Response

We thank Raimondi et al. for their alternative interpretation of our results on the prognostic value of 25-hydroxyvitamin D3 (25[OH]D3) serum level in melanoma patients. With the observation that standardized value of 25(OH)D3 at diagnosis was not a prognostic factor, our major finding was that a change of 25(OH)D3 serum level upon time in both directions was associated with worse disease-free and overall survivals, with U-shaped curves. We postulated that this latter result was unlikely to be a direct consequence of vitamin D biological actions but rather reflected a global instability in patients’ metabolisms, which finally impact 25(OH)D3 serum level by any

Melanoma mortality following skin cancer screening in Germany

In 2003, a skin cancer screening campaign based on total body skin examination was launched in the federal state of Schleswig-Holstein, Germany. 20% of adults aged 20 and over were screened. In 2008, a 48% decline in melanoma mortality was reported. In the same year, skin screening was extended to the rest of Germany. We evaluated whether melanoma mortality trends decreased in Germany as compared with surrounding countries where skin screening is uncommon. We also evaluated whether the initial decreasing mortality trend observed in Schleswig-Holstein was maintained with a longer follow-up.  Regional and national melanoma mortality data from 1995 to 2013 were extracted from the GEKID database and the Federal Statistical Office. Mortality data for Germany and surrounding countries from 1980 to 2012 were extracted from the WHO mortality database.  Age-adjusted (European Standard Population) mortality rates were computed and joinpoint analysis performed for Schleswig-Holstein, Germany and surrounding countries.  In Schleswig-Holstein, melanoma mortality rates declined by 48% from 2003 to 2008, and from 2009 to 2013 returned to levels observed before screening initiation. During the 5 years of the national programme (2008-2012), melanoma mortality rates increased by 2.6% (95% CI -0.1 to 5.2) in men and 0.02% (95% CI -1.8 to 1.8) in women. No inflexion point in trends was identified after 2008 that could have suggested a decreasing melanoma mortality. Trends of cutaneous melanoma mortality in Germany from 1980 to 2012 did not differ from those observed in surrounding countries.  The transient decrease mortality in Schleswig-Holstein followed by return to pre-screening levels could reflect a temporal modification in the reporting of death causes. An in-depth evaluation of the screening programme is required

Study on potato consumption will increase confusion regarding food and the risk of gestational diabetes

Using data from the Nurses’ Health Study II, Bao and colleagues found a higher prevalence of gestational diabetes mellitus (GDM) with increasing potato consumption.1 The authors stated that the high glycaemic index of potatoes, which causes a sharp postprandial rise in blood glucose concentrations and a risk of associated pancreatic β cells exhaustion, could explain this association

Stable incidence of advanced breast cancer argues against screening effectiveness

Swedish trials on mammography screening of women aged 40-74 years indicated that two to four rounds of screening could significantly reduce the risk of being diagnosed with and dying from advanced breast cancer.1 Because stage at diagnosis is independent of treatment efficacy, the trials concluded that the introduction of screening in general populations would be reflected by a reduced incidence of advanced breast cancer and mortality from breast cancer

The forthcoming inexorable decline of cutaneous melanoma mortality in light-skinned populations

Reasons underlying time changes in cutaneous melanoma mortality in light-skinned populations are not well understood. An analysis of long-term time trends in melanoma mortality was carried out after regrouping countries in homogeneous regions.  Using the World Health Organisation (WHO) mortality database, age-period-cohort models were fitted for seven regions where the majority of population is light-skinned. Cohort effects are denoted as changes in rates occurring at different times in steadily older age groups. Period effects are denoted as changes in rates occurring simultaneously in several age groups.  Cohort effects better explained changes in melanoma mortality over time than period effects. Lifetime risk to die from melanoma increased in successive generations from 1875 until a peak year. Peak years were for subjects born in 1936-1940 in Oceania, 1937-1943 in North America, 1941-1942 in Northern Europe, 1945-1953 in the United Kingdom (UK) and Ireland, 1948 in Western Europe and 1957 in Central Europe. After peak years, lifetime risk of melanoma death gradually decreased in successive generations and risks of subjects born in 1990-1995 were back to risk levels observed for subjects born before 1900-1905. In Southern Europe, birth years with highest lifetime risk of melanoma death have not yet been attained. As time passes, melanoma deaths will steadily rarefy in younger age groups and concentrate in older age groups, for ultimately fade away after 2040-2050.  Independently from screening or treatment, over next decades, death from melanoma is likely to become an increasingly rare event. The temporary epidemic of fatal melanoma was most probably due to excessive UV-exposure of children that prevailed in 1900-1960, and mortality decreases would be due to progressive reductions in UV-exposure of children over the last decades

Physical activity, hormone replacement therapy and breast cancer risk : a meta-analysis of prospective studies

Lower risk of breast cancer has been reported among physically active women, but the risk in women using hormone replacement therapy (HRT) appears to be higher. We quantified the association between physical activity and breast cancer, and we examined the influence that HRT use and other risk factors had on this association. After a systematic literature search, prospective studies were meta-analysed using random-effect models applied on highest versus lowest level of physical activity. Dose-response analyses were conducted with studies reporting physical activity either in hours per week or in hours of metabolic equivalent per week (MET-h/week). The literature search identified 38 independent prospective studies published between 1987 and 2014 that included 116,304 breast cancer cases. Compared to the lowest level of physical activity, the highest level was associated with a summary relative risk (SRR) of 0.88 (95% confidence interval [CI] 0.85, 0.90) for all breast cancer, 0.89 (95% CI 0.83, 0.95) for ER+/PR+ breast cancer and 0.80 (95% CI 0.69, 0.92) for ER-/PR- breast cancer. Risk reductions were not influenced by the type of physical activity (occupational or non-occupational), adiposity, and menopausal status. Risk reductions increased with increasing amounts of physical activity without threshold effect. In six studies, the SRR was 0.78 (95% CI 0.70, 0.87) in women who never used HRT and 0.97 (95% CI 0.88, 1.07) in women who ever used HRT, without heterogeneity in results. Findings indicate that a physically inactive women engaging in at least 150 min per week of vigorous physical activity would reduce their lifetime risk of breast cancer by 9%, a reduction that might be two times greater in women who never used HRT. Increasing physical activity is associated with meaningful reductions in the risk of breast cancer, but in women who ever used HRT, the preventative effect of physical activity seems to be cancelled out

Variation of prostate-specific antigen value in men and risk of high-grade prostate vancer : analysis of the prostate, lung, colorectal, and ovarian cancer screening trial study

To investigate variations in prostate-specific antigen (PSA) levels among men with an initial normal PSA level in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial study. Data were extracted from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial study data set on all men in the interventional arm, with 2 tests performed in a period of < 2 years and with an initial result of the first test <4 ng/mL. The range of variation between first and second tests was computed. Risks of cancer stratified on Gleason score were computed using logistic regression. A total of 31,286 men had 2 PSA tests within 2 years and with an initial value < 4 ng/mL. From the first to the second test, the median variation of PSA levels was 3.4% (interquartile range, -15% to +26%). The variation in PSA value was not associated with the delay between the first and the second test (P = .36), age (P = .16), body mass index (P = .41), and race (P = .12). A total of 2,781 prostate cancers were diagnosed during follow-up. Adjusting for age and initial PSA level, the risk of prostate cancer increased linearly with increasing PSA level at the second test, with an odds ratio of 1.079 (95% confidence interval, 1.058-1.101) for each percent increase in PSA level. However, the variation in PSA was not associated with a higher Gleason score (P = .95 for level variations in cancer of Gleason score < 7 vs ≥ 7). Although an increase in PSA level over time is associated with increased risk of prostate cancer, this association is not related to more aggressive tumors

Trends in Breast Cancer Mortality in Sweden before and after Implementation of Mammography Screening

BACKGROUND: Incidence-based mortality modelling comparing the risk of breast cancer death in screened and unscreened women in nine Swedish counties has suggested a 39% risk reduction in women 40 to 69 years old after introduction of mammography screening in the 1980s and 1990s. OBJECTIVE: We evaluated changes in breast cancer mortality in the same nine Swedish counties using a model approach based on official Swedish breast cancer mortality statistics, robust to effects of over-diagnosis and treatment changes. Using mortality data from the NordCan database from 1974 until 2003, we estimated the change in breast cancer mortality before and after introduction of mammography screening in at least the 13 years that followed screening start. RESULTS: Breast mortality decreased by 16% (95% CI: 9 to 22%) in women 40 to 69, and by 11% (95% CI: 2 to 20%) in women 40 to 79 years of age. DISCUSSION: Without individual data it is impossible to completely separate the effects of improved treatment and health service organisation from that of screening, which would bias our results in favour of screening. There will also be some contamination of post-screening mortality from breast cancer diagnosed prior to screening, beyond our attempts to adjust for delayed benefit. This would bias against screening. However, our estimates from publicly available data suggest considerably lower benefits than estimates based on comparison of screened versus non-screened women.Peer reviewe

Active and passive smoking and risk of breast cancer : a meta-analysis

Studies on active and passive tobacco smoking and breast cancer have found inconsistent results. A meta-analysis of observational studies on tobacco smoking and breast cancer occurrence was conducted based on systematic searches for studies with retrospective (case-control) and prospective (cohort) designs. Eligible studies were identified, and relative risk measurements were extracted for active and passive tobacco exposures. Random-effects meta-analyses were used to compute summary relative risks (SRR). Heterogeneity of results between studies was evaluated using the (I (2)) statistics. For ever active smoking, in 27 prospective studies, the SRR for breast cancer was 1.10 (95 % CI [1.09-1.12]) with no heterogeneity (I (2) = 0 %). In 44 retrospective studies, the SRR was 1.08 (95 % CI [1.02-1.14]) with high heterogeneity (I (2) = 59 %). SRRs for current active smoking were 1.13 (95 % CI [1.09-1.17]) in 27 prospective studies and 1.08 (95 % CI [0.97-1.20]) in 22 retrospective studies. The results were stable across different subgroup analyses, notably pre/post-menopause, alcohol consumption adjustments, including/excluding passive smokers from the referent group. For ever passive smoking, in 11 prospective studies, the SRR for breast cancer was 1.07 (95 % CI [1.02-1.13]) with no heterogeneity (I (2) = 1 %). In 20 retrospective studies, the SRR was 1.30 (95 % CI [1.10-1.54]) with high heterogeneity (I (2) = 74 %). Too few prospective studies were available for meaningful subgroup analyses. There is consistent evidence for a moderate increase in the risk of breast cancer in women who smoke tobacco. The evidence for a moderate increase in risk with passive smoking is more substantial than a few years ago

Breast cancer mortality in neighbouring European countries with different levels of screening but similar access to treatment: trend analysis of WHO mortality database

Objective To compare trends in breast cancer mortality within three pairs of neighbouring European countries in relation to implementation of screening