds ratios were used as measures of association. RESULTS: Females, Hispanics, overweight children, and children with AN had an increased likelihood of HBP. Overweight children (BMI > or = 85th percentile) and those with AN were at least twice as likely to present with HBP after controlling for confounding factors. CONCLUSION: Twenty one percent of school children had HBP, especially the prevalence was higher among the overweight and Hispanic group. The association identified here can be used as independent markers for increased likelihood of HBP in children.

Do acculturation and family cohesiveness influence severity of diabetes among Mexican Americans?

OBJECTIVE: The goal of the study was to evaluate the effect of family cohesiveness, acculturation, socioeconomic position, and cardiovascular risk factors on severity of diabetes among Mexican Americans. DESIGN AND STUDY POPULATION: The cross-sectional study involved a consecutive sample of 275 Mexican Americans under treatment for type 2 diabetes recruited from two medical clinics on the north side of Fort Worth, Texas. Recruitment and data collection took place during a span of 24 months from December 2001 to December 2003. MAIN OUTCOME MEASURES: Hemoglobin A1C levels, available from medical charts, were used to indicate diabetes severity. Cases were defined as individuals with poorly controlled or severe diabetes based upon abnormally high hemoglobin A1C (> or = 7.0). Controls were defined as individuals with well-controlled or mild-moderate diabetes as reflected in a normal hemoglobin A1C (< 7.0). A face-to-face questionnaire was administered to study participants to collect data on protective factors related to family cohesiveness and acculturation, demographic and socioeconomic variables, and cardiovascular risk factors. RESULTS: The results suggest that several variables were associated with severity of diabetes, including, receipt of food stamps, having spent childhood in Mexico, and current smoking status. Other variables representing acculturation and family cohesiveness, separately or combined, approached statistical significance. CONCLUSIONS: Even though acculturation and family cohesiveness as schemas were not statistically significant because of small sample size, they highlight the importance of building more sophisticated models for testing their association with severity of diabetes.

Alfa 1 antitrypsin and protease levels in Puerto Rican asthmatics: a pilot study.

A cross-sectional pilot study was conducted on a population of 119 asthmatics who had been recruited from the Emergency Room Department of a major hospital in Ponce, Puerto Rico. The purpose of the study was to determine the frequency of the MM, MS, and SS a-i-antiprotease variants. Also, we analyzed the serum levels of the alpha-1-antiprotease inhibitor, quantified the levels of serine proteases in homes of the asthmatic volunteers, and determined whether environmental levels of proteases, regardless of their sources, had any association with either asthma symptoms or alpha-1-antiprotease inhibitor phenotypes. Our results do not support the role of the alpha-1-antiprotease as a risk factor for asthma in the study population as previously reported. Patients who had visited the ED due to asthma on 3 or more occasions had significantly higher trypsin levels than those who had done so 2 or fewer times. Of those asthmatic patients who had daily symptoms, 40% had been exposed to high levels of elastase, and 33.3% to trypsin. Similarly, 52.9% of the patients with 2 or more hospitalizations a year had been exposed to high elastase levels, and 40.5% of asthma patients who had nocturnal asthma more than 3 times a week had been exposed to high levels of elastase.

Stress management affects outcomes in the pathophysiology of an endometriosis model.

We have previously shown detrimental effects of stress in an animal model of endometriosis. We now investigated whether the ability to control stress can affect disease parameters. Endometriosis was surgically induced in female Sprague-Dawley rats before exposing animals to a controllable (submerged platform) or uncontrollable (no platform) swim stress protocol. Corticosterone levels and fecal pellet numbers were measured as an indicator of stress. Uncontrollable stress increased the number and size of the endometriotic cysts. Rats receiving uncontrollable stress had higher anxiety than those exposed to controllable stress or no stress and higher corticosterone levels. Uncontrollable stressed rats had more colonic damage and uterine cell infiltration compared to no stress, while controllable stress rats showed less of an effect. Uncontrollable stress also increased both colonic and uterine motility. In summary, the level of stress controllability appears to modulate the behavior and pathophysiology of endometriosis and offers evidence for evaluating therapeutic interventions.

Characteristics of women with endometriosis from the USA and Puerto Rico.

PURPOSE: To describe lifetime differences in clinical characteristics of women with endometriosis between the USA and Puerto Rico. METHODS: A descriptive study using self-administered demographic and clinical questionnaires was undertaken. Women with self-reported surgically diagnosed endometriosis who completed questionnaires from the Endometriosis Association (EA), Wisconsin, USA (n = 4358) and the Endometriosis Research Program (ERP) in Puerto Rico (n = 878), were included in this study. We compared demographic, gynecological and clinical history, frequency of endometriosis-associated symptoms and co-morbidities. RESULTS: Although both groups have similar symptomatology, EA respondents had significantly higher rates of chronic pelvic pain and incapacitating pain than ERP participants. EA respondents were significantly more likely to report a history of problems getting pregnant, heavy bleeding, and hysterectomy than ERP respondents. Miscarriages were more frequently reported by the ERP group. Co-morbidities such as allergies, chronic fatigue syndrome, and fibromyalgia were more prevalent in EA respondents, whereas asthma was significantly more frequent in participants from ERP. CONCLUSIONS: Overall, women with endometriosis from the USA and Puerto Rico reported high rates of pain and infertility and a similar spectrum of symptoms. Those from the EA reported longer time to diagnosis, and diagnostic delays than those from the ERP, which may explain the observed increased in rates of endometriosis-related symptoms and co-morbidities in EA as compared to ERP.

Laparoscopic diagnosis and repair of asymptomatic bilateral inguinal hernias.

BACKGROUND: This study was designed to investigate age, sex, and side of hernia presentation at clinical examination as potential intrinsic risk factors for bilateral inguinal hernia (BIH), and to quantify the characteristics of clinical examination versus laparoscopy as a diagnostic tool for BIH. METHODS: A cross-sectional study was utilized to analyze 99 consecutive patients undergoing laparoscopic inguinal hernia repair. RESULTS: The incidence of BIH based on clinical examination alone was 49%, compared with 71% laparoscopically. Clinical examination of BIH resulted in 69% sensitivity, 100% specificity, 100% predictive value for bilateral diagnosis, and 57% predictive value for unilateral diagnosis. Left hernia presentation at clinical examination (prevalence rate ratio = 10.5, 95% confidence interval: 3.6 to 30.7) and male sex (prevalence rate ratio = 6.6, 95% confidence interval: 1.3 to 35.0) were found to be independent risk factors for BIH. CONCLUSIONS: Laparoscopy yields detection of BIH that would be missed by clinical examination alone. Furthermore, left-sided hernia and male sex were associated with BIH.

Using GIS technology to identify areas of tuberculosis transmission and incidence.

BACKGROUND: Currently in the U.S. it is recommended that tuberculosis screening and treatment programs be targeted at high-risk populations. While a strategy of targeted testing and treatment of persons most likely to develop tuberculosis is attractive, it is uncertain how best to accomplish this goal. In this study we seek to identify geographical areas where on-going tuberculosis transmission is occurring by linking Geographic Information Systems (GIS) technology with molecular surveillance. METHODS: This cross-sectional analysis was performed on data collected on persons newly diagnosed with culture positive tuberculosis at the Tarrant County Health Department (TCHD) between January 1, 1993 and December 31, 2000. Clinical isolates were molecularly characterized using IS6110-based RFLP analysis and spoligotyping methods to identify patients infected with the same strain. Residential addresses at the time of diagnosis of tuberculosis were geocoded and mapped according to strain characterization. Generalized estimating equations (GEE) analysis models were used to identify risk factors involved in clustering. RESULTS: Evaluation of the spatial distribution of cases within zip-code boundaries identified distinct areas of geographical distribution of same strain disease. We identified these geographical areas as having increased likelihood of on-going transmission. Based on this evidence we plan to perform geographically based screening and treatment programs. CONCLUSION: Using GIS analysis combined with molecular epidemiological surveillance may be an effective method for identifying instances of local transmission. These methods can be used to enhance targeted screening and control efforts, with the goal of interruption of disease transmission and ultimately incidence reduction.

Age, gender and seasonal patterns of asthma in emergency departments of southern Puerto Rico.

We report findings derived from 55,547 emergency department records of asthmatic patients in the city of Ponce, Puerto Rico over a period of six years. The analysis of the data revealed that mean age of the asthmatic cases were 18.7 +/- 17.8 years, with 45% percent of the patients in the 1-9 years age range, and proportionally decreasing with age. In children 1-9 years the percent of males was 1.5 times that of females, and in 10-19 year-old group, admissions to the emergency room for males and females was identical, and between 20-69 years of age, the female ratio ranged from 1.5-2.12. The data also demonstrated that there is a seasonal variation in the asthma attacks reaching its peak in December, and the lowest in June. In conclusion, in the city of Ponce, Puerto Rico, emergency department usage due to asthma attacks show a seasonal variation, and males are more affected by asthma at younger ages while females are more affected at older ages. These findings strongly suggest that emergency department usage due to asthma attacks is highly common and represents an important place where specialized health care delivery is needed. With the implementation of dedicated asthma centers, specialized health care delivery can be easily accomplished. In addition, our data supports the that asthma should be declared a public health problem and a reportable disease.

Prognostic factors of severe asthma in Puerto Rico.

Asthma in Puerto Rico is a serious Public Health Problem. This study extends our cross-sectional self-reported asthma prevalence survey of 3,000 volunteers. The purpose of the present study was to analyze the importance of known prognostic factors of asthma severity among 486 self-reported participants. Patients with more than one visit to the emergency room in the previous 12 months due to asthma exacerbations were classified as cases of "severe asthma", and those asthmatic patients who did not visit emergency rooms were classified as "non-severe asthmatic subjects". Severe cases and non-severe asthmatic subjects were compared regarding age, sex, family history of asthma, presence of household pets, and in the previous 12 months: history of hospitalization due to asthma, respiratory infections, tobacco smoking, exposure to passive smoking, and avoidance of passive smoking. Crude and logistic regression adjusted odds ratio was used as a measure of association between each prognostic factor, and the outcome namely severe asthma, while adjusting for all confounders simultaneously. The results clearly showed that previous hospitalizations due to asthma (OR = 7.3, p < 0.0001) and frequent of respiratory infection (OR = 2.5, p = 0.0003) were prognostic factors associated with increased asthma severity. A statistically significant, two percent less likelihood to have severe asthma for each year of age was found. Weak associations were found between asthma severity and male gender, family history of asthma, passive smoking, and presence of household pets. Avoidance of environmental tobacco exposure (passive smoking) was found to be an important and statistically significant protective factor associated with a 47% less likelihood for severe asthma. In conclusion, appropriate management of patients with history of hospitalization due to asthma is very important. The correct management of respiratory infection in asthmatic patients may result in a reduction of up to 60 percent of the odds of having asthma severe enough to require emergency treatment, and may reduced by 86.3 percent hospitalizations.

Differential promoter methylation of kinesin family member 1a in plasma is associated with breast cancer and DNA repair capacity.

Methylation alterations of CpG islands, CpG island shores and first exons are key events in the formation and progression of human cancer, and an increasing number of differentially methylated regions and genes have been identified in breast cancer. Recent studies of the breast cancer methylome using deep sequencing and microarray platforms are providing a novel insight on the different roles aberrant methylation plays in molecular subtypes of breast cancer. Accumulating evidence from a subset of studies suggests that promoter methylation of tumor-suppressor genes associated with breast cancer can be quantified in circulating DNA. However, there is a paucity of studies that examine the combined presence of genetic and epigenetic alterations associated with breast cancer using blood-based assays. Dysregulation of DNA repair capacity (DRC) is a genetic risk factor for breast cancer that has been measured in lymphocytes. We isolated plasma DNA from 340 participants in a breast cancer case control project to study promoter methylation levels of five genes previously shown to be associated with breast cancer in frozen tissue and in cell line DNA: MAL, KIF1A, FKBP4, VGF and OGDHL. Methylation of at least one gene was found in 49% of the cases compared to 20% of the controls. Three of the four genes had receiver characteristic operator curve values of ≥ 0.50: MAL (0.64), KIF1A (0.51) and OGDHL (0.53). KIF1A promoter methylation was associated with breast cancer and inversely associated with DRC. This is the first evidence of a significant association between genetic and epigenetic alterations in breast cancer using blood-based tests. The potential diagnostic utility of these biomarkers and their relevance for breast cancer risk prediction should be examined in larger cohorts.

Women with endometriosis have a higher DNA repair capacity and diminished breast cancer risk.

INTRODUCTION: Breast cancer (BC) and endometriosis are important reproductive health diseases for women. Although endometriosis is not a malignant condition, some of its characteristics mimic that of a malignancy. Endometriosis is associated with increased risk of certain cancers; however, whether it alters BC risk is unclear. This study evaluates the association of endometriosis and BC and explores whether DNA repair capacity (DRC) plays a role in such a relationship. MATERIALS AND METHODS: A case-control study of 991 women (385 with BC and 606 controls, all recruited over 5 years) was undertaken in Puerto Rico. Eighty participants with self-reported surgically diagnosed endometriosis were identified, 20 of whom also had a diagnosis of BC. Data from a structured questionnaire and DRC measurements were assessed to determine the association between BC, DRC, and endometriosis. RESULTS: Participants with BC cases were 50% less likely to have history of endometriosis (OR = 0.5 95%CI: 0.3, 0.9, p = 0.038) than women without BC controls. Findings that did not reach statistical significance included the following: women with history of endometriosis had a slightly higher DRC level than those without it; BC cases and history of endometriosis were less likely to have had endometriosis diagnosis before age 38 as compared to controls with endometriosis. DISCUSSION: Here we report an inverse association between endometriosis and BC, the former possibly conferring a protective effect on the latter. Although the mechanisms involved are unknown they may include protection provided by higher DRC and or hormonal treatments for endometriosis. A larger sample of endometriosis cases is necessary to confirm these results and answer the question of whether a higher DRC capacity may contribute to this potential protection, and to identify other factors at play.

Differential expression of DNA repair genes in Hispanic women with breast cancer.

Previous studies have found a link between a low DNA repair capacity (DRC) level and increased risk for breast cancer (BC). A recent study by Matta et al. 2012 showed that women with BC have an average reduction of 60% in DRC compared to controls (P < 0.001). Using the same group of Hispanic women, we selected a subgroup of cases (n=35) and controls (n=2) who donated their tumors and normal tissue for performing molecular studies in order to 1) compare the expression of DNA repair genes in breast tissue between BC cases and controls without this disease, 2) assess the correlation between gene expression and DRC levels, 3) examine whether DRC levels are associated with tumor DNA repair gene expression profiling when women were stratified according to their hormone receptor status. DRC levels were measured in lymphocytes by means of a host-cell reactivation assay. Gene expression levels were measured in tumors by means of DNA microarray analysis. Twenty-one DNA repair genes were found to be differentially and significantly expressed in women with BC. Those candidate genes were CHEK2, EME1 (MMS4L), ERCC3 (XPB), FANCM, H2AFX (H2AX), HMGB1, HUS1, MBD4, NEIL3, PCNA, RAD1, RAD23B, RAD51, RAD54B, RDM1 (RAD52B), SHFM1 (DSS1), TP1, UBE2N (UBC13) and XRCC5 (Ku80). Most DNA repair genes (n=18 or 82%) were overexpressed, ranging from 3.76-fold (RDM1) to 1.47-fold (XRCC5). Only 4 genes (18%) were underexpressed, ranging from 62% (SAPCD1) to 25% (RAD23B). Statistically significant positive correlations between DRC level and gene expression were found for the RAD51, FANCB and FANCA genes. We discuss the clinical and translational significance of these findings. Our results support the usefulness of studying DNA repair as a measure of BC risk. This study also provides a list of candidate DNA repair genes that might be associated with dysregulation of DNA repair in breast cancer.

Breast Cancer and DNA Repair Capacity: Association With Use of Multivitamin and Calcium Supplements.

CONTEXT: Breast cancer (BC) is the most common cancer in women, with over 1 million new cases diagnosed every year worldwide. Over recent decades, considerable interest has emerged regarding whether vitamins and/or other supplements can lower the risk of BC. However, previous epidemiologic studies that investigated the association between intake of multivitamin and supplements of single vitamins and minerals and BC risk have reported conflicting results. Whether vitamins can actually reduce BC risk is still controversial. OBJECTIVE: This study examined whether multivitamin and calcium use was associated with BC incidence and DNA repair capacity (DRC). DESIGN: The research team designed an observational, case-control study. SETTING: All work was performed at the Ponce School of Medicine and Health Sciences under the direct supervision of principal investigator Dr Jaime Matta. PARTICIPANTS: Participants were 836 women recruited primarily from the private practices of oncologists, gynecologists, and surgeons in Puerto Rico. INTERVENTIONS: A total of 312 individuals in the breast cancer (BC) group and 524 individuals in the control group were compared for their multivitamin and calcium intake, DRC levels, and other covariates. OUTCOME MEASURES: Odds ratios (OR), adjusted using both crude analysis and multiple logistic regression, were used as measures of association between BC and DRC and other selected variables. RESULTS: The BC group had 30% reduced odds of taking multivitamins and calcium as compared to controls: (1) OR = 0.7 (95% CI, 0.4-1.0; P = .073) for multivitamins and (2) OR = 0.7 (95% CI, 0.4-1.2; P = .167) for calcium. Women with low DRC had 50% lower odds of taking calcium and 30% lower odds of currently taking vitamins OR = 0.5 (95% CI, 0.4-0.7; P = .001) for calcium and (2) OR = 0.7 (95% CI, 0.5-0.9.1; P = .047) for vitamins. CONCLUSIONS: Although this study is a case-control study in which the risk of BC could not be assessed, results suggest that vitamin supplementation could be an independent protective factor for BC. Calcium intake appears to affect DRC in a positive way, because it was associated with a high DRC level, which in turn is associated with low odds for BC.