Paule Latino-Martel

Beta-carotene supplementation and cancer risk: a systematic review and metaanalysis of randomized controlled trials

The effect of beta‐carotene supplementation on cancer incidence has been investigated in several randomized controlled trials. The objective was to review the effect of beta‐carotene supplementation on cancer incidence in randomized trials by cancer site, beta‐carotene supplementation characteristics and study population. Relevant trials were retrieved by searching PubMed (up to April 2009). Authors involved in selected studies were contacted for additional information. Thirteen publications reporting results from 9 randomized controlled trials were included. Overall, no effect of beta‐carotene supplementation was observed on the incidence of all cancers combined (RR, 1.01; 95% CI, 0.98–1.04), pancreatic cancer (RR, 0.99; 95% CI, 0.73–1.36), colorectal cancer (RR, 0.96; 95% CI, 0.85–1.09), prostate cancer (RR, 0.99; 95% CI, 0.91–1.07), breast cancer (RR, 0.96; 95% CI, 0.85–1.10), melanoma (RR, 0.98; 95% CI, 0.65–1.46) and non melanoma skin cancer (RR, 0.99; 95% CI, 0.93–1.05). The incidence of lung and stomach cancers were significantly increased in individuals supplemented with beta‐carotene at 20–30 mg day−1 (RR, 1.16; 95% CI, 1.06–1.27 and RR, 1.34; 95% CI, 1.06–1.70), in smokers and asbestos workers (RR, 1.20; 95% CI, 1.07–1.34 and RR, 1.54; 95% CI, 1.08–2.19) compared to the placebo group. Beta‐carotene supplementation has not been shown to have any beneficial effect on cancer prevention. Conversely, it was associated with increased risk not only of lung cancer but also of gastric cancer at doses of 20–30 mg day−1, in smokers and asbestos workers. This study adds to the evidence that nutritional prevention of cancer through beta‐carotene supplementation should not be recommended.

Alcohol and genetic polymorphisms: effect on risk of alcohol-related cancer

Public health guidelines aim to limit the consumption of alcoholic beverages worldwide and the subsequent health burden. In particular, alcohol consumption is an avoidable risk factor for cancer. In human beings, ethanol in alcoholic drinks is mainly oxidised in the liver by alcohol dehydrogenases to acetaldehyde, and is further detoxified to acetate by aldehyde dehydrogenases. Functional variants in genes involved in alcohol metabolism result in differences between individuals in exposure to carcinogenic acetaldehyde, suggesting a possible interaction of genetic susceptibility and alcohol exposure in cancer. We reviewed available studies of the combined effects of alcohol drinking and genetic polymorphisms on alcohol-related cancer risk. Most available data were for polymorphisms in alcohol and folate metabolism. We give an overview of published studies on the combined effects of alcohol drinking and polymorphisms in genes for alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), cytochrome P450 2E1, and methylene-tetrahydrofolate reductase on the risk of alcohol-related cancer. Current data lend support to a role of polymorphisms ADH1B and ALDH2 combined with alcohol consumption in cancer. Other available data are insufficient or inconclusive, highlighting the need for additional studies.

Maternal Alcohol Consumption during Pregnancy and Risk of Childhood Leukemia: Systematic Review and Meta-analysis

Background: Leukemia is the most frequently occurring cancer in children. Although its etiology is largely unknown, leukemia is believed to result from an interaction between genetic and environmental factors. Among different potential risk factors, the possible role of maternal alcohol consumption during pregnancy has been questioned. Methods: To assess the association between maternal alcohol consumption during pregnancy and childhood leukemia, a systematic review and meta-analysis of published studies was done. Results: Twenty-one case-control studies were included in categorical and dose-response meta-analyses. No cohort study was identified. Analyses were conducted by type of leukemia, childrens age at diagnosis, and type of alcoholic beverage and trimester of pregnancy at alcohol use. Alcohol intake during pregnancy (yes versus no) was statistically significantly associated with childhood acute myeloid leukemia (AML) [odds ratio (OR), 1.56; 95% confidence interval (CI), 1.13-2.15] but not with acute lymphoblastic leukemia (OR, 1.10; 95% CI, 0.93-1.29). Heterogeneity between studies was observed. The OR of AML for an increase of a drink per week was 1.24 (95% CI, 0.94-1.64). The association of alcohol intake during pregnancy with AML was observed for cancers diagnosed at age 0 to 4 years (OR, 2.68; 95% CI, 1.85-3.89) in five studies without heterogeneity (I2 ≤ 0.1%). Conclusions: The results of case-control studies indicate that maternal alcohol consumption during pregnancy is associated with a significantly increased risk of AML in young children. Impact: Avoidance of maternal alcohol drinking during pregnancy might contribute to a decrease in the risk of childhood AML. Cancer Epidemiol Biomarkers Prev; 19(5); 1238–60. ©2010 AACR.

Incidence of cancers, ischemic cardiovascular diseases and mortality during 5‐year follow‐up after stopping antioxidant vitamins and minerals supplements: A postintervention follow‐up in the SU.VI.MAX Study

The Supplementation in Vitamins and Mineral Antioxidants Study was a double‐blind, placebo‐controlled, randomized trial, in which 12,741 French adults (7,713 women aged 35–60 years and 5,028 men aged 45–60 years) received a combination of ascorbic acid (120 mg), vitamin E (30 mg), β‐carotene (6 mg), selenium (100 μg) and zinc (20 mg), or placebo daily for a median follow‐up time of 7.5 years [October 1994 to September 2002]. Antioxidant supplementation decreased total cancer incidence and total mortality in men. Postintervention follow‐up assessment of total cancer incidence, ischemic cardiovascular disease incidence and total mortality was carried out for 5 years [September 1, 2002, to September 1, 2007]. No late effect of antioxidant supplementation was revealed 5 years after ending the intervention neither on ischemic cardiovascular disease incidence and mortality in both genders nor on cancer incidence in women. Regarding duration of intervention effects in men, the reduced risk of total cancer incidence and total mortality was no longer evident after the 5‐year postintervention follow‐up. During the postsupplementation period, the relative risk (RR) for total cancer incidence (n = 126) was 0.98 (95% confidence interval [CI], 0.75–1.27) among antioxidant recipients compared to nonrecipients. For total mortality (n = 90), the RR was 0.98 (95% CI, 0.75–1.26) for men receiving antioxidants compared to nonrecipients. In conclusion, beneficial effects of antioxidant supplementation in men disappeared during postintervention follow‐up.

Socioeconomic differences in fruit and vegetable consumption among middle-aged French adults: adherence to the 5 A Day recommendation.

BACKGROUND Numerous studies support the protective effect of high fruit and vegetable consumption on chronic disease risk, mainly against cancer and cardiovascular diseases. The increase of fruit and vegetable intake has become a public health priority in many countries. OBJECTIVE The aim of the study was to investigate the relationships of socioeconomic, demographic, and behavioral factors with both quantity and variety of fruit and vegetable consumption. DESIGN/SUBJECTS Fruit and vegetable intake was assessed using repeated 24-hour dietary records collected during a 2-year period from 4,282 French subjects (2,373 men and 1,909 women), aged 45 to 62 years, who participated in a large prospective study. STATISTICAL ANALYSIS Both education level and occupation categories were used as socioeconomic indicators. Logistic regression models were applied to assess factors related to meeting the 5 A Day fruit and vegetable recommendation. Covariance analyses were performed to compare the fruit and vegetable variety scores and the contributions of fruit and vegetables to the total daily diet cost across socioeconomic indicators within each sex. RESULTS Meeting the 5 A Day recommendation was more likely in subjects aged 50 years and older, higher education levels, nonsmokers, moderate alcohol drinkers and in women engaging in regular physical activity. The odds ratio (95% confidence interval) for the lower vs higher education level was 0.70 (0.54 to 0.92) in men and 0.65 (0.48 to 0.85) in women. No significant difference was observed between occupation categories. A positive relationship between vegetable variety and education level was found in both sexes. Fruit variety was positively associated with both education and occupation categories, but only in men. The contribution of fruits to the total daily diet cost increased with occupation (P<0.02) and education (P<0.0001) in men, but decreased with occupation in women (P<0.05). CONCLUSIONS Although cost constraints may explain the lower fruit and vegetable intake in lower socioeconomic groups, the relative influence of budgetary resources, nutrition knowledge, and social and environmental barriers in socioeconomic disparities need further investigation.

Determinants of vitamin D status in Caucasian adults: influence of sun exposure, dietary intake, sociodemographic, lifestyle, anthropometric, and genetic factors.

Very few studies have investigated the determinants of serum vitamin D levels using a set of variables that include simultaneously sun exposure, phototype, dietary intake, sociodemographics, anthropometric, lifestyle data, and genetic polymorphisms. Our objective was to investigate the associations between all these parameters and vitamin D status in a large sample of French adults. This cross-sectional survey was based on 1,828 middle-aged Caucasian adults from the SU.VI.MAX (SUpplémentation en VItamines et Minéraux AntioXydants) study. Plasma 25-hydroxyvitamin D (25OHD) concentration was lower among women (P<0.0001), older subjects (P=0.04), obese/underweight (P<0.0001), those living at higher latitudes (P<0.0001), those whose blood draw occurred in early spring (P<0.0001), less physically active (P<0.0001), with low sun exposure (P<0.0001), and with no-to-low alcohol intake (P=0.0001). Mutant GC rs4588 and rs7041 single nucleotide polymorphisms were associated with lower and higher 25OHD concentrations, respectively (P<0.0001). Dietary intake was not a major determinant of vitamin D status (P=0.7). This study provides an overall picture of determinants of vitamin D status. Several modifiable factors were identified, such as daily-life moderate sun exposure, physical activity, and normal-weight maintenance, which should be targeted by public health policies in order to improve vitamin D status in the general population, while avoiding active/intensive sun exposure, in line with recommendations for skin cancer prevention.

Alcoholic beverages, obesity, physical activity and other nutritional factors, and cancer risk: A review of the evidence

PURPOSE Prevention is a priority in the fight against cancers, especially nutritional prevention. To update the levels of evidence of relationships between 10 nutritional factors and cancer risk, the scientific literature published from 2006 to 2014 was reviewed by an expert group. METHODS Data from 133 meta-analyses, pooled analyses or intervention trials were examined. Nearly 150 relationships between nutritional factors and cancer at various sites were evaluated. RESULTS According to the evidence graded as convincing or probable, these factors were divided in two groups. Factors which increase the risk of cancer are alcoholic beverages, overweight and obesity, red meat and processed meat, salt and salted foods and beta-carotene supplements. Factors which decrease the risk of cancer are physical activity, fruits and vegetables, dietary fiber, dairy products and breastfeeding. CONCLUSION Three main nutritional objectives should be attained to improve cancer prevention: to reduce alcoholic beverages consumption, to have a balanced and diversified diet and to be physically active.

Interpretation of Plasma PTH Concentrations According to 25OHD Status, Gender, Age, Weight Status, and Calcium Intake: Importance of the Reference Values

CONTEXT Reference values for plasma PTH assessment were generally established on small samples of apparently healthy subjects, without considering their 25-hydroxyvitamin D (25OHD) status or other potential modifiers of PTH concentration. OBJECTIVE Our objective was to assess ranges of plasma PTH concentration in a large sample of adults, stratifying by 25OHD status, age, gender, weight status, and calcium intake. DESIGN, SETTING, AND PARTICIPANTS This cross-sectional survey is based on 1824 middle-aged Caucasian adults from the Supplémentation en Vitamines et Minéraux Antioxydants study (1994). MAIN OUTCOME MEASURES Plasma PTH and 25OHD concentrations were measured by an electrochemoluminescent immunoassay. Extreme percentiles of plasma PTH concentrations were assessed specifically in subjects who had plasmatic values of 25OHD of 20 ng/mL or greater and 30 ng/mL or greater. RESULTS Among subjects with 25OHD status of 20 ng/mL or greater, the 97.5th percentile of plasma PTH concentration was 45.5 ng/L. By using this value as a reference, 5% of the subjects with plasma 25OHD less than 20 nmol/L had a high plasma PTH level, reflecting secondary hyperparathyroidism. Among vitamin D-replete subjects (25OHD status of 20 ng/mL or greater), the 97.5th percentile of plasma PTH was higher in overweight/obese subjects (51.9 vs 43.5 ng/L among normal weight subjects). CONCLUSIONS The reference value for plasma PTH defined in this vitamin D-replete population was far below the value currently provided by the manufacturer (65 ng/L) and varied according to overweight status. These results may contribute to improve the diagnosis of primary and secondary hyperparathyroidism and subsequent therapeutic indication.

Dietary Total and Insoluble Fiber Intakes Are Inversely Associated with Prostate Cancer Risk

Although experimental data suggest a potentially protective involvement of dietary fiber in prostate carcinogenesis, very few prospective studies have investigated the relation between dietary fiber intake and prostate cancer risk, and those have had inconsistent results. Our objective was to study the association between dietary fiber intake (overall, insoluble, soluble, and from different sources, such as cereals, vegetables, fruits, and legumes) and prostate cancer risk. Stratifications by excess weight status, insulin-like growth factors, and amount of alcohol intake were also considered. This prospective analysis included 3313 men from the Supplémentation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) cohort who completed at least 3 24-h dietary records. One hundred thirty-nine incident prostate cancers were diagnosed between 1994 and 2007 (median follow-up of 12.6 y). Associations between quartiles of energy-adjusted dietary fiber intake and prostate cancer risk were characterized by multivariate Cox proportional hazards models. Prostate cancer risk was inversely associated with total dietary fiber intake (HR of quartile 4 vs. quartile 1 = 0.47; 95% CI: 0.27, 0.81; P = 0.001), insoluble (HR = 0.46; 95% CI: 0.27, 0.78; P = 0.001), and legume (HR = 0.55; 95% CI: 0.32, 0.95; P = 0.04) fiber intakes. In contrast, we found no association between prostate cancer risk and soluble (P = 0.1), cereal (P = 0.7), vegetable (P = 0.9), and fruit (P = 0.4) fiber intakes. In conclusion, dietary fiber intake (total, insoluble, and from legumes but not soluble or from cereals, vegetables, and fruits) was inversely associated with prostate cancer risk, consistent with mechanistic data.

Alcohol Drinking and Second Primary Cancer Risk in Patients with Upper Aerodigestive Tract Cancers: A Systematic Review and Meta-analysis of Observational Studies

Background: We conducted a systematic review and meta-analysis of existing data from observational studies to assess the strength of the association of alcohol drinking with second primary cancer risk in patients with upper aerodigestive tract (UADT; oral cavity, pharynx, larynx, and esophagus) cancer. Methods: PubMed and Embase were searched up to July 2012 and the reference lists of studies included in the analysis were examined. Random-effects models were used to estimate summary relative risks (RR) and 95% confidence interval (CI). Results: Nineteen studies, 8 cohort and 11 case–control studies, were included. In highest versus lowest meta-analyses, alcohol drinking was associated with significantly increased risk of UADT second primary cancers (RR, 2.97; 95% CI, 1.96–4.50). Significantly increased risks were also observed for UADT and lung combined (RR, 1.90; 95% CI, 1.16–3.11) and all sites (RR, 1.60; 95% CI, 1.22–2.10) second primary cancers. For an increase in the alcohol intake of 10 grams per day, dose–response meta-analysis resulted in a significantly increased RR of 1.09 (95% CI, 1.04–1.14) for UADT second primary cancers. Conclusions: Alcohol drinking in patients with UADT cancer is associated with an increased risk of second primary cancers. Studies conducted in alcohol drinking patients with UADT cancer and evaluating the effect of alcohol cessation on second primary cancer and other outcomes are needed. Impact: Our results emphasize the importance of prevention policies aiming to reduce alcohol drinking. Health-care professionals should encourage alcohol drinking patients with UADT cancer to reduce their consumption and reinforce the surveillance of this at-risk subpopulation. Cancer Epidemiol Biomarkers Prev; 23(2); 324–31. ©2013 AACR.