Etiology of hepatocellular carcinoma in West Africa, a case-control study.

Hepatocellular carcinoma (HCC) is a leading cause of cancer in West Africa where HBV infection is endemic. However, limited information is available on other risk factors such as alcohol use, HCV and HIV infection. A case-control study was conducted in referral hospitals of Abidjan (Cote d'Ivoire), Bamako (Mali) and Lome (Togo). Cases were matched with controls on age, gender and participating site. The diagnosis of HCC relied on the combination of one or more space-occupying lesions suggestive of an HCC on a standardized abdominal ultrasound and an α-fetoprotein level ≥400 ng/ml. HIV, HBV and HCV serology were performed. Hazardous alcohol use was assessed using the AUDIT questionnaire. A conditional logistic regression model was used to measure odds ratio (OR) with their 95% confidence intervals (CI). A total of 160 cases and 320 controls were included. Cases were predominantly men (80.0%) with a median age of 47 years (IQR 38-57). Hazardous alcohol use (OR = 4.5 [CI 1.1-18.5]), HBV infection (OR = 62.5 [CI 20.5-190.7]) and HCV infection OR = 35.9 [CI 10.0-130.3]) were independently associated with HCC. Combining the effect of HBV infection and alcohol, HBV-infected hazardous drinkers had an OR = 149.8 (CI 13.5-1 667.0), HBV mono-infected had an OR = 57.4 (CI 18.8-175.3) (ref: HBV-negative). Aside the independent association of alcohol use and HBV and HCV infection with HCC, a synergic effect between alcohol use and HBV infection was identified. Timely screening and care of HBV infection and hazardous drinking might prevent a significant number of HCC in West Africa.

Cosmetics as endocrine disruptors: are they a health risk?

Exposure to chemicals from different sources in everyday life is widespread; one such source is the wide range of products listed under the title "cosmetics", including the different types of popular and widely-advertised sunscreens. Women are encouraged through advertising to buy into the myth of everlasting youth, and one of the most alarming consequences is in utero exposure to chemicals. The main route of exposure is the skin, but the main endpoint of exposure is endocrine disruption. This is due to many substances in cosmetics and sunscreens that have endocrine active properties which affect reproductive health but which also have other endpoints, such as cancer. Reducing the exposure to endocrine disruptors is framed not only in the context of the reduction of health risks, but is also significant against the background and rise of ethical consumerism, and the responsibility of the cosmetics industry in this respect. Although some plants show endocrine-disrupting activity, the use of well-selected natural products might reduce the use of synthetic chemicals. Instruments dealing with this problem include life-cycle analysis, eco-design, and green labels; in combination with the committed use of environmental management systems, they contribute to "corporate social responsibility".

Evaluation of the impact of a breast cancer awareness program in rural Ghana: a cross-sectional survey.

Community awareness is crucial to early detection of breast cancer in low- and middle-income countries. In Ghana 60% of the cases are detected at late stages. Breast Care International (BCI) is a Ghanaian non-governmental organization dedicated to raising breast cancer awareness. A cross-sectional survey was designed to assess the impact of BCI program on knowledge, attitudes and practices (KAP) toward breast cancer among women from rural communities of Ghana. A total of 232 women were interviewed in June 2011 in the Ashanti region; of these 131 participants were from a community that received the BCI program in August 2010 (intervention group) and 101 from another community that received the program post-survey (referent group). Data analysis was performed using Epi-Info version 3.5.3. Knowledge about breast cancer among participants who received the program was better than among those who did not. Only 53.5% of participants from the referent group knew that breast cancer usually appears as painless breast lump when compared to 82.3% from the intervention group. Participants who attended the program were significantly more likely to obtain higher knowledge scores (odds ratio (OR) = 2.10, 95% confidence interval (CI) = 1.14-3.86) and to state practicing breast self-examination (OR = 12.29, 95% CI = 5.31-28.48). The BCI program improved KAP toward breast cancer. Further research is warranted to provide stronger evidence that the program improves breast cancer early detection.

Cervical cancer prevention in reproductive health services: knowledge, attitudes and practices of midwives in Côte d'Ivoire, West Africa.

BACKGROUND: Cervical cancer is the most common cancer among women and the leading cause of cancer deaths in women in Côte d'Ivoire. Low resource countries can now prevent this cancer by using HPV vaccine and effective and affordable screening tests. However the implementation of these prevention strategies needs well-trained human resources. Part of the solution could come from midwives by integrating cervical cancer prevention into reproductive health services. The aim of this survey was to assess knowledge, attitudes and practices of midwives towards cervical cancer prevention in Abidjan, Côte d'Ivoire, and to find out factors associated with appropriate knowledge. METHODS: A cross-sectional survey was conducted among midwives in the urban district of Abidjan, using a self-administered questionnaire. Knowledge was assessed by two scores. Factors associated with appropriate knowledge were determined using a logistic regression analysis. Attitudes and practices were described and compare using the Chi2 test. RESULTS: A total of 592 midwives were enrolled, including 24.5% of final-year students. 55.7% of midwives had appropriate knowledge on cervical cancer, and 42.4% of them had appropriate knowledge on cervical cancer prevention strategies. Conferences, courses taken at school of midwifery and special training sessions on cervical cancer (OR = 4.9, 95% CI [1.9 to 12.6], p <0.01) were associated with good knowledge on the management of this disease. Among these midwives, 18.4% had already benefited from a screening test for themselves, 37.7% had already advised screening to patients and 8.4% were able to perform a visual inspection. 50.3% of midwives knew HPV vaccine as a preventive method; among them 70.8% usually recommended it to young girls. CONCLUSION: Despite sufficient knowledge about cervical cancer prevention, attitudes and practices of midwives should be improved by organizing capacity building activities. This would ensure the success of integration of cervical cancer prevention into reproductive health services in countries like Côte d'Ivoire.

Is mammographic density differentially associated with breast cancer according to receptor status? A meta-analysis.

Mammographic density (MD) is a strong marker of breast cancer risk, but it is debated whether the association holds, and is of a similar magnitude, for different subtypes of breast cancer defined by receptor status or gene expression profiles. A literature search conducted in June 2012 was used to identify all studies that had investigated the association of MD with subtype-specific breast cancer, independent of age. 7 cohort/case-control and 12 case-only studies were included, comprising a total of >24,000 breast cancer cases. Random effects meta-analysis models were used to combine relative risks (RR) of MD with subtype-specific breast cancer for case-control studies, and in case-only studies to combine relative risk ratios (RRR) of receptor positive versus negative breast tumors. In case-control/cohort studies, relative to women in the lowest density category, women in the highest density category had 3.1-fold (95 % confidence interval [CI] 2.2, 4.2) and 3.2-fold (1.7, 5.9) increased risk of estrogen receptor positive (ER+) and ER- breast cancer, respectively. In case-only analyses, RRRs of breast tumors being ER+ versus ER- were 1.13 (95 % CI 0.89, 1.42) for medium versus minimal MD. MD remained associated with screen-detected ER+ tumors, despite the expectation of this association to be attenuated due to masking bias and overdiagnoses of ER+ tumors. In eight contributing studies, the association of MD did not differ by HER2 status. This combined evidence strengthens the importance of MD as a strong marker of overall and of subtype-specific risk, and confirms its value in overall breast cancer risk assessment and monitoring for both research and clinical purposes.

Cervical cancer screening by visual inspection in Côte d'Ivoire, operational and clinical aspects according to HIV status.

BACKGROUND: Cervical cancer screening is not yet standard of care of women attending HIV care clinics in Africa and presents operational challenges that need to be addressed. METHODS: A cervical cancer screening program based on visual inspection methods was conducted in clinics providing antiretroviral treatment (ART) in Abidjan, Côte d'Ivoire. An itinerant team of midwives was in charge of proposing cervical cancer screening to all HIV-positive women enrolled in ART clinics as well as to HIV-negative women who were attending the Abidjan national blood donor clinic. Positively screened women were systematically referred to a colposcopic examination. A phone-based tracking procedure was implemented to reach positively screened women who did not attend the medical consultation. The association between HIV status and cervical cancer screening outcomes was estimated using a multivariate logistic model. RESULTS: The frequency of positive visual inspection was 9.0% (95% CI 8.0-10.0) in the 2,998 HIV-positive women and 3.9% (95% CI 2.7-5.1) in the 1,047 HIV-negative ones (p < 10-4). In multivariate analysis, HIV infection was associated with a higher risk of positive visual inspection [OR = 2.28 (95% CI 1.61-3.23)] as well as more extensive lesions involving the endocervical canal [OR = 2.42 (95% CI 1.15-5.08)]. The use of a phone-based tracking procedure enabled a significant reduction of women not attending medical consultation after initial positive screening from 36.5% to 19.8% (p < 10-4). CONCLUSION: The higher frequency of positive visual inspection among HIV-positive women supports the need to extend cervical cancer screening program to all HIV clinics in West Africa. Women loss to follow-up after being positively screened is a major concern in cervical screening programs but yet, partly amenable to a phone tracking procedure.

Factors influencing general practitioners in the referral of elderly cancer patients.

BACKGROUND: A number of studies have identified advanced age as a barrier to accessing specialised oncological care. Many factors can influence the care provided for elderly patients after a diagnosis of cancer has been established or is suspected. Only one European study has analysed the decision processes leading general practitioners (GPs) to refer elderly patients with cancer to oncologists. The objectives of the current study are to describe the factors that influence these decisions and to identify the particular factors and GP characteristics that are associated with systematic referral of these patients in South-West France. METHODS: This is a cross-sectional study on a representative sample of GPs in Aquitaine, South-West France. Questionnaire items were selected using a Delphi consensus approach and sent by post. Two logistic regression models were constructed to investigate GPs' decisions to refer these patients. RESULTS: The response rate obtained was 30%. Half of the general practitioners reported "always" referring their elderly cancer patients to oncologists. More than 75% reported being influenced by patient-related elements (patient and/or family wishes, comorbid factors, unsuitability of invasive investigations, physical and mental autonomy), by cancer-related elements (severity of symptoms, expected side-effects) and an organisational element (whether the general practitioner was used to collaborating with oncologists). Logistic regression analysis showed that cancer site and organisational difficulties in patient management were significantly associated with the decision to refer elderly patients with early-stage cancer. For advanced stages, oncology training, patient age, organisational difficulties in patient management and stage of cancer were significantly associated with the decision to refer elderly patients. CONCLUSIONS: Cancer-linked factors and organisational difficulties have been highlighted as influencing the decisions of GPs in the referral of elderly patients to a cancer team. These results highlight the need to implement continuous medical education specific for the management of elderly patients, to better apprehend the nature of these difficulties and to suggest solutions suited to local settings.

Separate and combined analysis of successive dependent outcomes after breast-conservation surgery: recurrence, metastases, second cancer and death.

BACKGROUND: In the setting of recurrent events, research studies commonly count only the first occurrence of an outcome in a subject. However this approach does not correctly reflect the natural history of the disease. The objective is to jointly identify prognostic factors associated with locoregional recurrences (LRR), contralateral breast cancer, distant metastases (DM), other primary cancer than breast and breast cancer death and to evaluate the correlation between these events. METHODS: Patients (n = 919) with a primary invasive breast cancer and treated in a cancer center in South-Western France with breast-conserving surgery from 1990 to 1994 and followed up to January 2006 were included. Several types of non-independent events could be observed for the same patient: a LRR, a contralateral breast cancer, DM, other primary cancer than breast and breast cancer death. Data were analyzed separately and together using a random-effects survival model. RESULTS: LRR represent the most frequent type of first failure (14.6%). The risk of any event is higher for young women (less than 40 years old) and in the first 10 years of follow-up after the surgery. In the combined analysis histological tumor size, grade, number of positive nodes, progesterone receptor status and treatment combination are prognostic factors of any event. The results show a significant dependence between these events with a successively increasing risk of a new event after the first and second event. The risk of developing a new failure is greatly increased (RR = 4.25; 95%CI: 2.51-7.21) after developing a LRR, but also after developing DM (RR = 3.94; 95%CI: 2.23-6.96) as compared to patients who did not develop a first event. CONCLUSION: We illustrated that the random effects survival model is a more satisfactory method to evaluate the natural history of a disease with multiple type of events.

Carbon dioxide is largely responsible for the acute inflammatory effects of tobacco smoke.

Tobacco smoking is responsible for a vast array of diseases, particularly chronic bronchitis and lung cancer. It is still unclear which constituent(s) of the smoke is responsible for its toxicity. The authors decided to focus on carbon dioxide, since its level of concentration in mainstream cigarette smoke is about 200 times higher than in the atmosphere. The authors previously demonstrated that inhalation of carbon dioxide concentrations above 5% has a deleterious effect on lungs. In this study, the authors assessed the inflammatory potential of carbon dioxide contained in cigarette smoke. Mice were exposed to cigarette smoke containing a high or reduced CO(2) level by filtration through a potassium hydroxyde solution. The inflammatory response was evaluated by histological analysis, protein phosphatase 2 A (PP2A) and nuclear factor (NF)-kappaB activation, and proinflammatory cytokine secretion measurements. The data show that the toxicity of cigarette smoke may be largely due to its high level of CO(2). Pulmonary injuries consequent to tobacco smoke inhalation observed by histology were greatly diminished when CO(2) was removed. Cigarette smoke exposure causes an inflammatory response characterized by PP2A and NF-kappaB activation followed by proinflammatory cytokine secretion. This inflammatory response was reduced when the cigarette smoke was filtered through a potassium hydroxide column, and reestablished when CO(2) was injected downstream from the filtration column.Given that there is an extensive literature linking a chronic inflammatory response to the major smoking-related diseases, these data suggest that carbon dioxide may play a key role in the causation of these diseases by tobacco smoking.

Role of uncontrolled HIV RNA level and immunodeficiency in the occurrence of malignancy in HIV-infected patients during the combination antiretroviral therapy era: Agence Nationale de Recherche sur le Sida (ANRS) CO3 Aquitaine Cohort.

BACKGROUND: Human immunodeficiency virus (HIV)-infected patients are at higher risk of malignancies. In addition to traditional determinants, a specific deleterious effect of HIV and immunodeficiency is speculated. We aimed at studying the association between immunological and virological characteristics of HIV-infected patients in care and the risk of acquired immunodeficiency syndrome (AIDS)-defining and non-AIDS-defining malignancies. METHODS: Patients consecutively enrolled in the hospital-based Agence Nationale de Recherche sur le Sida (ANRS) CO3 Aquitaine Cohort were included if the duration of follow-up was >3 months during the period 1998-2006. Multivariate modeling used an extended Cox proportional hazards model for time-dependent covariates and delayed entry. RESULTS: The 4194 patients included in the study developed 251 first malignancies during 22,389 person-years. A higher incidence of AIDS-defining malignancies (107 cases) was independently associated with (1) both longer and current exposures to a plasma HIV RNA level >500 copies/mL (hazard ratio [HR], 1.27 per year [P<.001] and 3.30 [P<.001], respectively) and (2) both longer and current exposure to a CD4(+) cell count <200 cells/mm(3) (HR, 1.36 per year [P<.001] and 6.33 [P<.001], respectively). A higher incidence of non-AIDS-defining malignancies (144 cases) was independently associated with longer and current exposure to a CD4(+) cell count <500 cells/mm(3) (HR, 1.13 per year [P=.01] and 2.07 [P<.001], respectively) and male sex (HR, 1.69; P=.02) but not with plasma HIV RNA level (P=.49 and P=.10 for cumulative and current exposures, respectively). CONCLUSIONS: Uncontrolled plasma HIV RNA level was independently associated with a higher likelihood of developing AIDS-defining malignancies, whereas immunosuppression was associated with a higher risk of developing any type of malignancies. Antiretroviral treatment should aim at reaching and maintaining a CD4(+) count >500 cells/mm(3) to prevent the occurrence of malignancy, this should be integrated to malignancy-prevention policies.

Tobacco smoking and chewing as risk factors for multiple human papillomavirus infections and cervical squamous intraepithelial lesions in two countries (Côte d'Ivoire and Finland) with different tobacco exposure.

Our objective was to compare the association between tobacco smoking and chewing and the risk of multiple human papillomavirus (HPV) infections and cervical squamous intraepithelial lesions (SILs) in two populations with different tobacco exposure. We studied 2,162 women from Côte d'Ivoire, West Africa, and 419 women from Finland, Northern Europe, with baseline data on cervical screening, HPV DNA status and smoking and chewing habits. The proportion of women who smoked and/or chewed tobacco was higher in Finland (36.8%) than in Côte d'Ivoire (3.7%), where tobacco chewing (2.6%) was more common than tobacco smoking (1.4%). Having multiple HPV infections was common in HPV16 and/or 18-infected women (60.4% in Finland and 47.2% in Côte d'Ivoire). There was no increased risk of multiple HPV infections among tobacco consumers. We found that women >or=30 years of age exposed to tobacco through smoking in Finland (OR: 2.2, 95% CI: 0.5-8.7) and chewing in Côte d'Ivoire (OR: 5.5, 95% CI: 2.1-14) had a moderately or highly increased risk of high-grade SIL, respectively. In the latter, the risk was statistically significant. Our findings emphasize the need for health initiatives targeted to prevent tobacco smoking or chewing among women especially in less industrialized countries.

A lower risk of dying from urological cancer in Down syndrome: clue for cancer protecting genes on chromosome 21.

OBJECTIVE: It was the aim of this study to evaluate the risk of dying from bladder and kidney cancer in persons with Down syndrome (DS), as compared with the general population. METHODS: Using data of the French national mortality statistics (INSERM) during a 21-year period, 1979-1999, we compared the observed number of deaths from renal and bladder cancer in DS subjects with the expected number of deaths from these cancers. The expected number of deaths was calculated taking into account the prevalence of DS at birth and the life expectancy of persons with DS, assuming the risk was identical to the one of the general population. RESULTS: A significant 6-fold decreased risk of dying from urological cancer was found in persons with DS, with 5 cases observed, while 30 were expected. The relative risk of dying was 0.27 for bladder cancer (p = 0.0017) and 0.06 for kidney cancer (p < 0.0001). Other mortality studies provided similar values. CONCLUSIONS: Children and adults with DS have a decreased risk of dying from urological neoplasms. Genes on chromosome 21 could play a protective role against urological cancer.

Cancer prevention and population-based screening.

Cancer prevention, screening and early detection can provide some of the greatest public health benefits for cancer control. In low resource settings, where cancer control is challenged by limited human, financial and technical resources, cancer prevention and screening are of utmost importance and can provide significant impacts on the cancer burden. Public policies, social, environmental and individual level interventions which promote and support healthy eating and physical activity can lower cancer risks. Tobacco use, a significant cancer risk factor, can be reduced through the application of key mandates of the World Health Organization Framework Convention on Tobacco Control. In addition, cancer screening programs, namely for cervical and breast cancers, can have a significant impact on reducing cancer mortality, including in low resource settings. Comprehensive cancer control programs require interventions for cancer prevention, screening and early detection, and involve sectors outside of health to create supportive environments for healthy ways of life. Sharing experiences in implementing cancer control programs in different settings can create opportunities for interchanging ideas and forming international alliances.

Aberrant DNA methylation of P16, MGMT, and hMLH1 genes in combination with MTHFR C677T genetic polymorphism in esophageal squamous cell carcinoma.

To explore the role of aberrant hypermethylation of cancer-related genes, such as P16, MGMT, and hMLH1, in the esophageal squamous cell carcinoma (ESCC) as well as its relation to dietary folate intake and MTHFR C677T polymorphism, we conducted a molecular epidemiologic study in China. One hundred and twenty-five histologically confirmed ESCC patients having undergone surgery in the Yangzhong People's Hospital between January 2005 and March 2006 were recruited. The aberrant CpG island hypermethylation of P16, MGMT, and hMLH1 genes could be found in cancer tissues with frequency of about 88.0%, 27.2%, and 3.2%, respectively, and in remote normal-appearing esophageal tissues with frequency of about 36.8%, 11.2%, and 0.0%, respectively. No hypermethylation was found in the normal esophageal tissues from healthy controls. Compared with those patients without lymph node metastasis, MGMT gene showed a higher proportion of hypermethylation in cancer tissues, whereas P16 gene showed a higher proportion of hypermethylation in remote normal-appearing esophageal tissues in patients with lymph node metastasis. A significant association was found between MTHFR C677T genetic polymorphism and CpG island methylation status of MGMT gene. After adjustment for potential confounders, individuals carrying CT or TT genotype have higher frequency of hypermethylation in MGMT gene in cancer tissues, with odds ratio of 3.34 (95% confidence interval, 1.07-10.39) and 3.83 (95% confidence interval, 1.13-12.94), respectively. This study indicated that the aberrant CpG island hypermethylation of cancer-related genes was associated with ESCC and might be a promising biomarker in diagnosis and prognosis.

Cancer and globalization.

Global human cancer is increasing. Exposures to cancer risk factors are not only becoming more prevalent in the less industrialized countries, but they have also become more complex all over the world. Human societies have always traded and migrated, yet the growth of powerful economic institutions and globalization is accelerating, mixing many cancer risk factors. Critically, new cancer risk factors have also appeared, concurrent with globalization: modern diet, addictive products, pharmaceuticals, and toxic and waste products. Prevention, which still rests on recognition and elimination of exposure to carcinogens, is difficult, with seemingly opposed priorities such as income (corporate or individual) versus health. The solutions require not only individual behavioural change but also more importantly innovative action of all concerned at the global, collective level.

Sex ratio changes as sentinel health events of endocrine disruption.

The production and widespread use of synthetic chemicals since the 1940s have resulted in ubiquitous contamination of fish, wildlife and human populations. Since the 1960s, observers have documented major damage to wildlife reproduction across the globe, and subsequently, damage to reproductive health in exposed humans as well. The sex ratio in human communities and populations can be readily measured to ascertain whether reproductive effects, such as subtle birth defects of the reproductive tract caused by exposures to chemicals, might be occurring. Male to female sex ratios appear to be declining in populations in several parts of the globe, possibly as a result of prenatal exposures to chemicals. Sex ratio data for communities with unusual occupational or environmental exposures can be compiled using traditional epidemiological techniques in pursuit of environmental justice. Local, regional and national population health researchers and occupational hygienists can use health statistics to examine sex ratios as sentinel health events that might portend patterns of subtle structural birth defects of the reproductive tract and functional deficits in neurodevelopment.

Lung cancer risk and workplace exposure to environmental tobacco smoke.

OBJECTIVES: We sought to quantitatively evaluate the association between work-place environmental tobacco smoke exposure and lung cancer. METHODS: We performed a meta-analysis in 2003 of data from 22 studies from multiple locations worldwide of workplace environmental tobacco smoke exposure and lung cancer risk. Estimates of relative risk from these studies were analyzed by fitting the data to fixed and mixed effects models. Analyses of highly exposed workers and of the relationship between duration of exposure and lung cancer were also performed. RESULTS: The meta-analysis indicated a 24% increase in lung cancer risk (relative risk [RR]=1.24; 95% confidence interval [CI]=1.18, 1.29) among workers exposed to environmental tobacco smoke. A 2-fold increased risk (RR=2.01; 95% CI=1.33, 2.60) was observed for workers classified as being highly exposed to environmental tobacco smoke. A strong relationship was observed between lung cancer and duration of exposure to environmental tobacco smoke. CONCLUSIONS: The findings from this investigation provide the strongest evidence to date that exposure to environmental tobacco smoke in the workplace is associated with an increased risk of lung cancer.

The need to develop centers for environmental oncology.

The scale and scope of the cancer problem in the United States today is much greater than four decades ago when the formal war against the disease was first announced. Patterns of the disease are not fully explained by known risk factors. Much progress has been made in understanding the molecular basis of carcinogenesis, particularly the near consensus (realization) that virtually all cancers arise from an accumulation of genetic mutations and the more recent recognition of the role of inflammation and the tissue microenvironment, in particular for hormone-dependent cancers. However, most genetic mutations that contribute to cancer are not inherited, and thus must be attributable to accumulation of somatic mutations and epigenetic changes, from as yet poorly understood environmental factors, that certainly cannot be explained entirely by tobacco, use and arise over the course of a lifetime. Much of the national effort to control cancer has focused on detecting and treating the disease--not on seeking approaches to prevent cases from arising. Given this reality, we present a cross-disciplinary framework for establishing comprehensive research and policy centers focused on environmental oncology to be based at selected academic cancer centers across the country. The principal goal of such centers is to improve the ability to prevent cancer, by developing effective interventions based on insights obtained from epidemiology, including molecular epidemiology and basic scientific research on genomic, metabolomic, and other biomarkers of exposure, susceptibility, and disease. As the needed scientific evidence for environmental factors contributing to cancer is revealed, these academic centers will develop specific interventions and/or policy recommendations regarding ways to lower the burden of cancer, based on existing information about cancer hazards in the personal, occupational, and general environment. Ultimately the centers will improve the ability to identify and control the underlying causes of the occurrence of cancer and its progression.

Personal care products that contain estrogens or xenoestrogens may increase breast cancer risk.

Established models of breast cancer risk, such as the Gail model, do not account for patterns of the disease in women under the age of 35, especially in African Americans. With the possible exceptions of ionizing radiation or inheriting a known genetic mutation, most of the known risk factors for breast cancer are related to cumulative lifetime exposure to estrogens. Increased risk of breast cancer has been associated with earlier onset of menses or later age at menopause, nulliparity or late first parity, use of hormonal contraceptives or hormone replacement therapy, shorter lactation history, exposure to light at night, obesity, and regular ingestion of alcohol, all of which increase circulating levels of unbound estradiol. Among African Americans at all ages, use of hormone-containing personal care products (PCPs) is more common than among whites, as is premature appearance of secondary sexual characteristics among infants and toddlers. We hypothesize that the use of estrogen and other hormone-containing PCPs in young African American women accounts, in part, for their increased risk of breast cancer prior to menopause, by subjecting breast buds to elevated estrogen exposure during critical windows of vulnerability in utero and in early life. These early life and continuing exposures to estrogenic and xenoestrogenic agents may also contribute to the increased lethality of breast cancer in young women in general and in African American women of all ages. Public disclosure by manufacturers of proprietary hormonally active ingredients is required for this research to move forward.

Breast cancer risk among women who start smoking as teenagers.

OBJECTIVE: To examine the effect of smoking on breast cancer risk in a large population-based cohort of women, many of whom started smoking as teenagers. METHODS: We followed 102,098 women, ages 30 to 50 years, completing a mailed questionnaire at recruitment to the Norwegian-Swedish Cohort Study in 1991/1992, through December 2000. We used Cox proportional hazard regression models to estimate relative risk (RR) of breast cancer associated with different measures of smoking initiation, duration, and intensity adjusting for confounding variables. We conducted analyses on the entire study population, among women who had smoked for at least 20 years, among nondrinkers, and separately for each country. RESULTS: Altogether, 1,240 women were diagnosed with incident, invasive breast cancer. Compared with never smokers, women who smoked for at least 20 years and who smoked 10 cigarettes or more daily had a RR of 1.34 (95% CI, 1.06-1.70). Likewise, those who initiated smoking prior to their first birth (1.27, 1.00-1.62), before menarche (1.39, 1.03-1.87), or before age 15 (1.48, 1.03-2.13) had an increased risk. In contrast, women who had smoked for at least 20 years, but started after their first birth, did not experience an increased breast cancer risk. The increased RR associated with smoking was observed among nondrinkers of alcohol, women with and without a family history of breast cancer, premenopausal and postmenopausal women, and in both countries. CONCLUSION: Our results support the notion that women who start smoking as teenagers and continue to smoke for at least 20 years may increase their breast cancer risk.