Regina Santella - Academia.edu (original) (raw)

Papers by Regina Santella

Carolina Digital Repository (University of North Carolina at Chapel Hill), 2009

Polycyclic aromatic hydrocarbons (PAH) are mammary carcinogens in animal studies, and a few epide... more Polycyclic aromatic hydrocarbons (PAH) are mammary carcinogens in animal studies, and a few epidemiologic studies have suggested a link between elevated levels of PAH-DNA adducts and breast cancer incidence. An association between PAH-DNA adducts and survival among breast cancer cases has not been previously reported. We conducted a survival analysis among women with newly diagnosed invasive breast cancer between 1996 and 1997, enrolled in the Long Island Breast Cancer Study Project. DNA was isolated from blood samples that were obtained from cases shortly after diagnosis and before treatment, and assayed for PAH-DNA adducts using an ELISA. Among the 722 cases with PAH-DNA adduct measurements, 97 deaths (13.4%) from all causes and 54 deaths (7.5%) due to breast cancer were reported to the National Death Index (NDI) by December 31, 2002. Using Cox proportional hazards models and controlling for age at diagnosis, we did not find evidence that all-cause mortality (hazard ratio (HR) = 0.88; 95% confidence interval (CI): 0.57-1.37), or breast cancer mortality (HR = 1.20; 95% CI: 0.63-2.28) was strongly associated with detectable PAH-DNA adduct levels compared with non-detectable adducts; additionally, no dose-response association was observed. Among a subgroup with treatment data (n=520), adducts were associated with over a twofold higher mortality among those receiving radiation, but mortality for adducts was reduced among hormone therapy users. Results from this large population-based study do not provide strong support

Carolina Digital Repository (University of North Carolina at Chapel Hill), 2009

Telomeres play a critical role in maintaining the integrity and stability of the genome, and are ... more Telomeres play a critical role in maintaining the integrity and stability of the genome, and are susceptible to oxidative damage after telomere shortening to a critical length. In the present study, we explored the role of white blood cell (WBC) DNA telomere length on breast cancer risk, and examined whether urinary 15-F 2-isoprostanes (15-F 2t-IsoP) and 8-oxo-7,8dihydrodeoxyguanosine (8-oxodG), or dietary antioxidant intake modified the relationship between telomere length and breast cancer risk. A population-based case-control study-the Long Island Breast Cancer Study Project (LIBCSP) was conducted among 1,067 cases and 1,110 controls. Telomere length was assessed by quantitative PCR (Q-PCR). Overall, the mean levels of telomere length (T/S ratio), 15-F 2t-IsoP and 8-oxodG were not significantly different between cases and controls. Among pre-menopausal women only, carrying shorter telomeres (Q3 and Q4), as compared with the longest (Q1), was associated with significantly increased breast cancer risk. Age-adjusted OR and 95%CI were 1.71 (1.10-2.67) and 1.61 (1.05-2.45). The 5-F 2t-IsoP and 8-oxodG biomarkers did not modify the telomere-breast cancer association. A moderate increase in breast cancer risk was observed among women with the shortest telomeres (Q4) and lower dietary and supplemental intake of β-carotene, vitamin C or E intake (OR (95%CI)=1.48 (1.08-2.03), 1.39 (1.01-1.92) and 1.57 (1.14-2.18), respectively), although the trend test exhibited statistical significance only within the lower vitamin E intake subgroup (P trend =0.01). These results provided the strongest evidence to date that breast cancer risk may be affected by telomere length among pre-menopausal women or women with low dietary intake of antioxidants or antioxidant supplements.

Carolina Digital Repository (University of North Carolina at Chapel Hill), 2008

Xeroderma pigmentosum complementation group C (XPC) is an important DNA nuclear excision repair (... more Xeroderma pigmentosum complementation group C (XPC) is an important DNA nuclear excision repair (NER) gene that recognizes the damage caused by variety of bulky DNA adducts. We evaluated the association of two common non-synonymous polymorphisms in XPC (Ala499Val and Lys939Gln) with breast cancer risk in the Long Island Breast Cancer Study Project (LIBCSP), a population-based case-control study. Genotyping of 1,067 cases and 1,110 controls was performed by a high throughput assay with fluorescence polarization. There were no overall associations between XPC polymorphisms and breast cancer risk. A diplotype CC-CC was significantly associated with increased breast cancer risk compared with diplotype CA-CA (OR = 1.4, 95%CI: 1.0-1.9), but was not significant when compared with all other diplotypes combined (OR = 1.22, 95%CI: 0.97-1.53). No modification effects were observed for XPC genotypes by cigarette smoking status, smoking pack years or polycyclic aromatic hydrocarbons (PAH) DNA adducts. The increase in breast cancer risk was slightly more pronounced among women with detectable PAH-DNA adducts and carrying the diplotype CC-CC (OR = 1.6, 95%CI: 1.1-2.2) compared to women with non detectable PAH-DNA adducts carrying other diplotypes combined, but no statistically significant interaction was observed (P interaction = 0.69). These data suggest that XPC have neither independent effects nor interactions with cigarette smoking and PAH-DNA adducts for breast cancer risk. Further studies with multiple genetic polymorphisms in NER pathway are warranted.

Scientific Reports, Mar 1, 2022

DNA repair phenotype can be measured in blood and may be a potential biomarker of cancer risk. We... more DNA repair phenotype can be measured in blood and may be a potential biomarker of cancer risk. We conducted a systematic review and meta-analysis of epidemiological studies of DNA repair phenotype and cancer through March 2021. We used random-effects models to calculate pooled odds ratios (ORs) of cancer risk for those with the lowest DNA repair capacity compared with those with the highest capacity. We included 55 case-control studies that evaluated 12 different cancers using 10 different DNA repair assays. The pooled OR of cancer risk (all cancer types combined) was 2.92 (95% Confidence Interval (CI) 2.49, 3.43) for the lowest DNA repair. Lower DNA repair was associated with all studied cancer types, and pooled ORs (95% CI) ranged from 2.02 (1.43, 2.85) for skin cancer to 7.60 (3.26, 17.72) for liver cancer. All assays, except the homologous recombination repair assay, showed statistically significant associations with cancer. The effect size ranged from 1.90 (1.00, 3.60) for the etoposide-induced double-strand break assay to 5.06 (3.67, 6.99) for the γ-H2AX assay. The consistency and strength of the associations support the use of these phenotypic biomarkers; however large-scale prospective studies will be important for understanding their use related to age and screening initiation. Cancer initiation is classically associated with the induction of mutations in key oncogenes or tumor suppressor genes, due to the presence of unrepaired/misrepaired DNA lesions produced by endogenous or exogenous genotoxic agents 1. Many risk factors for cancer such as smoking, ionizing radiation, and diet can induce DNA damage 2. Higher levels of DNA/protein adducts in blood from exogenous exposures are associated with increased cancer risk 3. DNA repair plays a fundamental role in the maintenance of genomic integrity 4. Individuals with deficiency in DNA repair capacity might be more susceptible to cancer risk. DNA repair capacity can be assessed either with genomic/proteomic approaches or with phenotypic approaches 5. A concern with genomic/proteomic approaches is that mammalian DNA damage repair mechanisms are extraordinarily complex. In humans it involves ~ 450 genes in 13 different pathways including 7 core and 6 associated pathways, with over half the proteins interacting with other proteins from different pathways (Fig. 1) 6 ; it follows that any specific genomic or proteomic methodology is unlikely to reflect overall DNA repair capacity. If it were possible to characterize the genetic complexity, it would be extremely challenging to implement at a clinical level. By contrast, phenotypic approaches-e.g., inducing DNA damage and then measuring the rate of DNA repair or the amount of unrepaired DNA damage, or both-have the potential to be more reflective of overall DNA repair capacity 7. DNA repair phenotyping assays use fresh or cryopreserved peripheral blood mononuclear cells (PBMC) or lymphoblastoid cell lines as a surrogates for target tissue of DNA repair 7. A phenotypic assay, if it is high throughput, may be more feasible to implement in a clinical setting as phenotypic approaches can reflect the totality of multiple complex pathways. The purpose of our systematic review and meta-analysis is to quantitatively and qualitatively summarize the literature regarding DNA repair phenotype and risk of cancer. We assessed the association of DNA repair

Breast Cancer Research and Treatment, Apr 12, 2012

The impact of genetic variants in telomere pathway genes on telomere length and breast cancer sur... more The impact of genetic variants in telomere pathway genes on telomere length and breast cancer survival remains unclear. We hypothesized that telomere length and genetic variants of telomere pathway genes are associated with survival among breast cancer patients. A population-based cohort study of 1,026 women diagnosed with a first primary breast cancer was conducted to examine telomere length and 52 genetic variants of 9 telomere pathway genes. Adjusted Cox regression analysis was employed to examine associations between telomere length, genetic variants and all-cause and breast cancer-specific mortality. Longer telomere length was significantly correlated with all-cause mortality in the subgroup with HER-2/neu negative tumors (HR=1.90, 95%CI: 1.12-3.22). Carrying the PINX1-33 (rs2277130) G-allele was significantly associated with increased all-cause mortality (HR=1.45, 95% CI: 1.06-1.98). Three SNPs (TERF2-03 rs35439397, TERT-14 rs2853677 and TERT-67 rs2853669) were significantly associated with reduced all-cause mortality. A similar reduced trend for breast cancer-specific mortality was observed for carrying the TERT-14 (rs2853677) T-allele (HR=0.57, 95% CI: 0.39-0.84), while carrying the POT1-18 (rs1034794) T-allele significantly increased breast cancer specific-mortality (HR=1.48, 95% CI: 1.00-2.19). However, none of the associations remained significant after correction for multiple tests. A significant dose-response effect was observed with increased number of unfavorable alleles/genotypes (PINX1-33 G-allele, POT1-18 T-allele, TERF2-03 GG, TERT-14 CC, and TERT-67 TT genotypes) and decreased survival. These data suggest that unfavorable genetic variants in telomere pathway genes may help to predict breast cancer survival.

Carolina Digital Repository (University of North Carolina at Chapel Hill), 2015

Purpose-Obesity is associated with increased bioavailability of estrogen, hyperinsulemia and chro... more Purpose-Obesity is associated with increased bioavailability of estrogen, hyperinsulemia and chronic inflammation, all of which may promote tumor growth. Given DNA repair and oxidative stress pathways may work together with these mechanisms to influence carcinogenesis, we

Carolina Digital Repository (University of North Carolina at Chapel Hill), 2016

Mechanisms underlying the poor breast cancer prognosis among obese women are unresolved. DNA meth... more Mechanisms underlying the poor breast cancer prognosis among obese women are unresolved. DNA methylation levels are linked to obesity and to breast cancer survival. We hypothesized that obesity may work in conjunction with the epigenome to alter prognosis. Using a population-based sample of women diagnosed with first primary breast cancer, we examined modification of the obesity-mortality association by DNA methylation. In-person interviews were conducted

Carolina Digital Repository (University of North Carolina at Chapel Hill), 2008

Breast cancer is the second leading cause of cancer mortality among women. Given its important ro... more Breast cancer is the second leading cause of cancer mortality among women. Given its important role in DNA methylation and synthesis, one-carbon metabolism may affect breast cancer mortality. We utilized a population-based cohort of 1,508 women with breast cancer to investigate possible associations of dietary intake of B vitamins prior to diagnosis as well as 9 polymorphisms of onecarbon metabolizing genes and subsequent survival. Women newly diagnosed with a first primary breast cancer in 1996-1997 were followed for vital status for an average of 5.6 years. Kaplan-Meier survival and Cox proportional hazard regression analyses were used to evaluate the association between dietary intakes of B vitamins (1479 cases), genotypes (∼1065 cases) and all-cause as well as breast cancer-specific mortality. We found that higher dietary intake of vitamin B 1 and B 3 was associated with improved survival during the follow-up period (p for trend = 0.01 and 0.04, respectively). Compared to the major genotype, the MTHFR 677 T allele carriers have reduced allcause mortality and breast cancer-specific mortality in a dominant model [HR and 95% CI: 0.69 (0.49-0.98) and 0.58 (0.38-0.89), respectively). The BHMT 742 A allele was also associated with reduced all-cause mortality [HR 0.70(0.50-1.00)]. ER/PR status modified the association between the MTHFR C677T polymorphism and survival (p=0.05). The survival associations with one-carbon polymorphisms did not differ with the use of chemotherapy, although study power was limited for examining such effect modification. Our results indicate that one-carbon metabolism may be an important pathway that could be targeted to improve breast cancer survival.

Carolina Digital Repository (University of North Carolina at Chapel Hill), 2009

Breast cancer is the second leading cancerrelated cause of death among women in the United States... more Breast cancer is the second leading cancerrelated cause of death among women in the United States (American Cancer Society 2008). Previous epidemiologic and experimental investigations suggest that poly cyclic aromatic hydrocarbons (PAHs) may be associated with breast cancer (Bonner et al. 2005; el-Bayoumy et al. 1995; Gammon et al. 2002b, 2004b; Rundle et al. 2000). However, despite strongly positive associations in animal models and some evidence of a positive association in humans, the carcinogenicity of these chemical compounds on the human breast remains unclear. PAHs are ubiquitous environmental pollu tants formed by incomplete combustion of organic material (Samanta et al. 2002). These chemicals have estrogenic properties (Santodonato 1997), are known carcinogens in humans (Samanta et al. 2002), and cause mammary tumors in laboratory animals (el-Bayoumy et al. 1995; Hecht 2002). Exposure to PAHs in the general population occurs primarily through charred, smoked, and broiled foods; leafy vegetables (Phillips 1999); wood-and coal-burning stoves (Lewis et al. 1999); air pollution (Lioy and Greenberg 1990); and tobacco smoke (Besaratinia et al. 2002). PAH-DNA adducts (Gammon et al. 2004b), lifetime intake of grilled/smoked meat (Steck et al. 2007), and long-term passive smoking-but not current or former active smoking (Gammon et al. 2004a)-have been associated with breast cancer in our study population. Cigarette smoke is associated with PAH-DNA adducts in human lymphocytes (Shantakumar et al. 2005), and the PAH benzo[a]pyrene (B[a]P) from cigarette smoke induces neoplastic transformation of human breast epithelial cells (Russo et al. 2002). However, smoking has been inconsistently linked to breast cancer in epidemiologic research, with more consistently positive findings reported for long-term passive smoking and among genetically susceptible subgroups (Ambrosone et al. 2008; Terry and Goodman 2006; Terry and Rohan 2002). PAHs are formed on the surface of "welldone" meat (Kazerouni et al. 2001), but epidemiologic studies examining meat intake or doneness have yielded inconclusive results (Holmes et al. 2003; Zheng et al. 1998). These studies have primarily focused on recent dietary habits, whereas lifetime intake may be more rele vant for carcinogenesis. Steck et al. (2007) observed a positive association between lifetime intake of grilled and smoked meat and breast cancer among post menopausal women [middle vs. lowest tertile of intake, odds ratio (OR) = 1.47; 95% confidence interval (CI), 1.11-1.95; highest vs. lowest tertile of intake, OR = 1.47; 95% CI, 1.12-1.92)]. PAHs are metabolized through activation and detoxification pathways. When PAH exposure is high or detoxification

Environment international, Jan 12, 2016

Despite studies having consistently linked exposure to single-source polycyclic aromatic hydrocar... more Despite studies having consistently linked exposure to single-source polycyclic aromatic hydrocarbons (PAHs) to breast cancer, it is unclear whether single sources or specific groups of PAH sources should be targeted for breast cancer risk reduction. This study considers the impact on breast cancer incidence from multiple PAH exposure sources in a single model, which better reflects exposure to these complex mixtures. In a population-based case-control study conducted on Long Island, New York (N=1508 breast cancer cases/1556 controls), a Bayesian hierarchical regression approach was used to estimate adjusted posterior means and credible intervals (CrI) for the adjusted odds ratios (ORs) for PAH exposure sources, considered singly and as groups: active smoking; residential environmental tobacco smoke (ETS); indoor and outdoor air pollution; and grilled/smoked meat intake. Most women were exposed to PAHs from multiple sources, and the most common included active/passive smoking and gr...

The FASEB Journal, 2009

Alta ingestão de betaína e colina diminui a frequência e a mortalidade do câncer de mama

International Journal of Cancer, 2013

The mechanisms driving the inverse association between recreational physical activity (RPA) and b... more The mechanisms driving the inverse association between recreational physical activity (RPA) and breast cancer risk are complex. While exercise is associated with increased reactive oxygen species production it may also improve damage repair systems, particularly those that operate on single-strand breaks including base excision repair (BER), nucleotide excision repair (NER) and mismatch repair (MMR). Of these repair pathways, the role of MMR in breast carcinogenesis is least investigated. Polymorphisms in MMR or other DNA repair gene variants may modify the association between RPA and breast cancer incidence. We investigated the individual and joint effects of variants in three MMR pathway genes (MSH3, MLH1 and MSH2) on breast cancer occurrence using resources from the Long Island Breast Cancer Study Project. We additionally characterized interactions between RPA and genetic polymorphisms in MMR, BER and NER pathways. We found statistically significant multiplicative interactions (p<0.05) between MSH2 and MLH1, as well as between postmenopausal RPA and four variants in DNA repair (XPC-Ala499Val, XPF-Arg415Gln, XPG-Asp1104His and MLH1-lle219Val). Significant risk reductions were observed among highly active women with the common genotype for XPC (OR=0.54; 95% CI, 0.36-0.81) and XPF (OR=0.62; 95% CI, 0.44-0.87), as well as among active women who carried at least one variant allele in XPG (OR=0.46; 95% CI, 0.29-0.77) and MLH1

Epidemiology, 2007

Background: Polycyclic aromatic hydrocarbons (PAHs) and heterocyclic amines (HCAs) are carcinogen... more Background: Polycyclic aromatic hydrocarbons (PAHs) and heterocyclic amines (HCAs) are carcinogens formed in or on the surface of well-done meat, cooked at high temperature. Methods: We estimated breast cancer risk in relation to intake of cooked meat in a population-based, case-control study (1508 cases and 1556 controls) conducted in Long Island, NY from 1996 to 1997. Lifetime intakes of grilled or barbecued and smoked meats were derived from the interviewer-administered questionnaire data. Dietary intakes of PAH and HCA were derived from the selfadministered modified Block food frequency questionnaire of intake 1 year before reference date. Unconditional logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Results: Modest increased risk was observed among postmenopausal, but not premenopausal, women consuming the most grilled or barbecued and smoked meats over the life course (OR ϭ 1.47; CI ϭ 1.12-1.92 for highest vs. lowest tertile of intake). Postmenopausal women with low fruit and vegetable intake, but high lifetime intake of grilled or barbecued and smoked meats, had a higher OR of 1.74 (CI ϭ 1.20-2.50). No associations were observed with the food frequency questionnaire-derived intake measures of PAHs and HCAs, with the possible exception of benzo(␣)pyrene from meat among postmenopausal women whose tumors were positive for both estrogen receptors and progesterone receptors (OR ϭ 1.47; CI ϭ 0.99-2.19). Conclusions: These results support the accumulating evidence that consumption of meats cooked by methods that promote carcinogen formation may increase risk of postmenopausal breast cancer.

Cancer Epidemiology, Biomarkers & Prevention, 2008

Cancer Causes & Control, 2012

Purpose-The mechanisms driving the physical activity-breast cancer association are unclear. Exerc... more Purpose-The mechanisms driving the physical activity-breast cancer association are unclear. Exercise both increases reactive oxygen species production, which may transform normal epithelium to a malignant phenotype, and enhances antioxidant capacity, which could protect against subsequent oxidative insult. Given the paradoxical effects of physical activity, the oxidative stress pathway is of interest. Genetic variation in CAT or antioxidant-related polymorphisms may mediate the physical activity-breast cancer association. Methods-We investigated the main and joint effects of three previously unreported polymorphisms in CAT on breast cancer risk. We also estimated interactions between recreational physical activity (RPA) and 13 polymorphisms in oxidative stress-related genes. Data were from the Long Island Breast Cancer Study Project, with interview and biomarker data available on 1,053 cases and 1,102 controls. Results-Women with ≥1 variant allele in CAT rs4756146 had a 23 % reduced risk of postmenopausal breast cancer compared with women with the common TT genotype (OR = 0.77; 95 % CI = 0.59-0.99). We observed two statistical interactions between RPA and genes in the anti-oxidant pathway (p = 0.043 and 0.006 for CAT and GSTP1, respectively). Highly active women harboring variant alleles in CAT rs1001179 were at increased risk of breast cancer compared with women with the common CC genotype (OR = 1.61; 95 % CI, 1.06-2.45). Risk reductions were observed among moderately active women carrying variant alleles in GSTP1 compared with women homozygous for the major allele (OR = 0.56; 95 % CI, 0.38-0.84). Conclusions-Breast cancer risk may be jointly influenced by RPA and genes involved in the antioxidant pathway, but our findings require confirmation.

European Journal of Cancer, May 1, 2018

Background-Hepatocarcinogenicity of Aflatoxin B 1 (AFB 1) has rarely been studied in populations ... more Background-Hepatocarcinogenicity of Aflatoxin B 1 (AFB 1) has rarely been studied in populations with hepatitis C virus (HCV) infection and those without hepatitis B virus (HBV) and HCV infection (non-B-non-C). This case-control study nested in a community-based cohort aimed to investigate the HCC risk associated with AFB 1 in HCV-infected and non-B-non-C participants. Methods-Baseline serum AFB 1-albumin adduct levels were measured in 100 HCC cases and 1767 controls seronegative for anti-HCV and HBsAg (non-B-non-C), and another 103 HCC cases

Environmental Health, Dec 1, 2014

Background: Previous studies suggest that polycyclic aromatic hydrocarbons (PAHs) may adversely a... more Background: Previous studies suggest that polycyclic aromatic hydrocarbons (PAHs) may adversely affect breast cancer risk. Indoor air pollution from use of indoor stoves and/or fireplaces is an important source of ambient PAH exposure. However, the association between indoor stove/fireplace use and breast cancer risk is unknown. We hypothesized that indoor stove/fireplace use in a Long Island, New York study population would be positively associated with breast cancer and differ by material burned, and the duration and timing of exposure. We also hypothesized that the association would vary by breast cancer subtype defined by p53 mutation status, and interact with glutathione S-transferases GSTM1, T1, A1 and P1 polymorphisms. Methods: Population-based, case-control resources (1,508 cases/1,556 controls) were used to conduct unconditional logistic regression to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). Results: Breast cancer risk was increased among women reporting ever burning synthetic logs (which may also contain wood) in their homes (OR = 1.42, 95% CI 1.11, 1.84), but not for ever burning wood alone (OR = 0.93, 95% CI 0.77, 1.12). For synthetic log use, longer duration >7 years, older age at exposure (>20 years; OR = 1.65, 95% CI 1.02, 2.67) and 2 or more variants in GSTM1, T1, A1 or P1 (OR = 1.71, 95% CI 1.09, 2.69) were associated with increased risk. Conclusions: Burning wood or synthetic logs are both indoor PAH exposure sources; however, positive associations were only observed for burning synthetic logs, which was stronger for longer exposures, adult exposures, and those with multiple GST variant genotypes. Therefore, our results should be interpreted with care and require replication.

European Journal of Cancer, Mar 1, 2008

International Journal of Cancer, Apr 6, 2016

Vehicular traffic polycyclic aromatic hydrocarbons (PAHs) have been associated with breast cancer... more Vehicular traffic polycyclic aromatic hydrocarbons (PAHs) have been associated with breast cancer incidence in epidemiologic studies, including our own. Because PAHs damage DNA by forming adducts and oxidative lesions, genetic polymorphisms that alter DNA repair capacity may modify associations between PAH-related exposures and breast cancer risk. Our goal was to examine the association between vehicular traffic exposure and breast cancer incidence within strata of a panel of nine biologically plausible nucleotide excision repair (NER) and base excision repair (BER) genotypes. Residential histories of 1,508 cases and 1,556 controls were assessed in the Long Island Breast Cancer Study Project between 1996 and 1997 and used to reconstruct residential traffic exposures to benzo[a]pyrene, as a proxy for traffic-related PAHs. Likelihood

Carolina Digital Repository (University of North Carolina at Chapel Hill), 2009

Carolina Digital Repository (University of North Carolina at Chapel Hill), 2008

Scientific Reports, Mar 1, 2022

Breast Cancer Research and Treatment, Apr 12, 2012

Carolina Digital Repository (University of North Carolina at Chapel Hill), 2015

Carolina Digital Repository (University of North Carolina at Chapel Hill), 2016

Carolina Digital Repository (University of North Carolina at Chapel Hill), 2008

Carolina Digital Repository (University of North Carolina at Chapel Hill), 2009

Environment international, Jan 12, 2016

The FASEB Journal, 2009

Alta ingestão de betaína e colina diminui a frequência e a mortalidade do câncer de mama

International Journal of Cancer, 2013

Epidemiology, 2007

Cancer Epidemiology, Biomarkers & Prevention, 2008

Cancer Causes & Control, 2012

European Journal of Cancer, May 1, 2018

Environmental Health, Dec 1, 2014

European Journal of Cancer, Mar 1, 2008

International Journal of Cancer, Apr 6, 2016