Mathieu Boniol

Vitamin D status and ill health: a systematic review

Low serum concentrations of 25-hydroxyvitamin D (25[OH]D) have been associated with many non-skeletal disorders. However, whether low 25(OH)D is the cause or result of ill health is not known. We did a systematic search of prospective and intervention studies that assessed the effect of 25(OH)D concentrations on non-skeletal health outcomes in individuals aged 18 years or older. We identified 290 prospective cohort studies (279 on disease occurrence or mortality, and 11 on cancer characteristics or survival), and 172 randomised trials of major health outcomes and of physiological parameters related to disease risk or inflammatory status. Investigators of most prospective studies reported moderate to strong inverse associations between 25(OH)D concentrations and cardiovascular diseases, serum lipid concentrations, inflammation, glucose metabolism disorders, weight gain, infectious diseases, multiple sclerosis, mood disorders, declining cognitive function, impaired physical functioning, and all-cause mortality. High 25(OH)D concentrations were not associated with a lower risk of cancer, except colorectal cancer. Results from intervention studies did not show an effect of vitamin D supplementation on disease occurrence, including colorectal cancer. In 34 intervention studies including 2805 individuals with mean 25(OH)D concentration lower than 50 nmol/L at baseline supplementation with 50 μg per day or more did not show better results. Supplementation in elderly people (mainly women) with 20 μg vitamin D per day seemed to slightly reduce all-cause mortality. The discrepancy between observational and intervention studies suggests that low 25(OH)D is a marker of ill health. Inflammatory processes involved in disease occurrence and clinical course would reduce 25(OH)D, which would explain why low vitamin D status is reported in a wide range of disorders. In elderly people, restoration of vitamin D deficits due to ageing and lifestyle changes induced by ill health could explain why low-dose supplementation leads to slight gains in survival.

Tobacco smoking and cancer: A meta-analysis

We conducted a systematic meta‐analysis of observational studies on cigarette smoking and cancer from 1961 to 2003. The aim was to quantify the risk for 13 cancer sites, recognized to be related to tobacco smoking by the International Agency for Research on Cancer (IARC), and to analyze the risk variation for each site in a systematic manner. We extracted data from 254 reports published between 1961 and 2003 (177 case‐control studies, 75 cohorts and 2 nested case‐control studies) included in the 2004 IARC Monograph on Tobacco Smoke and Involuntary Smoking. The analyses were carried out on 216 studies with reported estimates for ‘current’ and/or ‘former’ smokers. We performed sensitivity analysis, and looked for publication and other types of bias. Lung (RR = 8.96; 95% CI: 6.73–12.11), laryngeal (RR = 6.98; 95% CI: 3.14–15.52) and pharyngeal (RR = 6.76; 95% CI: 2.86–15.98) cancers presented the highest relative risks (RRs) for current smokers, followed by upper digestive tract (RR = 3.57; 95% CI: 2.63–4.84) and oral (RR = 3.43; 95% CI: 2.37–4.94) cancers. As expected, pooled RRs for respiratory cancers were greater than the pooled estimates for other sites. The analysis of heterogeneity showed that study type, gender and adjustment for confounding factors significantly influence the RRs estimates and the reliability of the studies.

Cutaneous melanoma attributable to sunbed use : systematic review and meta-analysis

Objective To estimate the burden of melanoma resulting from sunbed use in western Europe. Design Systematic review and meta-analysis. Data sources PubMed, ISI Web of Science (Science Citation Index Expanded), Embase, Pascal, Cochrane Library, LILACS, and MedCarib, along with published surveys reporting prevalence of sunbed use at national level in Europe. Study selection Observational studies reporting a measure of risk for skin cancer (cutaneous melanoma, squamous cell carcinoma, basal cell carcinoma) associated with ever use of sunbeds. Results Based on 27 studies ever use of sunbeds was associated with a summary relative risk of 1.20 (95% confidence interval 1.08 to 1.34). Publication bias was not evident. Restricting the analysis to cohorts and population based studies, the summary relative risk was 1.25 (1.09 to 1.43). Calculations for dose-response showed a 1.8% (95% confidence interval 0% to 3.8%) increase in risk of melanoma for each additional session of sunbed use per year. Based on 13 informative studies, first use of sunbeds before age 35 years was associated with a summary relative risk of 1.87 (1.41 to 2.48), with no indication of heterogeneity between studies. By using prevalence data from surveys and data from GLOBOCAN 2008, in 2008 in the 15 original member countries of the European Community plus three countries that were members of the European Free Trade Association, an estimated 3438 cases of melanoma could be attributable to sunbed use, most (n=2341) occurring among women. Conclusions Sunbed use is associated with a significant increase in risk of melanoma. This risk increases with number of sunbed sessions and with initial usage at a young age (<35 years). The cancerous damage associated with sunbed use is substantial and could be avoided by strict regulations.

Meta-analysis of observational studies of serum 25-hydroxyvitamin D levels and colorectal, breast and prostate cancer and colorectal adenoma.

Epidemiological studies have suggested a reduced risk of several cancers associated with high vitamin D status. We performed a systematic review with meta‐analyses of observational studies of serum 25‐hydroxyvitamin D level and colorectal, breast and prostate cancer and colonic adenoma. The literature of December 2009 was searched without language restriction. The meta‐regression analysis was done to compute dose‐response effects. Because in case‐control studies, serum 25‐hydroxyvitamin D level is measured after the diagnosis of cancer, separate analyses for case‐control and prospective studies were done. We identified 35 independent studies. The seven studies on colorectal adenomas were heterogeneous in terms of endpoint and control for major confounding factors, and we did not perform a meta‐analysis of these data. The summary relative risk (SRR) and (95% confidence interval) for a 10 ng/ml increase in serum 25‐hydroxyvitamin D was 0.85 (0.79; 0.91) for colorectal cancer (2,630 cases in 9 studies); 0.89 (0.81;0.98) for breast cancer (6,175 cases in 10 studies); and 0.99 (0.95;1.03) for prostate cancer (3,956 cases in 11 studies). For breast cancer, case‐control studies (3,030 cases) had major limitations and obtained SRR of 0.83 (0.79; 0.87) whereas SRR of prospective studies (3,145 cases) was 0.97 (0.92; 1.03). For colorectal and breast cancer, differences between cases and controls in the season of blood draw or in overweight/obesity or physical inactivity could not explain the results. In conclusion, a consistent inverse relationship between serum 25‐hydroxyvitamin D levels and colorectal cancer was found. No association was found for breast and prostate cancer.

Disparities in breast cancer mortality trends between 30 European countries: retrospective trend analysis of WHO mortality database

Objective To examine changes in temporal trends in breast cancer mortality in women living in 30 European countries. Design Retrospective trend analysis. Data source WHO mortality database on causes of deaths Subjects reviewed Female deaths from breast cancer from 1989 to 2006 Main outcome measures Changes in breast cancer mortality for all women and by age group (<50, 50-69, and ≥70 years) calculated from linear regressions of log transformed, age adjusted death rates. Joinpoint analysis was used to identify the year when trends in all age mortality began to change. Results From 1989 to 2006, there was a median reduction in breast cancer mortality of 19%, ranging from a 45% reduction in Iceland to a 17% increase in Romania. Breast cancer mortality decreased by ≥20% in 15 countries, and the reduction tended to be greater in countries with higher mortality in 1987-9. England and Wales, Northern Ireland, and Scotland had the second, third, and fourth largest decreases of 35%, 29%, and 30%, respectively. In France, Finland, and Sweden, mortality decreased by 11%, 12%, and 16%, respectively. In central European countries mortality did not decline or even increased during the period. Downward mortality trends usually started between 1988 and 1996, and the persistent reduction from 1999 to 2006 indicates that these trends may continue. The median changes in the age groups were −37% (range −76% to −14%) in women aged <50, −21% (−40% to 14%) in 50-69 year olds, and −2% (−42% to 80%) in ≥70 year olds. Conclusions Changes in breast cancer mortality after 1988 varied widely between European countries, and the UK is among the countries with the largest reductions. Women aged <50 years showed the greatest reductions in mortality, also in countries where screening at that age is uncommon. The increasing mortality in some central European countries reflects avoidable mortality.

Tyrol Prostate Cancer Demonstration Project: early detection, treatment, outcome, incidence and mortality

To evaluate the effectiveness of a well‐controlled programme of early detection and treatment of prostate cancer in the population of Tyrol, Austria, where such a programme of early detection and treatment was initiated in 1988 and where prostate‐specific antigen (PSA) testing was offered for free to all men aged 45–75 years from 1993.

Sunscreen use and increased duration of intentional sun exposure: Still a burning issue

Sunscreen use is often proposed for sun protection because of their ability to block UV‐induced sunburns (the sun protection factor – SPF). Among suntan seekers, however, risk of cutaneous melanoma may be increased because of extended sun exposure duration. We made a systematic review of the evidence linking sunscreen use to sun exposure duration. Five observational studies found that when sun exposure was associated with willingness to get a tan or to stay longer in the sun (i.e., intentional sun exposure), sunscreen use was associated with duration of sun exposure 13–39% longer. Paradoxically, sunburns tend to be more frequent among sunscreen users, probably because of greater natural sun sensitivity. When sun exposure was not intentional, sunscreen use did not increase time spent in the sun. Two European double‐blind randomized trials conducted among young sun seekers found daily sun exposure duration, especially sunbathing, 19–25% longer with use of SPF 30 than with use of SPF 10 sunscreens. One randomized trial in a holiday resort in France found a 3–13% increase in sun exposure duration with use of SPF 12 versus SPF 40 sunscreen. But, the SPF 12 groups used 3.6–4.2 more sunscreen than the SPF 40 group, and thus the actual SPF in the SPF 12 group was higher than in the SPF 40 groups. In conclusion, sunscreen use leads to longer duration of sun exposure when sun exposure is intentional, but not when sun exposure is non intentional.

Quantity of sunscreen used by European students.

Background The ability of sunscreen products to delay sun‐induced skin erythema is indicated by the sun protection factor (SPF), which is measured using an internationally agreed sunscreen thickness of 2 mg cm−2.

Estimates of the cancer burden in Europe from radioactive fallout from the Chernobyl accident

The Chernobyl accident, which occurred April 26, 1986, resulted in a large release of radionuclides, which were deposited over a very wide area, particularly in Europe. Although an increased risk of thyroid cancer in exposed children has been clearly demonstrated in the most contaminated regions, the impact of the accident on the risk of other cancers as well as elsewhere in Europe is less clear. The objective of the present study was to evaluate the human cancer burden in Europe as a whole from radioactive fallout from the accident. Average country‐ and region‐specific whole‐body and thyroid doses from Chernobyl were estimated using new dosimetric models and radiological data. Numbers of cancer cases and deaths possibly attributable to radiation from Chernobyl were estimated, applying state‐of‐the‐art risk models derived from studies of other irradiated populations. Simultaneously, trends in cancer incidence and mortality were examined over time and by dose level. The risk projections suggest that by now Chernobyl may have caused about 1,000 cases of thyroid cancer and 4,000 cases of other cancers in Europe, representing about 0.01% of all incident cancers since the accident. Models predict that by 2065 about 16,000 (95% UI 3,400–72,000) cases of thyroid cancer and 25,000 (95% UI 11,000–59,000) cases of other cancers may be expected due to radiation from the accident, whereas several hundred million cancer cases are expected from other causes. Although these estimates are subject to considerable uncertainty, they provide an indication of the order of magnitude of the possible impact of the Chernobyl accident. It is unlikely that the cancer burden from the largest radiological accident to date could be detected by monitoring national cancer statistics. Indeed, results of analyses of time trends in cancer incidence and mortality in Europe do not, at present, indicate any increase in cancer rates—other than of thyroid cancer in the most contaminated regions—that can be clearly attributed to radiation from the Chernobyl accident.

Advanced Breast Cancer and Breast Cancer Mortality in Randomized Controlled Trials on Mammography Screening

PURPOSE We assessed changes in advanced cancer incidence and cancer mortality in eight randomized trials of breast cancer screening. PATIENTS AND METHODS Depending on published data, advanced cancer was defined as cancer > or = 20 mm in size (four trials), stage II+ (four trials), and > or = one positive lymph node (one trial). For each trial, we obtained the estimated relative risk (RR) and 95% CI between the intervention and control groups, for both breast cancer mortality and diagnosis of advanced breast cancer. Using a meta-regression approach, log(RR-mortality) was regressed on log(RR-advanced cancer), weighting each trial by the reciprocal of the square of the standard error of log(RR) for mortality. RESULTS RR for advanced breast cancer ranged from 0.69 (95% CI, 0.61 to 0.78) in the Swedish Two-County Trial to 0.97 (95% CI, 0.97 to 1.25) in the Canadian National Breast Screening Study-1 (NBSS-1) trial. Log(RR)s for advanced cancer were highly predictive of log(RR)s for mortality (R(2) = 0.95; P < .0001), and the linear regression curve had a slope of 1.00 (95% CI, 0.76 to 1.25) after fixing the intercept to zero. The slope changed only slightly after excluding the Two-County Trial and the Canadian NBSS-1 and NBSS-2 trials. CONCLUSION In trials on breast cancer screening, for each unit decrease in incidence of advanced breast cancer, there was an equal decrease in breast cancer mortality. Monitoring of incidence of advanced breast cancer may provide information on the current impact of screening on breast cancer mortality in the general population.