Latin America and the Caribbean Code Against Cancer 1st Edition: 17 cancer prevention recommendations to the public and to policy-makers (World Code Against Cancer Framework).

Preventable risk factors are responsible of at least 40% of cases and almost 45% of all cancer deaths worldwide. Cancer is already the leading cause of death in almost half of the Latin American and the Caribbean countries constituting a public health problem. Cost-effective measures to reduce exposures through primary prevention and screening of certain types of cancers are critical in the fight against cancer but need to be tailored to the local needs and scenarios. The Latin America and the Caribbean (LAC) Code Against Cancer, 1st edition, consists of 17 evidence-based recommendations for the general public, based on the most recent solid evidence on lifestyle, environmental, occupational, and infectious risk factors, and medical interventions. Each recommendation is accompanied by recommendations for policymakers to guide governments establishing the infrastructure needed to enable the public adopting the recommendations. The LAC Code Against Cancer has been developed in a collaborative effort by a large number of experts from the region, under the umbrella strategy and authoritative methodology of the World Code Against Cancer Framework. The Code is a structured instrument ideal for cancer prevention and control that aims to raise awareness and educate the public, while building capacity and competencies to policymakers, health professionals, stakeholders, to contribute to reduce the burden of cancer in LAC.

Socioeconomic, Clinical, and Molecular Features of Breast Cancer Influence Overall Survival of Latin American Women.

Molecular profile of breast cancer in Latin-American women was studied in five countries: Argentina, Brazil, Chile, Mexico, and Uruguay. Data about socioeconomic characteristics, risk factors, prognostic factors, and molecular subtypes were described, and the 60-month overall cumulative survival probabilities (OS) were estimated. From 2011 to 2013, 1,300 eligible Latin-American women 18 years or older, with a diagnosis of breast cancer in clinical stage II or III, and performance status ≦̸1 were invited to participate in a prospective cohort study. Face-to-face interviews were conducted, and clinical and outcome data, including death, were extracted from medical records. Unadjusted associations were evaluated by Chi-squared and Fisher's exact tests and the OS by Kaplan-Meier method. Log-rank test was used to determine differences between cumulative probability curves. Multivariable adjustment was carried out by entering potential confounders in the Cox regression model. The OS at 60 months was 83.9%. Multivariable-adjusted death hazard differences were found for women living in Argentina (2.27), Chile (1.95), and Uruguay (2.42) compared with Mexican women, for older (≥60 years) (1.84) compared with younger (≤40 years) women, for basal-like subtype (5.8), luminal B (2.43), and HER2-enriched (2.52) compared with luminal A subtype, and for tumor clinical stages IIB (1.91), IIIA (3.54), and IIIB (3.94) compared with stage IIA women. OS was associated with country of residence, PAM50 intrinsic subtype, age, and tumor stage at diagnosis. While the latter is known to be influenced by access to care, including cancer screening, timely diagnosis and treatment, including access to more effective treatment protocols, it may also influence epigenetic changes that, potentially, impact molecular subtypes. Data derived from heretofore understudied populations with unique geographic ancestry and sociocultural experiences are critical to furthering our understanding of this complexity.

Time trends and age-period-cohort analysis of cervical cancer mortality rate in Brazil.

BACKGROUND: Cervical cancer (CC) is a common preventable and curable disease that may lead to death. Our aim was to describe the patterns of time trends in CC mortality rates among women in Brazil from 1980 to 2017, and identify the influence of age, period and birth cohort (APC) stratified by region (North NR, Northeast NER, Southeast SER, South SR, Center-Western region CWR). METHODS: We performed a time-series analysis using secondary data bases. Crude (MR) and WHO age-standardized CC mortality rates (aMR) were estimated per 100,000 women. We evaluated time trends using permutation joinpoint regression models (JP) and APC models to estimate the effect of APC on MR. RESULTS: The JP analysis showed a temporal decrease in all regions, except the NR, which had an annual percentage increase of 0.44 (95%CI 0.2 - 0.7). MR in the NR was 2 to 4 times higher than in the other regions. We observed steady increases in MR with age in the NR and NER. A plateau after age 40 was observed in SER, SR, and CWR. The NR and NER MR ratio stabilized around the year 2000. Birth cohort effect showed decreasing MR ratio from 1900 to 1970 for all regions, except the NR, which showed increasing MR rate from older to more recent cohorts. CONCLUSION: We showed relevant differences in cervical MR by region, which may reflect inequality in access to primary and secondary prevention as well as treatment, particularly in the NR.

Factors associated with cervical intraepithelial neoplasia (CIN2/CIN3), early stage and advanced stage of cervical cancer diagnosis in the Brazilian Amazonian region.

To understand the impact of demographic, behavioral and contextual factors on cervical cancer, we examined the profile of women classified according to cervical cancer staging [precursor lesions cervical intraephitelial neoplasia (CIN2/CIN3), early- and advanced-stage cancer]. Patients were identified in the main oncological reference hospital in Pará State, Brazil, from 2013 through 2015. Adjusted prevalence ratios and their respective 95% confidence intervals were estimated using Poisson regression with robust variance. The study included 172 cases of CIN2/CIN3 lesions, 158 of early stage and 552 of advanced stage of cervical cancer. The proportion of gynecological complaints as a reason for clinic visit was 2.3 times higher among patients at an early stage compared with patients with CIN2/CIN3 lesions. Compared with early-stage cancer groups, the prevalence of advanced-stage cancer was higher among older patients, those without paid activity (adjusted prevalence ratio = 1.15; confidence interval 95%: 1.03-1.29), those who never had a Pap test (adjusted prevalence ratio = 1.23; confidence interval 95%: 1.08-1.40), those who were seen at the hospital clinic due to gynecological complaints (adjusted prevalence ratio = 1.48; confidence interval 95%: 1.19-1.85) and those who underwent biopsy in the private care system (adjusted prevalence ratio = 1.12; confidence interval 95%: 1.02-1.22). These differences seem to reflect problems in the health system, low socioeconomic level and poor awareness of the importance of Pap tests among those with a diagnosis of advanced-stage cervical cancer.

Breast Cancer Quality of Life and Health-state Utility at a Brazilian Reference Public Cancer Center.

Objectives: To evaluate health-related-quality-of-life and derive health-state-utility (HSU) from breast cancer patients, before and after routine therapy at a Brazilian reference public cancer center.Methods: In a prospective cohort study, a consecutive sample of outpatients newly diagnosed with breast cancer was submitted to two interviews (baseline, 6-month) to complete EQ-5D-3L/VAS and EORTC-QLQ-C30/BR23 questionnaires. Demographic and clinical information was reviewed from medical records.Results: For 196 patients, EQ-5D domains of pain/discomfort and anxiety/depression were mainly affected, but partially improved overtime, while mobility/usual activities/self-care worsened after therapy. EORTC-QLQ-C30/BR23 scales mostly affected were emotional functioning, insomnia, pain, sexual enjoyment and future self-health perspective at baseline, while financial difficulties, insomnia, fatigue and therapy side-effects at follow-up. Overtime mean scores were 71.4 (95%CI68.5-74.4) and 76.1 (95%CI73.3-78.8) for EQ-5D-VAS, and 0.712 (95%CI0.686-0.737) and 0.732 (95%CI0.707-0.757) for HSU. HSU was 0.689 (95%CI0.648-0.730) in stages III-IV, and 0.692 (95%CI0.652-0.731) under two/three chemotherapy regimens.Conclusion: In a context of impairments in emotional functioning, sexual enjoyment, symptoms burden, and poor future self-health perspective, breast cancer produced a mean HSU of 0.712. After routine care, there was a small improvement in quality of life, with lower HSU particularly in advanced disease and multiple chemotherapy regimens.

Smoke-free legislation and neonatal and infant mortality in Brazil: longitudinal quasi-experimental study.

OBJECTIVE: To examine the associations of partial and comprehensive smoke-free legislation with neonatal and infant mortality in Brazil using a quasi-experimental study design. DESIGN: Monthly longitudinal (panel) ecological study from January 2000 to December 2016. SETTING: All Brazilian municipalities (n=5565). PARTICIPANTS: Infant populations. INTERVENTION: Smoke-free legislation in effect in each municipality and month. Legislation was encoded as basic (allowing smoking areas), partial (segregated smoking rooms) or comprehensive (no smoking in public buildings). Associations were quantified by immediate step and longer term slope/trend changes in outcomes. STATISTICAL ANALYSES: Municipal-level linear fixed-effects regression models. MAIN OUTCOMES MEASURES: Infant and neonatal mortality. RESULTS: Implementation of partial smoke-free legislation was associated with a -3.3 % (95% CI -6.2% to -0.4%) step reduction in the municipal infant mortality rate, but no step change in neonatal mortality. Comprehensive smoke-free legislation implementation was associated with -5.2 % (95% CI -8.3% to -2.1%) and -3.4 % (95% CI -6.7% to -0.1%) step reductions in infant and neonatal mortality, respectively, and a -0.36 (95% CI -0.66 to-0.06) annual decline in the infant mortality rate. We estimated that had all smoke-free legislation introduced since 2004 been comprehensive, an additional 10 091 infant deaths (95% CI 1196 to 21 761) could have been averted. CONCLUSIONS: Strengthening smoke-free legislation in Brazil is associated with improvements in infant health outcomes-particularly under comprehensive legislation. Governments should accelerate implementation of comprehensive smoke-free legislation to protect infant health and achieve the United Nation's Sustainable Development Goal three.

Patient Preferences for Breast Cancer Treatment Interventions: A Systematic Review of Discrete Choice Experiments.

INTRODUCTION: Understanding how patients value different characteristics of an intervention and make trade-offs in a therapy choice context with potential benefit and possible harm may result in decisions for which a better reflected value is delivered. This systematic review summarizes patient preferences for breast cancer treatments elicited by discrete choice experiments (DCE). METHODOLOGY: The electronic databases MEDLINE (PubMed), Scopus, PsycINFO, CINAHL, LILACS, and Web of Science were last searched on May 9, 2019 without restrictions regarding language and time of publication. Original studies reporting patient preferences related to breast cancer treatment (surgery, radiotherapy, endocrine therapy, chemotherapy or palliative care) elicited by DCE were eligible. A narrative synthesis of the relative importance and trade-offs of the treatment attributes of each study was reported. RESULTS: Five studies conducted in Japan, Thailand, USA and the Netherlands with 146-298 participants evaluated preferences regarding chemotherapy regimens for advanced/metastatic disease, and breast reconstruction after mastectomy. The attributes with major relative effects on preferences were greater survival, better aesthetic result of the surgery, and lower side effects and complication rates. Patients would trade a better aesthetic result to minimize complication rates, and, in advanced disease, the willingness to pay was greater for gains in survival and to avoid some severe adverse events. CONCLUSION: Despite the relative lack of evidence in this specific context, our review shows that breast cancer patients naturally value greater benefit and, in scenarios of advanced and metastatic disease, are willing to face risks of some side effects for gains in survival.

Electronic cigarettes and narghile users in Brazil: Do they differ from cigarettes smokers?

BACKGROUND: Cigarette smoking prevalence is declining, however, other tobacco products have emerged recently, such as electronic cigarettes (e-cigarettes) and narghile (hookah/shisha/waterpipe). Narghile sales are not prohibited in Brazil, but e-cigarettes are. Accurate estimates of such products are key for proper monitoring and control. OBJECTIVE: To describe the prevalence of e-cigarettes and narghile use and to investigate whether sociodemographic characteristics of individuals who are using these products differ from those who are using manufactured cigarettes. METHODS: Using a nationally representative sample survey of Brazilians aged 12-65 years in 2015, we estimated the prevalence rates of each tobacco products within the last 12-months, stratified by macro-region, municipality size, sex-at-birth, sexual orientation, color/race, age-group, and monthly income. Multivariable logistic models were fitted to understand determinants of each tobacco product use, considering the complex sample design. RESULTS: E-cigarette, narghile, and cigarette prevalence rates were estimated at 0.43%, 1.65% and 15.35%, respectively, corresponding to around 0.6million e-cigarette users, 2.5 million narghile users and 23.5 million cigarette users. Non-heterosexual individuals were a most-at-risk group for both e-cigarette/narghile and cigarette use. Despite similarities, e-cigarette/narghile users were younger and had higher socioeconomic status than cigarette users. Additional analyses showed that recent cigarette use seems to be more associated with e-cigarette/narghile use among youth than among adults. CONCLUSIONS: Our findings may provide valuable information about e-cigarette/narghile use in Brazil. Prevention strategies targeted to youth to both narghile and e-cigarettes use should be implemented together, which might be one strategy to prevent the emergency of a new generation of smokers in Brazil.

Is a Family History of the Breast Cancer Related to Women's Cancer Prevention Behaviors?

Families share behavioral risk factors that can increase the risk of cancer development. We examined whether having a positive family breast cancer history is associated with health behaviors/screening practices. Analyses were based on a cross-sectional sample of 545 Brazilian National Cancer Institute Hospital patients with newly diagnosed breast cancer in 2013/2014. Women were categorized according to their breast cancer family history. Age-adjusted Poisson regressions with robust variance were performed to estimate the association between breast cancer family history and selected health-related behaviors and screening practices. About one fourth of women reported a positive family history of breast cancer. Contrary to expectation, we found that women with a family history of breast cancer did not report healthier behaviors more often than those without a family history. However, those with a family history were more likely to report a mammographic exam prior to the mammographic diagnosis. Our study suggests that having a family history of cancer is not sufficient to change women's behaviors about physical activity, weight control and diet, smoking, and drinking, but it seems to influence their breast cancer screening behavior. Our results suggest the need to increase women's information and/or understanding that healthier lifestyles contribute to cancer prevention.

HPV DNA methylation at the early promoter and E1/E2 integrity: A comparison between HPV16, HPV18 and HPV45 in cervical cancer.

OBJECTIVES: To compare and describe type-specific characteristics of HPV16, HPV18 and HPV45 in cervical cancer with respect to 3'LCR methylation and disruption of E1/E2. METHODS: The methylation level of 137 cervical cancer samples (70 with HPV16, 37 with HPV18, and 30 with HPV45) of Brazilian patients was analyzed by pyrosequencing. PCR amplifications were performed to characterize E1 and E2 disruption as an episomal surrogate. RESULTS: The 3'LCR of HPV16 showed a higher methylation at all CpG sites (7%, 9%, 11%, 10% and 10%) than homologous HPV18 regions (4%, 5%. 6%, 9% and 5%) and HPV45 regions (7%, 7% and 5%). Presence of intact E1/E2 was associated with higher HPV16 and HPV18 methylation levels at all CpG sites (p < 0.05). Disruption of E1/E2 was more frequently found in HPV45 (97%) and HPV18 (84%) than in HPV16 DNA (30%). HPV16 disruption was more frequently found in E1 (48%) unlike HPV18, where it was found in E2 (61%). Concomitant disruption of E1/E2 was most frequent in HPV45 (72%). CONCLUSIONS: The findings showed a higher methylation associated with intact E1/E2 for HPV16 and HPV18. The closely phylogenetic related HPV18 and HPV45 share a similar methylation level and the frequency of viral genome disruption.

Assessing the relationship between smoking and abdominal obesity in a National Survey of Adolescents in Brazil.

Abdominal obesity is even a stronger risk factor than overall obesity for noncommunicable chronic diseases. We examined the association between smoking and abdominal obesity among adolescents. Analyses were based on 38,813 subjects aged 15-17 years from the Study of Cardiovascular Risks in Adolescents (ERICA), a Brazilian school-based national survey. Abdominal obesity was defined considering waist circumference (WC) percentiles. Statistical analyses, stratified by sex, considered the sample complex design. Poisson regression with robust variance was used to estimate smoker-to-nonsmoker abdominal obesity prevalence ratio (PR), adjusting by sociodemographic and lifestyle variables. Higher prevalence of abdominal obesity was observed among adolescents who consumed >1 cigarettes/day, comparing to nonsmokers: considering WC >80th percentile, adjusted-PR for boys was 1.27 [95%CI:1.05,1.52] and, for girls, 1.09 [95%CI:1.00,1.19]; using the 90th percentile, adjusted-PR were 2.24 [95%CI:1.70,2.94] and 1.27 [95%CI:1.12,1.46], respectively for male and female adolescents. Our findings suggest a positive association between cigarette consumption and the prevalence of abdominal obesity, for both boys and girls. Although other studies had found this association in adults, our study contributes to this discussion by assessing it in adolescents using a nationwide representative sample of medium and large municipalities.

Estimating the size of illicit tobacco consumption in Brazil: findings from the global adult tobacco survey.

BACKGROUND: Brazil experienced a large decline in smoking prevalence between 2008 and 2013. Tax rate increases since 2007 and a new tobacco tax structure in 2012 may have played an important role in this decline. However, continuous tax rate increases pushed up cigarette prices over personal income growth and, therefore, some consumers, especially lower income individuals, may have migrated to cheaper illicit cigarettes. OBJECTIVE: To use tobacco surveillance data to estimate the size of illicit tobacco consumption before and after excise tax increases. METHODS: We defined a threshold price and compared it with purchasing prices obtained from two representative surveys conducted in 2008 and 2013 to estimate the proportion of illicit cigarette use among daily smokers. Generalised linear model was specified to understand whether the absolute difference in proportions over time differed by sociodemographic groups and consumption levels. Our findings were validated using an alternative method. RESULTS: Total proportion of illicit daily consumption increased from 16.6% to 31.1% between 2008 and 2013. We observed a pattern of unadjusted absolute decreases in cigarette smoking prevalence and increases in the proportion of illicit consumption, irrespective of gender, age, educational level, area of residence and amount of cigarettes consumed. CONCLUSIONS: The strategy of raising taxes has increased government revenues, reduced smoking prevalence and resulted in an increased illicit trade. Surveillance data can be used to provide information on illicit tobacco trade to help in the implementation of WHO Framework Convention on Tobacco Control (FCTC) article 15 and the FCTC Protocol to Eliminate Illicit Trade in Tobacco Products.

Understanding the relationship between sales of legal cigarettes and deaths: A case-study in Brazil.

Brazil has experienced a large decline in cigarette consumption in the last 25years. However, the most recent annual reports from the tobacco industry market leader in Brazil did not show a decrease in its gross profits. This is particularly important because tobacco industry donations/sponsorships come directly from the industry's reported gross-profits and are used to subvert health policies. The aim of the present study was to estimate (i) tobacco industry's gross-profit from legal cigarettes sales, and (ii) all-cause smoking-attributable deaths (SADs) among current Brazilian smokers who consumed legal cigarettes in 2013. We collected information on prevalence of legal cigarette use, cigarette consumption, price per cigarette pack among individuals aged ≥35years from the Global Adult Tobacco Survey, legal cigarettes sales (e.g., average costs and total volume of sales) provided by the Federal Secretariat of Revenues, and population mortality from the available vital statistics. With a gross-profit of US$1.378 billion (1.307-1.434) from sales of 54.6 billion sticks of cigarettes (53.4-55.5) to 8,424,510 smokers aged 35years and older in Brazil in 2013, cumulative SADs were estimated at 96,012 (85,647-107,654) (around 34% of cumulative SADs also including current smoking of illegal cigarettes and past smoking), i.e., one SAD was equivalent to a gross-profit of US$14,352 (12,140-16,743). Our results revealed the association between sales of cigarettes, gross-profits, and deaths in Brazil. As tobacco industry donations/sponsorships originate from industry's gross profits, which, in turn, depend on cigarette sales, our findings may be useful for increasing "moral pressure" on individuals and institutions and help countries in stopping tobacco industry interference in health policies.

Do more graphic and aversive cigarette health warning labels affect Brazilian smokers' likelihood of quitting?

Between 2008 and 2013, Brazil experienced a large decline in smoking prevalence, with an innovative round of aversive pictorial health warnings implemented on cigarette packs and at points of sale in 2009. The objective of this study was to examine changes over time in the distribution of quitting attempts and self-reported thoughts about quitting due to health warnings among current smokers. We conducted a pre-post study to evaluate data from two nationally-representative surveys conducted in 2008 and 2013. Responses to questions on smokers' quitting attempts in the last year (yes vs. no) and whether health warnings led them to think about quitting in the last month (yes vs. no) were combined into four categories, for which the distribution of the Brazilian smoking population by year was estimated. A multinomial model was used to obtain proportions for each category, adjusted by socio-demographic variables and nicotine dependence. The proportion of smokers who reported making a quitting attempt in the last year and stated that health warnings led them think about quitting smoking statistically increased over time (from 30.0% to 33.1%; p-value=0.010). The percentage of those who answered "no" to these two questions also increased over time (from 23.5% to 32.9%; p-value≤0.001). These findings suggest that innovative warnings introduced in Brazil likely served as a "reminder" for continuing to think about cessation among those who attempted to quit in the last year. These warnings may have also triggered more avoidance of thinking about their contents than the previous warnings, which some studies have found to promote subsequent quitting activity.

Genetic diversity of HPV16 and HPV18 in Brazilian patients with invasive cervical cancer.

Cervical cancer is the fourth most common cancer among women, and ∼70-80% of these cancers are associated with two human papillomavirus types: HPV16 and HPV18. Several studies have reported that intra-type diversity is associated with the progression of infection to invasive cancer. Herein, we report the genetic diversity of HPV16 and HPV18 in a cohort of 594 Brazilian women with invasive cervical cancer and describe the prevalence of lineages and intra-type diversity prior to the implementation of the public immunization program in Brazil. HPV detection and genotyping were performed using PCR, PGMY/GP primers, and DNA extracted from fresh tumors. The HPV16 (378 women) and HPV18 (80 women) lineages were identified by PCR and sequencing of the LCR and E6 fragments, followed by SNV comparison and phylogenetic analysis. In our cohort, was found a higher frequency of the lineage A (in 217 women), followed by lineage D (in 97 women) and lineages B and C (in 10 women each) for HPV16; and a higher frequency of lineage A (in 56 women) followed by lineage B (in 15 women) in HPV18. The genetic diversity of HPV16 indicated a recent expansion of specific variants or a selective advantage that is associated with invasive cancer; this pattern was not observed for HPV18.

Smokers in Brazil: who are they?

BACKGROUND: Brazil has experienced a large decline in smoking prevalence due to several tobacco control policies that were implemented in the past 25 years. Previous population-wide studies found a consistent reduction over time in daily cigarette consumption among all socioeconomic groups. OBJECTIVE: To examine changes between 2008 and 2013 in tobacco behaviours and health-related conditions of smokers. METHODS: We used data obtained from two nationally-representative surveys conducted in 2008 and 2013 to estimate the prevalence of self-reported psychological and physical morbidity, and nicotine dependence markers, stratified by gender and sociodemographic groups. Generalised linear models were used to understand whether absolute differences in prevalence rates over time differed by categories of selected variables. RESULTS: For both genders, as smoking prevalence declined in Brazil, there has been an increase in the proportion of ever smokers who have quit. In addition, remaining smokers seem to be making more quitting attempts. Among men with low educational level or younger than 25 years-old, as compared to their counterparts, cessation rate showed an even greater increase over time. Moreover, the proportion of light smokers, which represent the vast majority of smokers, did not decrease. The percentage of poor health-conditions among remaining smokers nevertheless increased, particularly among women, which can make future cessation more challenging. CONCLUSIONS: In Brazil, quitting rate is increasing, thus suggesting that tobacco control interventions implemented in Brazil in the past years seem to be effectively reaching the smoking population. This is strong evidence against the 'hardening hypothesis', which posits that remaining smokers decrease their willingness and ability to quit.

The association between scheduling a gynecologic clinical visit and clinical breast examination in Rio de Janeiro.

OBJECTIVE: To investigate factors associated with gynecology health professionals' failure to perform clinical breast examinations (CBEs) during clinical visits. METHODS: A cross-sectional, interview-based survey was conducted in 2010 among women aged at least 18 years who had undergone a cervical smear in 2007 at primary-care units in Rio de Janeiro, Brazil. Binomial regression was used to generate prevalence ratios and absolute differences between visits for routine examinations or gynecologic complaints. RESULTS: Analyses included 982 women, of whom 182 (18.5%) did not have a CBE during their visit. Significant interactions were observed between age and primary reason for the visit: the prevalence ratio for no CBE during a visit for gynecologic complaints versus routine examination was 3.2 for women aged at least 40 years, and 1.3 among younger women (P for multiplicative interaction=0.001). Absolute differences were 6.4% and 18.5% for younger and older women, respectively (P for additive interaction=0.04). CONCLUSION: A high proportion of eligible women do not undergo a CBE during cervical smear appointments at primary-care units in Rio de Janeiro, particularly older women presenting with gynecologic complaints. Understanding of health professionals' barriers to following and implementing guidelines for secondary prevention of breast cancer is urgently needed.

Smoking and adverse maternal and child health outcomes in Brazil.

INTRODUCTION: Numerous studies from high-income countries document the causal relationship between cigarette smoking during pregnancy and adverse maternal and child health (MCH) outcomes. Less research has been conducted in low and middle income countries, but a burgeoning literature can be found for Brazil. METHODS: We review Brazilian studies of the prevalence of maternal smoking, the relative risk of smoking-attributable adverse MCH outcomes, and present new estimates for these outcomes, using the attributable fraction method. RESULTS: We found that Brazilian studies of the relative risks of smoking-attributable adverse MCH outcomes were broadly consistent with previous reviews. Based on a comparison of maternal smoking over time, smoking during pregnancy has declined by about 50% over the last 20 years in Brazil. For 2008, we estimate that 5,352 cases of spontaneous abortion, 10,929 cases of preterm birth, 20,717 cases of low birth weight, and 29 cases of sudden infant death syndrome are attributable to maternal smoking. Between 1989 and 2008, the percent of smoking-attributable adverse MCH outcomes in Brazil was at least halved. CONCLUSIONS: The results show that over a 20-year period, during which Brazil implemented numerous effective tobacco control measures, the country experienced a dramatic decrease in both maternal smoking prevalence and smoking-attributable adverse MCH outcomes. Countries that implement effective tobacco control measures can expect to reduce both maternal smoking and adverse MCH outcomes, thereby improving the public health.

Screening of RB1 alterations in Brazilian patients with retinoblastoma and relatives with retinoma: phenotypic and genotypic associations.

PURPOSE: To identify constitutional alterations of the retinoblastoma 1 gene (RB1) in two cohorts of Brazilian patients with retinoblastoma and to analyze genotype-phenotype associations. METHODS: Molecular screening was carried out by direct sequencing of the 27 RB1 exons and flanking regions in blood DNA of 71 patients with retinoblastoma and 4 relatives with retinoma, and with multiplex ligation-dependent probe amplification (MLPA) in 21 patients. The presumed impact of nucleotide substitutions on the structure of the retinoblastoma protein (pRB) was predicted by Polymorphism Phenotyping-2 (PolyPhen-2). Kaplan-Meier and log-rank test were used for estimating 60-month survival rates. RESULTS: One hundred two nucleotide substitutions were detected, 92 substitutions in 59 patients with retinoblastoma and 10 substitutions in 4 individuals with retinoma. Eight substitutions were novel. The majority of substitutions were intronic (86.2%). More than one substitution was present in 37.3% of patients. Twenty-one duplications and 11 deletions were found in 12 patients; some of which with both types of alterations. Duplications/deletions were found in four patients lacking constitutional alterations when analyzed by sequencing, and in eight patients carrying one or more polymorphic intronic substitutions. The global 60-month survival rate in patients was 91.8% (Confidence Interval95% = 85.0 - 99.1). Significant, lower survival rates were found in extraocular presentation (81.0%) versus intraocular tumors (P = 0.014), first enucleation after 1 month following diagnosis (80.9%) versus earlier first enucleation (P = 0.020), and relapse (100.0%) versus absence of relapse (P = 0.0005). CONCLUSIONS: Fifteen substitutions (4 intronic and 11 exonic) were identified as probably or likely pathogenic. Four of these 11 exonic substitutions were novel. Survival rates, however, were not affected by presence of these probably or likely pathogenic alterations, most of which not found in patients with retinoblastoma from other Latin American countries. These differences might be related to the different ethnic composition of the Latin American cohorts. Portuguese Abstract.