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Background Occupational exposures in the rubber manufacturing industry showed an increased risk of cancer and have been classified as a group 1 carcinogen, largely from studies on workers employed before 1950s. Cancer sites considered as causally associated are bladder, lung and stomach, and leukaemia. Recent studies did not report an increased risk of cancer. Methods A meta-analysis was conducted on observational studies published until April 2016 on occupational exposures in the rubber manufacturing industry and risk of cancer. Case-control and cohort studies were included. Random effect models were used. Heterogeneity and publication bias were evaluated. Stratified analyses were conducted on study characteristics. Results The literature search identified 46 cohorts and 59 case-control studies. An increased risk was found for bladder cancer [standardised incidence ratio (SRR) = 1.36; 95% confidence interval (CI) 1.18, 1.57], leukaemia (SRR = 1.29; 95% CI 1.11, 1.52), lymphatic and haematopoietic system (SRR = 1.16; 95% CI 1.02, 1.31) and larynx cancer (SRR = 1.46; 95% CI 1.10, 1.94). For lung cancer, a borderline statistically significant increased risk was identified (SRR = 1.08; 95% CI 0.99, 1.17). No association was found for stomach cancer (SRR = 1.06; 95% CI 0.95, 1.17). In stratified analyses, risks of cancer were not increased for workers employed after 1960 for bladder cancer (SRR = 1.06; 95% CI 0.66, 1.71), lung cancer (SRR = 0.94; 95% CI 0.68, 1.29) or leukaemia (SRR = 0.92; 95% CI 0.62, 1.36). Conclusions Risk of bladder cancer, lung cancer, leukaemia and larynx cancer were increased among workers in rubber industry. Evidence of elevated risks was no longer seen for bladder cancer, lung cancer or leukemia among workers first employed after 1960.

Objectives Increased cancer risks have been reported among workers in the rubber manufacturing industry employed before the 1960s, but it is unclear for workers hired subsequently. The present study focused on cancer incidence among rubber workers first employed after 1975 in Sweden and the UK. Methods Two cohorts of rubber workers employed for at least 1 year were analysed. Standardised incidence ratios (SIRs), based on country-specific and period-specific incidence rates, were analysed for all cancers combined (except non-melanoma skin), bladder, lung, stomach cancer, leukaemia, non-Hodgkin9s lymphoma and multiple myeloma. Exploratory analyses were conducted for other cancers with a minimum of 10 cases in both genders combined. Results 16 026 individuals (12 441 men; 3585 women) contributed to 397 975 person-years of observation, with 846 cancers observed overall (437 in the UK, 409 in Sweden). No statistically significant increased risk was observed for any site of cancer. A reduced risk was evident for all cancers combined (SIR=0.83, 95% CI (0.74 to 0.92)), lung cancer (SIR=0.74, 95% CI (0.59 to 0.93)), non-Hodgkin9s lymphoma (SIR=0.67, 95% CI (0.45 to 1.00)) and prostate cancer (SIR=0.77, 95% CI (0.64 to 0.92)). For stomach cancer and multiple myeloma, SIRs were 0.93 (95% CI (0.61 to 1.43)) and 0.92 (95% CI 0.44 to 1.91), respectively. No increased risk of bladder cancer was observed (SIR=0.88, 95% CI (0.61 to 1.28)). Conclusions No significantly increased risk of cancer incidence was observed in the combined cohort of rubber workers first employed since 1975. Continued surveillance of the present cohorts is required to confirm absence of long-term risk and confirmatory findings from other cohorts would be important.

The CPRD has been collecting medical data among UK patients since 1987. Many studies on the risk of cancer associated with prescription of antidiabetic drugs have used the CRPD database. The objective was to compare methods and results of studies on the same exposure and outcome combination based on the CPRD.A systematic Pubmed search of articles on diabetes and cancer based on the CPRD was performed. Articles were grouped into common exposure and outcome combinations. Methods and results were compared, especially in case of diverging results between studies, with a focus on study design and statistical methods. Forty-six studies were identified. Five of them studied colorectal cancer (CRC) occurrence in diabetic patients prescribed with metformin. All studies consistently found no significant increased or decreased CRC risk associated with metformin prescription. Five studies examined the risk of bladder cancer in relation to pioglitazone prescription. Two studies found a significantly increased risk of bladder cancer, one based on the analysis of the full dataset and one based on a nested case-control design using conventional matching procedures. The three other studies found no association, all of which used propensity score matched cohort design. Four studies investigated the risk of breast cancer among insulin glargine users. The three studies that included diabetic subjects who were prescribed glargine or another insulin therapy for the first time (i.e., the new user design) found no association. The study that included past and new users of glargine and of another insulin found a significantly increased risk. Despite the use of the same data source, studies on the same exposure and outcome may arrive at markedly different conclusions. Studies using propensity scores for matching subjects or including past users in cohorts may obtain results substantially different than studies using conventional statistical approaches. Disclosure A. Koechlin: None. P. Boyle: Other Relationship; Self; Sanofi. P. Autier: Other Relationship; Self; Sanofi.

Vernez, David Koechlin, Alice Milon, Antoine Boniol, Magali Valentini, Faustine Chignol, Marie-Christine Dore, Jean-Francois Bulliard, Jean-Luc Boniol, Mathieu eng 2015/11/06 06:00 J Occup Environ Med. 2015 Nov;57(11):1192-6. doi: 10.1097/JOM.0000000000000537.; International audience; BACKGROUND: Solar ultraviolet has been recognized as the main causative factor for skin cancer and is currently classified as a carcinogenic agent by International Agency for Research on Cancer. METHOD: Results from a previous phone survey conducted in 2012 in France were used to assess exposure conditions to sun among outdoor workers. Satellite data were used in combination with an exposure model to assess anatomical exposure. RESULT: The yearly median exposure of the outdoor worker population is 77 kJ/m to 116 kJ/m. Road workers, building workers, and gardeners are the more exposed. About 70% of the yearly dose estimate is due to the cumulative summer and spring exposures. CONCLUSIONS: This study highlights the role of individual factors in anatomical exposure and ranks the most exposed body parts and outdoor occupations. Prevention messages should put emphasis on spring exposure, which is an important contributor to the yearly dose.

There is speculation on an association between sweetened, carbonated beverage consumption and cancer risk. This study aimed to examine this issue. Over 50 independent estimates of risk were available, 11 for colas specifically. A random-effects meta-analysis was carried out with tests for publication bias performed as well as Higgins and Thompson's I measure of the percentage of heterogeneity between studies that could not be explained by chance. Over all the different sites of cancer, the summary relative risk (SRR), when all 55 independent estimates were considered together, was SRR=1.03 [95% confidence interval (0.96; 1.11)]. When individual cancer sites were considered, there was no significant increase or decrease in the meta-analysis estimate of risk of cancer of the pancreas, bladder, kidney, squamous cell or adenocarcinoma of the oesophagus, colon, gastric cardia, gastric noncardia, prostate, breast, larynx and ovary or of the oral cavity, pharynx or glioma. There was no evidence in a sensitivity analysis from those studies that reported results separately for colas of an associated risk of pancreas cancer [SRR=1.00, 95% confidence interval (0.61; 1.65)]. The results for all other forms of cancers were considerably hampered by poor methodology and small numbers of studies (mainly one report on each cancer site studied). Overall, the findings are reassuring in terms of the association between soft drinks, including colas, and cancer risk, although the quality of many of the studies is quite poor by acceptable, modern standards and no study has been carried out with use of carbonated beverages as a primary hypothesis.

Objective: To describe the incidence and mortality rates from colon and rectal cancer in Midwestern Brazil. Methods: Data for the incidence rates were obtained from the Population-Based Cancer Registry (PBCR) according to the available period. Mortality data were obtained from the Mortality Information System (SIM) for the period between 1996 and 2008. Incidence and mortality rates were calculated by gender and age groups. Mortality trends were analyzed by the Joinpoint software. The age-period-cohort effects were calculated by the R software. Results: The incidence rates for colon cancer vary from 4.49 to 23.19/100,000, while mortality rates vary from 2.85 to 14.54/100,000. For rectal cancer, the incidence rates range from 1.25 to 11.18/100,000 and mortality rates range between 0.30 and 7.90/100,000. Colon cancer mortality trends showed an increase among males in Cuiabá, Campo Grande, and Goiania. For those aged under 50 years, the increased rate was 13.2% in Campo Grande. For those aged over 50 years, there was a significant increase in the mortality in all capitals. In Goiânia, rectal cancer mortality in males increased 7.3%. For females below 50 years of age in the city of Brasilia, there was an increase of 8.7%, while females over 50 years of age in Cuiaba showed an increase of 10%. Conclusion: There is limited data available on the incidence of colon and rectal cancer for the Midwest region of Brazil. Colon cancer mortality has generally increased for both genders, but similar data were not verified for rectal cancer. The findings presented herein demonstrate the necessity for organized screening programs for colon and rectal cancer in Midwestern Brazil. RESUMO: Objetivo: Descrever o perfil do câncer de cólon e reto no Centro-Oeste do Brasil. Métodos: Os dados de incidência foram obtidos dos Registros de Câncer de Base Populacional (RCBP) de acordo com o período disponível. Dados sobre os óbitos foram obtidos do Sistema de Informação em Mortalidade (SIM). As taxas de incidência e mortalidade foram calculadas por gênero e grupos etários. As tendências de mortalidade foram analisadas pelo software Joinpoint. Os efeitos de idade-período-coorte foram calculados no software R. Resultados: As taxas de incidência do câncer de cólon variaram de 4,49 a 23,19/100.000, e a mortalidade, de 2,85 a 14,54/100.000. A incidência do câncer de reto variou de 1,25 a 11,18/100.000; a mortalidade, de 0,30 a 7,90/100.000. As tendências de mortalidade por câncer de cólon mostraram um aumento entre homens em Cuiabá, Campo Grande e Goiânia. Para aqueles abaixo dos 50 anos, o aumento foi de 13,2% em Campo Grande. Para aqueles acima dos 50 anos, houve um aumento significante em todas as capitais. Em Goiânia, a mortalidade por câncer de reto em homens aumentou 7,3%. Para mulheres abaixo dos 50 anos em Brasília, o aumento foi de 8,7%, enquanto que para mulheres acima dos 50 anos em Cuiabá foi de 10%. Conclusão: Os dados de incidência do câncer de cólon e reto no Centro-Oeste do Brasil são limitados. A mortalidade por câncer de cólon tem aumentado para ambos os sexos, mas o mesmo não foi verificado para câncer de reto. Os resultados demonstram a necessidade de programas organizados de rastreamento para esta neoplasia no Centro-Oeste.

Purpose Chronic hyperinsulinemia may play a role in breast cancer etiology. We performed a meta-analysis examining whether serum concentrations of insulin and C-peptide are associated with increased breast cancer risk. Methods We restricted our analyses to prospective studies. After a systematic literature search, we computed summary relative risks (SRRs) and 95 % confidence intervals (95 % CIs) using random effect models applied to the relative risk associated with the highest versus lowest quantile of serum concentrations. We also graphically examined results in order to identify whether dose–response relationships were present. Results Six articles including 1,890 cases were retrieved for serum insulin levels and five for serum C-peptide levels including 1,759 cases. SRR and 95 % CI were 1.08 (0.66–1.78) for insulin and 1.04 (0.77–1.41) for C-peptide. Heterogeneity of results between studies was high for insulin and inexistent for C-peptide. Restricting the analysis to women diagnosed with breast cancer before or after menopause did not alter results. In insulin studies, SRR computed from relative risks not adjusted for body mass index (and other risk factors) was 1.22 (0.91–1.63). The SRR fell to 1.02 (0.53–1.97) in studies that adjusted for body mass index and other factors. Similar drops occurred in C-peptide studies, from 1.11 (0.87–1.41) to 1.06 (0.70–1.61). No consistent dose–response relationship was apparent in either pre- or post-menopausal cancers. Conclusions Our meta-analysis of observational studies found no evidence of an association between serum insulin or C-peptide concentrations and breast cancer risk. Increased risk found by some studies may have been due to inadequate control for adiposity.

After having lain dormant for a while, the association between diabetes, its risk factors and treatments, and cancer risk and death is now high on the clinical and research agenda. The microscope is currently focused on the relationships between Pioglitazone and Bladder Cancer, Exenatide and Pancreas Cancer, Liraglutide and pancreas cancer and insulin use and lung cancer. The potential association between use of insulin glargine and breast cancer risk has been the subject of recent major studies. All data regarding cancer risk and use of insulin glargine has been assembled and meta-analyses performed using state-of-the-art statistical methodology. A random effects model was employed with tests for heterogeneity (I2) and publication bias. These meta-analyses are based on reports from 21 epidemiological studies involving over one million patients and 3 million person-years of observation. Based on independent estimates from these studies, the Summary Relative Risk (SRR) for all forms of cancer was (SRR = 0.91, 95% CI (0.84, 0.99)), and for breast cancer SRR = 1.11 (95% CI (1.00, 1.48)). For new users of glargine, the SRR for breast cancer was SRR = 1.22 (95% CI (1.00, 1.48)). For colorectal cancer the SRR = 0.83 (95% CI (0.74, 0.94)) and for prostate cancer SRR = 1.14 (95% CI (0.93, 1.39)). Overall, the risk of developing cancer among users of insulin glargine is reduced compared to the risk of users of other insulins. Similarly, the risk of colorectal cancer is reduced among users of glargine. While the lower bound of the 95% confidence interval is 1.00, the risk of breast cancer does not increase with increasing duration of use of glargine. In some studies the trend in risk with increasing duration of use goes in opposite directions. The development of a detectable breast cancer from the initial carcinogenic event depends on the tumour doubling time. The time for a de novo breast cancer to become detectable ranges from 12.3 years for a doubling time of 150 days; 16.4 years for a doubling time of 200 days; and 20.5 years for a doubling time of 250 days. Most published studies have a maximum of 3–4 years of glargine use. The databases employed in these analyses were not designed for such epidemiological investigation. A major limitation is the absence of knowledge as to why a potential treatment was prescribed for an individual and why a change in therapy was indicated. Further potential limitations to this meta-analysis include that the comparison group was not the same in all studies but this could also be seen as a strength. The meta-analysis of the randomized trials had several insulin comparators and the retinopathy study had NPH as the comparator. This is not likely to invalidate the findings of this analysis nor would the fact that different adjustments were made in the individual studies. The current evidence gives no support to the hypothesis that insulin glargine is associated with an increased risk of cancer as compared to other insulins and should give reassurance to physicians and their patients. In respect to breast cancer, there is no indication of a causal association between use of insulin glargine and increased risk of breast cancer. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-13-07.

Diabetes and breast cancer are both extremely common conditions in women and may share common risk factors. It is natural to investigate any potential common risk factors and to seek biological clarification and improve prospects for prevention. Therefore, in order to help clarify the potential association between diabetes, related factors and breast cancer risk, a comprehensive literature review and formal meta-analysis was carried out, planned, conducted and reported following PRISMA guidelines regarding meta-analysis of observational studies. Variables studies in relation to breast cancer risk were adiposity, physical activity, glycaemic load, glycaemic index, diabetes, IGF-1, fasting glucose, fasting insulin and C-peptide, adiponectin and metformin and glargine use among patients with diabetes. For all variables except diabetes and breast cancer, only prospective studies were included in meta-analyses. Summary Relative Risks (SRR) and corresponding 95% Confidence Intervals (CI) were calculated from random effect models. For breast cancer at all ages, the calculated risks were as follows: diabetes (SRR = 1.27 95% CI (1.16, 1.39); physical activity (SRR = 0.88, 95% CI (0.85, 0.92)); glycaemic load (SRR = 1.06, 95% CI (1.00, 1.12)); glycaemic index (SRR = 1.04, 95% CI (0.99, 1.10)); fasting glucose (SRR = 1.12, 95% CI (1.01, 1.24)); serum insulin (SRR = 1.18, 95% CI (0.75, 1.85)); c-peptide (SRR = 1.29, 95% CI (0.91, 1.82)); adiponectin (SRR = 1.16, 95% CI (0.93, 1.46)); metformin (SRR = 1.00, 95% CI (0.69, 1.46)); and glargine (SRR = 1.11, 95% CI (1.00, 1.24)). An increase of 5 units in Body Mass Index (a weight increase if 14.5 kg in a person 1.70 metres tall) was associated in post-menopausal breast cancer (SRR = 1.12, 95% CI (1.08, 1.16)) but not at pre-menopausal ages (SRR = 0.83, 95% CI (0.72, 0.95)). Serum insulin was associated with breast cancer at post-menopausal ages but not at pre-menopausal ages whereas with c-peptide there was a significant association at pre-menopausal ages but not post-menopausal. For IGF-1, Hodge's Standardised Mean Difference (HSMD) was calculated in cohort studies and there was no significant association with breast cancer at all ages (HSMD = 0.003, 95% CI (−0.059, 0.065)), at post-menopausal ages (HSMD = −0.014, 95% CI (−0.106, 0.077)) or at pre-menopausal ages (HSMD = 0.039, 95% CI (−0.038, 0.117)). The risk of breast cancer is increased among post-menopausal women who have diabetes. Among those factors related to diabetes, key risk factors for breast cancer appear to be adiposity and lack of physical activity which are both related to the risk of developing diabetes. Action on these lifestyle factors should form the basis of a common prevention strategy. There is a need to re-evaluate potential biological mechanisms to explain the increased risk in post-menopausal women with diabetes. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-13-08.

Objective: To review and quantify the association between endogenous and exogenoustestosterone and prostate-specific antigen (PSA) and prostate cancer. Methods: Literature searches were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Prospectivecohort studies that reported data on the associations between endogenous testosterone and prostate cancer, and placebo-controlled randomized trials of testosterone replacement therapy (TRT) that reported data on PSA and/or prostate cancer cases were retained. Meta-analyses were performed using random-effects models, with tests for publication bias and heterogeneity. Results: Twenty estimates were included in a meta-analysis, which produced a summary relative risk (SRR) of prostate cancer for an increase of 5 nmol/L of testosterone of 0.99 (95% confidence interval [CI] 0.96, 1.02) without heterogeneity (I2 = 0%).Based on 26 trials, the overall difference in PSA levels after onset of use of TRT was 0.10 ng/mL (-0.28, 0.48). Results were similar when conducting heterogeneity analyses by mode of administration, region, age at baseline, baseline testosterone, trial duration, type of patients and type of TRT. The SRR of prostate cancer as an adverse effect from 11 TRT trials was 0.87 (95% CI0.30; 2.50). Results were consistent across studies. Conclusions: Prostate cancer appears to be unrelated to endogenous testosterone levels. TRT for symptomatic hypogonadism does not appear to increase PSA levels nor the risk of prostate cancer development. The current data are reassuring, although some caution is essential until multiple studies with longer follow-up are available.

Background: Increased cancer risk has been reported among workers in the rubber manufacturing industry employed before the 1960s. It is unclear whether risk remains increased among workers hired subsequently. The present study focused on risk of cancer mortality for rubber workers first employed since 1975 in 64 factories. Patients and methods: Anonymized data from cohorts of rubber workers employed for at least 1 year from Germany, Italy, Poland, Sweden, and the UK were pooled. Standardized mortality ratios (SMRs), based on country-specific death rates, were reported for bladder and lung cancer (primary outcomes of interest), for other selected cancer sites, and for cancer sites with a minimum of 10 deaths in men or women. Analyses stratified by type of industry, period, and duration of employment were carried out. Results: A total of 38 457 individuals (29 768 men; 8689 women) contributed to 949 370 person-years. No increased risk of bladder cancer was observed [SMR = 0.80, 95% confidence interval (CI) 0.46; 1.38]. The risk of lung cancer death was reduced (SMR = 0.81, 95% CI 0.70; 0.94). No statistically significant increased risk was observed for any other cause of death. A reduced risk was evident for total cancer mortality (SMR = 0.81, 95% CI 0.76; 0.87). Risks were lower for workers in the tyre industry compared with workers in the general rubber goods sector. Analysis by employment duration showed a negative trend with SMRs decreasing with increasing duration of employment. In an analysis of secondary end points, when stratified by type of industry and period of first employment, excess risks of myeloma and gastric cancer were observed each due, essentially, to results from one centre. Conclusion: No consistent increased risk of cancer death was observed among rubber workers first employed since 1975, no overall analysis of the pooled cohort produced significantly increased risk. Continued surveillance of the present cohorts is required to confirm the absence of long-term risk. © The Author 2016.

Background 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. Methods 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). Results 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. Conclusion 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.

Mullie, Patrick Koechlin, Alice Boniol, Mathieu Autier, Philippe Boyle, Peter eng England 2015/03/10 06:00 Crit Rev Food Sci Nutr. 2016 Jan 2;56(1):152-9. doi: 10.1080/10408398.2012.718723.; International audience; Breast cancer is the commonest form of cancer in women worldwide. It has been suggested that chronic hyperinsulinemia associated with insulin resistance plays a role in breast cancer etiology. To test the hyperinsulinemia hypothesis, a dietary pattern associated with a high glycemic index and glycemic load, both proxies for chronic hyperinsulinemia, should be associated with an increased risk of breast cancer. A meta-analysis restricted to prospective cohort studies was undertaken using a random effects model with tests for statistical significance, publication bias and heterogeneity. The metric for analysis was the risk of breast cancer in the highest relative to the lowest glycemic index and glycemic load dietary pattern. A dietary pattern with a high glycemic index was associated with a summary relative risk (SRR) of 1.05 (95% CI: 1.00, 1.11), and a high glycemic load with a SRR of 1.06 (95% CI: 1.00, 1.13). Adjustments for body mass index [BMI], physical activity and other lifestyle factors did not influence the SRR, nor did menopausal status and estrogen receptor status of the tumor. In conclusion, the current evidence supports a modest association between a dietary pattern with high glycemic index or glycemic load and the risk of breast cancer.

Boniol, Mathieu Koechlin, Alice Boniol, Magali Valentini, Faustine Chignol, Marie-Christine Dore, Jean-Francois Bulliard, Jean-Luc Milon, Antoine Vernez, David eng Research Support, Non-U.S. Gov't 2015/03/06 06:00 J Occup Environ Med. 2015 Mar;57(3):315-20. doi: 10.1097/JOM.0000000000000354.; International audience; OBJECTIVES: Occupational ultraviolet (UV) exposure was evaluated in a population-based sample in France. METHODS: A random survey was conducted in 2012 in individuals aged 25 to 69 years. The median daily standard erythemal UV dose (SED) was estimated from exposure time and place and matched to satellite UV records. RESULTS: A total of 889 individuals were exposed to solar UV with highest doses observed among gardeners (1.19 SED), construction workers (1.13 SED), agricultural workers (0.95 SED), and culture/art/social science workers (0.92 SED). Information and communication technology, industry, and transport workers were highly exposed (>0.70 SED). Significant factors associated with high occupational UV exposure were sex (P < 0.0001), phototype (P = 0.0003), and taking lunch outdoors (P < 0.0001). CONCLUSIONS: This study identified not only expected occupations with high UV exposure but also unexpected occupations with high exposures. This could serve as a basis for future prevention.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Careful quantitative assessment of data regarding use of mouthwash and risk of common oral conditions reveals that there is a clear evidence of benefi t from use in terms of reducing the risk of dental plaque, gingivitis, dental caries and that there are no major adverse effects including no evidence of an increased risk of oral cancer among users of mouthwash containing alcohol. Despite limitations in the quality of many studies conducted, there is a signifi cant reduction of both dental plaque and gingivitis associated with use of mouthwash preparations containing chlorhexidine or essential oils as an adjunct to standard care. The effect of mouthwash containing essential oils on both plaque and gingivitis is less than chlorhexidine in studies of less than 3 months duration but improves with increasing duration of use and equals or exceeds the effect of chlorhexidine when use is 6 months of longer. Mouthwash preparations containing cetylpyridinium or triclosan may also be effective, but less than the two former, while mouthwashes containing delmopinol are not effective for plaque and gingivitis control. How- ever, there is a large degree of heterogeneity and strong evidence of publication bias: there is a lack of small studies with a small effect of mouthwash. This results in a biased estimate of effect (over-estimated) because there is a tendency to publish mainly positive studies (those showing a strong decrease). Compared with fl uoride toothpaste used alone, topical fl uorides (mouthrinses, gels or varnishes) used in addition to fl uo- ride toothpaste reduce caries by 10% on average. Topical fl uorides (mouthrinses, gels, or varnishes) used in addition to fl uo- ride toothpaste achieve a modest reduction in caries compared to toothpaste used alone. No conclusions about any adverse effects can be reached, because such data were rarely reported in the trials. It is possible to conclude that mouthwash contain- ing fl uoride is a useful adjunct to fl uoridated toothpaste in reducing caries in children. As regards oral malignancy, quantitative analysis of mouthwash use and oral malignancy revealed no statistically signifi - cant association between mouthwash use and risk of oral cancer including no signifi cant trend in risk with increasing daily use; and no association between use of mouthwash containing alcohol and oral cancer risk. Most recent estimates of the population attributable risk for alcohol consumption and oral cancer put the fi gure at 1%. The dose of acetaldehyde from mouthwash is minute compared to that from other sources notable cigarette smoking, alco- hol drinking and certain foodstuffs including yoghurt and peas. It is extremely unlikely from a theoretical viewpoint that mouthwash could be a cause of oral cancer and this is substantiated from the lack of evidence of carcinogenicity found in epidemiological studies in humans. In summary, there is evidence supporting the use of mouthwashes in terms of preventing or reducing the risk of develop- ing a number of common conditions notably dental plaque, gingivitis and dental caries without any adverse effects. There is also evidence that mouthwash use does not increase the risk of oral cancer even when it contains a signifi cant percentage of alcohol. Mouthwash use makes a signifi cant contribution to public health.

1577Background: Lung cancer is the commonest form of cancer and diabetes is an increasingly prevalent chronic condition worldwide. Associations between these two conditions is currently the subject...

INTRODUCTION: Cancer has become a major source of morbidity and mortality globally. Despite the threat that cancer poses to public health in sub-Saharan Africa (SSA), few countries in this region have data on cancer incidence. In this paper, we present estimates of cancer incidence in Nigeria based on data from 2 population-based cancer registries (PBCR) that are part of the Nigerian national cancer registry program. MATERIALS AND METHODS: We analyzed data from 2 population based cancer registries in Nigeria, the Ibadan Population Based Cancer Registry (IBCR) and the Abuja Population Based Cancer Registry (ABCR) covering a 2 year period 2009-2010. Data are reported by registry, gender and in age groups. We present data on the age specific incidence rates of all invasive cancers and report age standardized rates of the most common cancers stratified by gender in both registries. RESULTS: The age standardized incidence rate for all invasive cancers from the IBCR was 66.4 per 100000 men and 130.6 per 100000 women. In ABCR it was 58.3 per 100000 for men and 138.6 per 100000 for women. A total of 3393 cancer cases were reported by the IBCR. Of these cases, 34% (1155) were seen among males and 66% (2238) in females. In Abuja over the same period, 1128 invasive cancers were reported. 33.6% (389) of these cases were in males and 66.4% (768) in females. Mean age of diagnosis of all cancers in men for Ibadan and Abuja were 51.1 and 49.9 years respectively. For women, mean age of diagnosis of all cancers in Ibadan and Abuja were 49.1 and 45.4 respectively. Breast and cervical cancer were the commonest cancers among women and prostate cancer the most common among men. Breast cancer age standardized incidence rate (ASR) at the IBCR was 52.0 per 100000 in IBCR and 64.6 per 100000 in ABCR. Cervical cancer ASR at the IBCR was 36.0 per 100000 and 30.3 per 100000 at the ABCR. The observed differences in incidence rates of breast, cervical and prostate cancer between Ibadan and Abuja, were not statistically significant. CONCLUSION: Cancer incidence data from two population based cancer registries in Nigeria suggests substantial increase in incidence of breast cancer in recent times. This paper highlights the need for high quality regional cancer registries in Nigeria and other SSA countries.

e12586 Background: Some observational studies have suggested links between the consumption of sugar or fructose consumption and cancer. A meta-analysis was performed of prospective studies on sugar...

e12508 Background: Efficacy of glucose-lowering medications is demonstrated in clinical trials but effectiveness in practice depends on a number of factors including the safety profile. Methods: A ...

e20022 Background: Decreasing trends in cutaneous melanoma mortality are reported in many white populations, starting before the recent advent of more efficient treatments. The objective was to for...

e12548 Background: There is speculation of possible links between sweetened carbonated beverage consumption and the risk of developing cancer. The aim of this study was to examine the association between sweetened, carbonated beverage consumption and cancer risk. Methods: PRISMA guidelines of meta-analyses were followed as closely as possible. Over 50 independent estimates of risk were available, 11 for colas specifically. A random effects meta-analysis was performed with tests for publication bias (Begg, Egger, Macaskill) performed as well as Higgins and Thompson’s I2 measure of the percentage of heterogeneity between studies which could not be explained by chance. Results: Overall the different sites of cancer, the summary relative risk (SRR) when all 56 independent estimates were considered together was SRR=1.04 (95% CI (0.96, 1.13)). On this overall scale, there appears to be no association between consumption of soft-drinks and the risk of cancer. When individual cancer sites were considered, there was no significant increase, or decrease in the meta-analysis estimate of risk of cancer of the pancreas, bladder, kidney, oesophageal squamous cell or adenocarcinoma, colon, gastric cardia, gastric non-cardia, prostate, breast, larynx and ovary nor from the oral cavity, pharynx, glioma, leukaemia or non-Hodgkin’s lymphoma where only one study was available. There was no evidence in a sensitivity analysis from those studies which reported results separately for coke, pepsi or other colas of an associated risk of pancreas cancer (SRR=1.00, 95% CI (0.61; 1.65)) based on three studies. The results for all other forms of cancers were greatly hampered by poor methodology and small numbers of studies (mainly one report on each cancer site studied). Conclusions: Overall, the findings are reassuring regarding the association between soft drinks, including colas and cancer risk, although the quality of many of the studies is quite poor by acceptable, modern standards and no study has been conducted with use of carbonated beverages as a primary hypothesis.

1510 Background: The association between diabetes, its risk factors and treatments, and cancer risk and death is now high on the clinical and research agenda. Methods: All data regarding cancer risk and use of insulin glargine has been assembled and meta-analyses performed using state-of-the-art statistical methodology. Glargine is the most studied insulin in this regard. A random effects model was employed with tests for heterogeneity (I2) and publication bias. These meta-analyses are based on reports from epidemiological studies involving a total of 907,008 diabetic subjects and 2,597,602 person-years of observation. Results: Based on independent estimates from 14 studies, the Summary Relative Risk (SRR) for all forms of cancer was (SRR=0.90, 95% CI (0.82, 0.98)) and for breast cancer SRR=1.14 (95% CI (1.00, 1.29)). For new users of glargine, from 7 studies, the SRR for breast cancer was SRR=1.20 (95% CI (0.90, 1.58)). Based on independent estimates for 9 studies, for colorectal cancer the SRR was 0.73 (95% CI (0.59, 0.91)) and for prostate cancer SRR=1.16 (95% CI (1.03, 1.30)). Overall, the risk of developing cancer among users of insulin glargine is reduced compared to the risk of users of other insulins. Similarly, the risk of colorectal cancer is reduced among users of glargine. While above unity, the risks of breast cancer and prostate cancer are increased marginally. Potential limitations to this meta-analysis include that the comparison group was not the same in all studies but this could also be seen as a strength. This is not likely to invalidate the findings of this analysis nor would the fact that different adjustments were made in the individual studies. Conclusions: The current evidence gives no support to the hypothesis that insulin glargine is associated with an increased risk of cancer as compared to other insulins and should give reassurance to physicians and their patients. Given the short exposure time possible to glargine (less than 5 years maximum), it is not biologically plausible to have a causal link to common forms of cancer.

1509 Background: Diabetes and breast cancer are both common conditions in women and may share common risk factors. Methods: To shed clarification on the potential association between diabetes, related factors and breast cancer risk, a comprehensive literature review and formal meta-analysis was carried out, planned, conducted and reported following PRISMA guidelines regarding meta-analysis of observational studies. Variables studies in relation to breast cancer risk were adiposity, physical activity, glycaemic load, glycaemic index, diabetes, IGF-1, fasting glucose, fasting insulin and C-peptide, adiponectin, metformin and glargine use. The Summary Relative Risk (SRR) and the corresponding 95% Confidence Interval (CI) was calculated. Results: For breast cancer at all ages, the calculated risks were as follows: diabetes (SRR=1.23 95% CI (1.12, 1.34); physical activity (SRR=0.88, 95% CI (0.85, 0.92)); glycaemic load (SRR=1.05, 95% CI (1.00, 1.10)); glycaemic index (SRR=1.05, 95% CI (1.00, 1.09)); fasting glucose (SRR=1.14, 95% CI (0.94, 1.37)); serum insulin (SRR=1.26, 95% CI (0.86, 1.84)); c-peptide (SRR=1.29, 95% CI (0.91, 1.82)); adiponectin (SRR=1.16, 95% CI (0.93, 1.46)); metformin (SRR=0.97, 95% CI (0.82, 1.16)); and glargine (SRR=1.10, 95% CI (0.94, 1.30)). An increase of 5 units in Body Mass Index (a weight increase if 14.5 kg in a person 1.70 metres tall) was associated in post-menopausal breast cancer (SRR=1.12, 95% CI (1.08, 1.16)) but not at pre-menopausal ages (SRR=0.83, 95% CI (0.72, 0.95)). Serum insulin was associated with breast cancer at post-menopausal ages but not at pre-menopausal ages whereas with c-peptide there was a significant association at pre-menopausal ages but not post-menopausal. For IGF-1, Hodge’s Standardised Mean Difference (HSMD) was calculated and there was no significant association with breast cancer at all ages (HSMD=-0.026, 95% CI (-0.031, 0.084)), at post-menopausal ages (HSMD=0.007, 95% CI (-0.068, 0.082)) or at pre-menopausal ages (HSMD=-0.065, 95% CI (-0.009, 0.140)). Conclusions: Key risk factors for breast cancer appear to be adiposity and physical activity which are both related to the risk of developing diabetes.

1584 Background: Considerable confusion entered the minds of physicians and patients when a database study reported an increased risk of cancer (of all forms) in diabetics using insulin glargine. S...

BACKGROUND Swedish women aged 40-69 years were gradually offered regular mammography screening since 1974, and nationwide coverage was achieved in 1997. We hypothesized that this gradual implementation of breast cancer screening would be reflected in county-specific mortality patterns during the last 20 years. METHODS Using data from the Swedish Board of Health and Welfare from 1960 to 2009, we used joinpoint regression to analyze breast cancer mortality trends in women aged 40 years and older (1,286,000 women in 1995-1996). Poisson regression models were used to compare observed mortality trends with expected trends if screening had resulted in breast cancer mortality reductions of 10%, 20%, or 30% among women screened during 18 years of follow-up after the introduction of screening. All statistical tests were two-sided. RESULTS From 1972 to 2009, breast cancer mortality rates in Swedish women aged 40 years and older declined by 0.98% annually, from 68.4 to 42.8 per 100,000, and it continuously declined in 14 of the 21 Swedish counties. In three counties, breast cancer mortality declined sharply during or soon after the implementation of screening; in two counties, a steep decline started at least 5 years after screening was introduced; and in two counties, breast cancer mortality increased after screening started. In counties in which screening started in 1974-1978, mortality trends during the next 18 years were similar to those before screening started, and in counties in which screening started in 1986-1987, mortality increased by approximately 12% (P = .007) after the introduction of screening compared with previous trends. In counties in which screening started in 1987-1988 and in 1989-1990, mortality declined by approximately 5% (P = .001) and 8% (P < .001), respectively, after the introduction of screening. Conclusion County-specific mortality statistics in Sweden are consistent with studies that have reported limited or no impact of screening on mortality from breast cancer.

Purpose Some studies have suggested an increased risk of breast cancer associated with elevated fasting serum glucose in nondiabetic subjects. Given how common both breast cancer and impaired glucose tolerance are in our aging societies, this is an important issue for public health. Methods We performed a systematic review of prospective cohort studies that examined the association between elevated serum glucose levels in nondiabetic subjects (levels below 7.0 mml/L) and the subsequent risk of breast cancer. We performed a systematic literature search and extracted relevant data in a standard way. We then computed summary relative risks (SRR) and 95 % confidence intervals using a random effects model applied on the risk of highest versus lowest quantile of serum glucose concentrations. Results Ten cohort studies were retrieved. The SRR for all studies was 1.11 (1.00–1.23), with no evidence of heterogeneity or publication bias. The SRR was not affected when the analysis was restricted to the 8 studies that reported results for fasting subjects (SRR = 1.11; 95 % CI 0.98–1.25). Three studies provided BMI-unadjusted and BMI-adjusted SRRs of 1.24 (95 % CI 0.60–2.56) and 1.20 (95 % CI 0.63–2.27), respectively. Similar magnitudes of associations were observed in sensitivity analyses, but statistical significance was lost. Conclusion In nondiabetic subjects, the risk of breast cancer associated with fasting serum glucose levels seems to be small. Potential limitations to this meta-analysis include the fact that not all studies reported risks adjusted for adiposity and that serum glucose levels of comparison groups were variable across studies.