Subsite- and stage-specific colorectal cancer trends in Estonia prior to implementation of screening

BackgroundThe occurrence of colorectal cancer (CRC) in Estonia has been characterised by increasing incidence, low survival and no screening. The study aimed to examine long-term incidence and survival trends of CRC in Estonia with specific focus on subsite and stage.MethodsWe analysed CRC incidence and relative survival using Estonian Cancer Registry data on all cases of colorectal cancer (ICD-10 C18–21) diagnosed in 1995–2014. TNM classification was used to categorise stage.ResultsAge-standardized incidence of colon cancer increased both in men and women at a rate of approximately 1% per year. Significant increase was seen for right-sided tumours, but not for left-sided tumours. Rectal cancer incidence increased significantly only in men and anal cancer incidence only in women. Age-standardized five-year relative survival for colon cancer increased from 50% in 1995–1999 to 59% in 2010–2014; for rectal cancer, from 38% to 56%. Colon cancer survival improved significantly for left-sided tumours (from 51% to 62%) and stage IV disease (from 6% to 15%). For rectal cancer, significant survival gain was seen for stage II (from 58% to 75%), stage III (from 34% to 70%) and stage IV (from 1% to 12%).ConclusionIn the pre-screening era in Estonia, increase in colon cancer incidence was limited to right-sided tumours. Large stage-specific survival gain, particularly for rectal cancer, was probably due to better staging and advances in multimodality treatment. Nonetheless, more than one quarter of new CRC cases are diagnosed at stage IV, emphasising the need for an efficient screening program.     

Colorectal cancer incidence in Germany: Stage-shift 6 years after implementation of a colonoscopy screening program

Background: In 2002, colonoscopy was introduced as a tool for colorectal cancer screening in Germany. The long-term objective was to reduce the incidence in colorectal cancer (CRC) by detection and removal of advanced adenomas. Currently, the effect of colonoscopy screening on the population-based incidence of CRC in Germany is unknown. Methods: We provide data on stage-specific (age-standardized) incidence rates in three federal states in Germany, 6 years after the implementation of colonoscopy. Results: Between 2002 and 2008 a statistically significant decrease in CRC incidence could be observed (annually 3.0%, 95% confidence interval [CI]: -3.8; -2.2). The decline could be observed in all advanced tumor categories (T2, T3, and T4), whereas the incidence of in situ carcinomas (Tis) increased annually by 51.6% (95% CI: 28.0; 79.4) until 2004, and remained stable until 2008. Conclusion: The observed changes cannot be attributed definitively to the screening activities, but the presented data support a possible causal association.     

Socioeconomic position and incidence of colorectal cancer in the Swedish population

BackgroundThe association between socioeconomic position and incidence of colorectal cancer is inconsistent and differs by global region. We aimed to clarify this association in the Swedish population.MethodsWe conducted a population-based open cohort study using data from Swedish national registers. We included all individuals, aged ≥30 years, residing in Sweden between 1993 and 2010. Socioeconomic position was indicated by (1) highest educational level (five groups), and (2) disposable income (quintiles). We used Poisson regression to estimate incidence rate ratios (IRR) and 95% confidence intervals (95% CI) of colon and rectal cancer, and colon and rectal dysplasia.ResultsIn total, 97,827,817 person-years were accumulated and 82,686 cases of colorectal cancer were diagnosed. Compared to men with ‘higher secondary’ education, the adjusted IRRs (95% CI) of rectal cancer in men with ‘primary or less’, ‘lower secondary’, ‘lower university’ or ‘higher university’ education were: 1.06 (1.00, 1.11), 1.05 (0.99, 1.10), 0.96 (0.89, 1.03), and 0.92 (0.86, 0.98), respectively. In women, the corresponding figures were: 1.04 (0.95, 1.14), 1.03 (0.94, 1.13), 0.92 (0.82, 1.02) and 0.92 (0.82, 1.02). Disposable income was not associated with rectal cancer incidence. Adjusted IRRs of colon cancer did not differ between levels of education or disposable income overall or for specific colon sub-sites. Neither education nor disposable income was consistently associated with incidence of colon or rectal dysplasia.ConclusionsPrevention strategies for colon cancer should be applicable to individuals regardless of their socioeconomic position. However, factors conferred by education, e.g., health awareness, may be important for approaches aiming to reduce inequalities in incidence of rectal cancer. Further evaluation of cancer prevention and health promotion strategies among less educated groups is warranted.     

Colorectal cancer metastatic disease progression in Australia: A population-based analysis

BackgroundNo previous Australian population-based studies have described or quantified the progression of colorectal cancer (CRC) to metastatic disease. We describe patterns of progression to metastatic disease for an Australian cohort diagnosed with localised or regional CRC.MethodsAll localised and regional CRC cases in the New South Wales Cancer Registry diagnosed during 2000–2007 were followed to December 2011 for subsequent metastases (identified by subsequent disease episode notifications) or CRC death. Cox regression was used to identify factors associated with metastatic progression.ResultsAfter a median 5.3 years follow-up, 26.4% of the 12757 cases initially diagnosed with localised or regional colon cancer had developed metastatic disease, as had 29.5% of the 7154 rectal cancer cases. For both cancer sites, risk of metastatic progression was significantly higher for those initially diagnosed with regional disease (adjusted hazard ratio [aHR] 3.49 for colon, 2.66 for rectal cancer), and for older cases (e.g. aHR for >79 years vs <60 years: 1.38 for colon, 1.69 for rectal cancer). Risk of disease progression was significantly lower for females, and varied by histology type. For colon cancer, the risk of disease progression decreased over time. For rectal cancer, risk of metastatic progression was significantly higher for those living in more socioeconomically disadvantaged areas compared with those in the least disadvantaged area.ConclusionsAn understanding of the variation in risk of metastatic progression is useful for planning health service requirements, and can help inform decisions about treatment and follow-up for colorectal cancer patients.     

A population-based age-period-cohort study of colorectal cancer incidence comparing Asia against the West

BackgroundColorectal cancer (CRC) is the third most common cancer worldwide but incidence varied widely. Despite the role of genetics, CRC is also sensitive to macro-environmental factors. Few studies have ever compared across different countries/regions to suggest possible macro-environmental risk factors of CRC. We estimated the effects of age, period and cohort on the changes of incidence of colorectal cancer across different countries/regions.MethodsPoisson regression age-period-cohort (APC) models were conducted to estimate the age, period and cohorts effects on CRC incidence across the West (i.e., the UK, the US and Australia) and Asia (i.e. Japan, Hong Kong, Shanghai, Singapore and India). We maximized the length of the study period according to each country’s data availability.ResultsWestern populations show upward inflections for their 1950s–1960s cohorts, while Asian populations (except India) show downward inflections for their 1950s cohorts. Japanese population also shows upward inflections for its 1960s cohorts, similar to the Western populations. There are apparent upward inflections towards the more recent cohorts for Hong Kong, Shanghai and Singapore; nevertheless, the confidence intervals are wider towards the more recent cohorts.ConclusionOur findings imply an increasing risk of CRC in both Western and Asian populations as their younger cohorts reach older ages. These findings are consistent with the life course argument that macro-environmental changes associated with socio-economic development have specific effects that extend over the life course. Actions that pertain to altering lifestyle-related exposures over the life course are of great importance in combating young CRC risks in the future.     

Trends in colorectal cancer incidence and related lifestyle risk factors in 15⿿49-year-olds in Canada, 1969⿿2010

BackgroundWhile the overall incidence rate of colorectal cancer (CRC) in Canada has been decreasing, some countries show an increasing incidence in those under the age of 50. We examined the trends in CRC incidence and associated lifestyle risk factors in Canadians aged 15⿿49.MethodsIncidence data for colorectal, colon and rectum/rectosigmoid cancers were obtained for 1969⿿2010 from the Canadian Cancer Registry, and trends in age-standardized incidence rates (ASIRs) were examined by Joinpoint regression for three age groups (15⿿29, 30⿿39, 40⿿49 years) and by sex. Trends in the prevalence of some CRC risk factors were similarly examined from national health surveys for various periods ranging from 1970 to 2012.ResultsIn both sexes combined, ASIRs rose by 6.7%/year (1997⿿2010) for 15⿿29-year-olds, 2.4%/year (1996⿿2010) for 30⿿39-year-olds, and 0.8%/year (1997⿿2010) for 40⿿49-year-olds. Similar trends were observed by sex. The rise in ASIR was more rapid for cancers of the rectum/rectosigmoid compared to colon for all age groups. Risk factor trends varied: excess weight rose substantially, vegetables and fruit consumption increased slightly, physical inactivity rates declined but remained high, alcohol consumption changed little, and smoking rates declined. Data on red/processed meat consumption were unavailable.ConclusionThe ASIR of CRC in young Canadians has increased since about the mid-1990s. The rising prevalence of excess weight in younger generations has likely played a role in the CRC trend, but more research is needed.     

The incidence and histo-pathological characteristics of colorectal cancer in a population based cancer registry in Zimbabwe

BackgroundData on colorectal cancer (CRC) in sub-Saharan Africa is mainly based on hospital series which suggest low incidence and frequent early onset cancers. This study characterises colorectal cancer in a population-based cancer registry in Zimbabwe.MethodsCases of CRC recorded by the Zimbabwe National Cancer Registry between 2003 and 2012 were analysed. Demographic and pathological characteristics were compared according to ethnicity and age. Trends in age standardised incidence rates (ASR) were determined.ResultsThere were 886 and 216 cases of CRC among black Africans and Caucasians respectively, and 26% of the black Africans were younger than 40 years. Signet ring cell carcinomas were more common among black Africans compared to Caucasians (4% vs 1%, p = 0.027). ASR increased by 1.9%/year and 3.9%/year among black African males and females respectively.ConclusionCRC incidence is rising among black Africans and has unique demographic and pathological characteristics.     

Stage IV colorectal cancer primary site and patterns of distant metastasis

BackgroundAlthough colorectal cancer (CRC) usually metastasizes to the liver and/or lungs, factors influencing the anatomic pattern of metastases remain poorly understood.MethodsWe assessed the relationship between primary CRC site and pattern of synchronous metastasis among 1202 individuals diagnosed with incident metastatic CRC between 2010 and 2014 and identified through the Seattle-Puget Sound Surveillance, Epidemiology, and End Results (SEER) registry. Polytomous logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between primary tumor site and synchronous metastatic pattern.ResultsCompared to patients with proximal colon primaries, patients with rectal primaries were more likely to present with lungs-only or liver and lungs metastases versus liver-only metastases (OR_{lungs–onlyvs.liver-only}: 2.39, 95% CI: 1.35–4.24, OR_{liver+lungsvs.liver-only}: 2.20, 95% CI: 1.46–3.32).ConclusionThese findings suggest that patients with rectal primaries are more likely than patients with colon primaries to present with synchronous lung metastases.     

Trends in colorectal cancer incidence in Ho Chi Minh City,Vietnam (1996–2015): Joinpoint regression and age–period–cohort analyses

BackgroundLittle is known about the trends in colorectal cancer (CRC) in Vietnam. We aimed to investigate the trends in epidemiology and anatomical subsites of CRC in Ho Chi Minh City, Vietnam.MethodsBased on the Ho Chi Minh City Cancer Registry data during 1996–2015, we calculated the average annual percent changes (AAPCs) of the age-standardized incidence rates (ASRs) by sex, age groups, and anatomical subsites, using joinpoint regressions analysis. We further performed age–period–cohort (APC) analysis using the United States National Cancer Institute’s web-based statistical tool to explore the underlying reason for the incidence trend.ResultsOver 20 years the overall ASR of CRC increased from 10.5 to 17.9 per 100,000, a 1.7-fold increase. CRC incidence elevated more rapidly in men (AAPC 4.7, 95%CI 2.2–7.3) than in women (AAPC 2.6, 95%CI 0.6–4.8). The highest and lowest increasing rates of ASRs were observed in the 50–64-year-old age group (AAPC 5.3, 95%CI 2.8–7.9) and < 50-year-old age group (AAPC 1.1, 95%CI –0.7 to 2.9), respectively. Regarding subsites, rectal cancer had the highest rate of increase (AAPC 3.3, 95%CI 1.0–5.7). Furthermore, the APC analysis indicated significant increases in CRC incidence in birth cohorts after 1975 in both genders.ConclusionsThe CRC incidence in Ho Chi Minh City increased, with the more prominent rates being among men and older populations, in rectal subsites, and in people born after 1975. The upward trend of CRC incidence in Ho Chi Minh City may be due to the adoption of a westernized lifestyle.     

Healthy lifestyle,endoscopic screening,and colorectal cancer incidence and mortality in the United States: A nationwide cohort study

BackgroundHealthy lifestyle and screening represent 2 major approaches to colorectal cancer (CRC) prevention. It remains unknown whether the CRC-preventive benefit of healthy lifestyle differs by endoscopic screening status, and how the combination of healthy lifestyle with endoscopic screening can improve CRC prevention.Methods and findingsWe assessed lifestyle and endoscopic screening biennially among 75,873 women (Nurses’ Health Study, 1988 to 2014) and 42,875 men (Health Professionals Follow-up Study, 1988 to 2014). We defined a healthy lifestyle score based on body mass index, smoking, physical activity, alcohol consumption, and diet. We calculated hazard ratios (HRs) and population-attributable risks (PARs) for CRC incidence and mortality in relation to healthy lifestyle score according to endoscopic screening. Participants’ mean age (standard deviation) at baseline was 54 (8) years. During a median of 26 years (2,827,088 person-years) follow-up, we documented 2,836 incident CRC cases and 1,013 CRC deaths. We found a similar association between healthy lifestyle score and lower CRC incidence among individuals with and without endoscopic screening, with the multivariable HR per one-unit increment of 0.85 (95% CI, 0.80 to 0.90) and 0.85 (95% CI, 0.81 to 0.88), respectively (P-interaction = 0.99). The fraction of CRC cases that might be prevented (PAR) by endoscopic screening alone was 32% (95% CI, 31% to 33%) and increased to 61% (95% CI, 42% to 75%) when combined with healthy lifestyle (score = 5). The corresponding PAR (95% CI) increased from 15% (13% to 16%) to 51% (17% to 74%) for proximal colon cancer and from 47% (45% to 50%) to 75% (61% to 84%) for distal CRC. Results were similar for CRC mortality. A limitation of our study is that our study participants are all health professionals and predominantly whites, which may not be representative of the general population.ConclusionsOur study suggests that healthy lifestyle is associated with lower CRC incidence and mortality independent of endoscopic screening. An integration of healthy lifestyle with endoscopic screening may substantially enhance prevention for CRC, particularly for proximal colon cancer, compared to endoscopic screening alone.

Kai Wang and colleagues study contributions of healthy lifestyles and endoscopic screening to colorectal cancer outcomes.     

Analysis of racial disparities in the treatment and outcomes of colorectal cancer in young adults

BackgroundThe incidence of colorectal cancer (CRC) in young adults is increasing. Minority populations with CRC are known to have worse survival outcomes. The aim of this study is to evaluate adults under age 50 years with CRC by race and ethnicity.MethodsData were obtained from all US hospitals that contributed to the National Cancer Database (NCDB) between 2004 and 2013. Univariate and multivariable testing was done to identify factors associated with patient outcome. Kaplan-Meier analysis and Cox proportional hazards models were used for association between patient characteristics and survival.ResultsA total of 83,449 patients between 18 and 50 years of age were identified. Median age was 45 years (SD ± 6), with male preponderance (53.9%). 72% were non-Hispanic Whites (NHW), Blacks (AA) were 15.1% and Hispanics (who did not identify as Blacks) were 8.3% of the study population. Distribution across stages IIV was 15.6%, 22.4%, 33.9% and 27% consecutively. 41.8% of NHW and 28.4% of AA had rectal cancers (p < 0.001). Despite equally receiving standard of care (SOC) as per national guidelines, AA had significantly lower 5-year survival rates (58.8%) compared to Hispanics (64.8%) and NHW (66.9%; HR 1.42; 1.38-1.46; p < 0.001). Furthermore, NHW (HR 0.85; 0.81-0.88; p < 0.001) and Hispanics (HR 0.75; 0.70-0.79; p < 0.001) were more likely to benefit from chemotherapy compared to AA. SOC utilization was associated with improved survival across all racial groups, especially in AA (HR 0.64; 0.60-0.69; p < 0.001).ConclusionDespite comparable rates of SOC utilization, AA young adults had worse survival outcomes compared to other races. More colon (compared to rectal) cancers in AA may have contributed to their worse outcomes.     

Age differences in presentation,diagnosis pathway and management of colorectal cancer

BackgroundThe gap in survival between older and younger European cancer patients is getting wider. It is possible that cancer in the elderly is being managed or treated differently than in their younger counterparts. This study aims to explore age disparities with respect to the clinical characteristics of the tumour, diagnostic pathway and treatment of colorectal cancer patients.MethodsWe conducted a multicenter cross sectional study in 5 Spanish regions. Consecutive incident cases of CRC were identified from pathology services. Measurements: From patient interviews, hospital and primary care clinical records, we collected data on symptoms, stage, doctors investigations, time duration to diagnosis/treatment, quality of care and treatment.Results777 symptomatic cases, 154 were older than 80 years. Stage was similar by age group. General symptoms were more frequent in the eldest and abdominal symptoms in the youngest. No differences were found regarding perception of symptom seriousness and symptom disclosure between age groups as no longer duration to diagnosis or treatment was observed in the oldest groups. In primary care, only ultrasound is more frequently ordered in those <65 years. Those >80 years had a significantly higher proportion of iron testing and abdominal XR requested in hospital. We observed a high resection rate independently of age but less adjuvant chemotherapy in Stage III colon cancer, and of radiotherapy in stage II and III rectal cancer as age increases.ConclusionThere are no relevant age disparities in the CRC diagnosis process with similar stage, duration to diagnosis, investigations and surgery. However, further improvements have to be made with respect to adjuvant therapy.     

Trend breaks in incidence of non-cardia gastric cancer in the Netherlands

IntroductionThe incidence of gastric cancer declined over the past decades. Recently, unfavorable trend breaks (i.e. rise in incidence) were seen for non-cardia cancer in younger age groups in the US. It is unclear whether these also occur in other Western countries. We aimed to analyze the gastric cancer incidence trends by age, sex, subsite and stage in the Netherlands.MethodsData on all patients with gastric adenocarcinoma diagnosed from 1973 to 2011 (n = 9093) were obtained from the population-based Eindhoven cancer registry. Incidence time trends (European standardized rates per 100,000) were separately analyzed by sex, age group (<60, 60–74, and >75 years), subsite, and pathological stage. Joinpoint analyses were performed to discern trend breaks, age–period–cohort analyses to examine the influence of longitudinal and cross-sectional changes.ResultsThe incidence of non-cardia cancer declined annually by 3.5% (95% CI −3.8; −3.3). However, in males <60 years, the incidence flattened since 2006, and tended to rise in those >74 years. This pertained to corpus cancers. The incidence of cardia cancer peaked in 1985 and decreased subsequently by 2.4% (95% CI −3.2; −1.5) yearly. The absolute incidence of stage IV disease at first diagnosis initially decreased, but then remained stable over the past 15–20 years.ConclusionsThe incidence of non-cardia cancer declined over the past four decades in the Netherlands, but now seems to be stabilizing particularly in males. Unfavorable trend breaks are seen for corpus cancer in younger and older males. The trend breaks in the Netherlands are however not similar to those observed in the US.     

Rational targeting of population groups and residential areas for colorectal cancer screening

BackgroundSociodemographic and spatial disparities in incidence and mortality burden of colorectal cancer (CRC) are important to consider in the implementation of population screening, in order to achieve expected benefit and not increase health inequities. Analytic methods should be adapted to provide rational support for targeted interventions.MethodsCRC incidence rates by tumor stage (I-IV) and location (colon vs. rectum) were analyzed for the time period 2008–2016 within a screening-relevant age interval of 55–74 years for the population of South and West Sweden, where screening is planned for. The study population was stratified by sex, country of birth, educational level (for Swedish-born citizens) and residential area. We also estimated disparities in excess mortality from CRC across groups of patients accordant to relevant population groups.ResultsThe analyses were based on 8961 patients with a first CRC diagnosis. There were marked socioeconomic gradients in the stage II-IV CRC incidence rates among Swedish-born men and women. Compared to men with high educational level, the incidence rate ratios (IRRs) of stage II, III, and IV CRC in men with low educational level were 1.38 (95% confidence interval 1.18, 1.62), 1.09 (0.95, 1.26), and 1.18 (1.02, 1.37), respectively. In women, the corresponding figures were 1.26 (1.06, 1.51), 1.19 (1.01, 1.39), and 1.45 (1.20, 1.80). The groups of patients with low educational level showed relatively high excess mortality burdens from CRC.ConclusionsOur analytic approach provided rational support for targeted intervention when implementing CRC screening, aiming at optimizing participation in groups with low educational level.     

Colorectal cancer among farmers in the AGRICAN cohort study

ObjectivesSpecific farming types and tasks have rarely been studied in relation to colorectal cancer (CRC). We evaluated associations between 5 types of livestock and 13 types of crops in relation to CRC and its subsites within the Agriculture and Cancer (AGRICAN) study.MethodsAGRICAN cohort includes 181,842 agricultural workers living in 11 French geographical areas. Data on farming types and tasks was collected by self-administered questionnaires. We identified 2 609 CRC, 972 right colon, 689 left colon and 898 rectal incident cancer cases during follow-up from 2005 to 2015. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI).ResultsSignificantly increased CRC risk was observed for farmers producing horses (HR=1.18, 95% CI 1.06–1.31), sunflower (HR=1.23, 95% CI 1.03–1.45) and field vegetables (HR=1.18, 95% CI 1.02–1.36). Positive associations were also observed for pig, poultry and wheat/barley. Some associations were observed only for specific subsites: left colon cancer was associated with fruit growing (HR=1.36, 95% CI 1.09–1.70) and potato (HR=1.28, 95% CI 1.05–1.57). Tasks related to livestock (animal care, insecticide treatment, disinfection of milking equipment and building) or to crop (haymaking, sowing, pesticide treatment, seed treatment, harvesting) were also associated with CRC. Duration and size of farming types/task increased the risk for some of the associations. Analysis stratified by sex suggested an interaction with several farming types/task.ConclusionsThe current study showed original and positive findings for several farming types and tasks and CRC risk, overall and by subsites.     

The NOTCH4-GATA4-IRG1 axis as a novel target in early-onset colorectal cancer

The early onset of colorectal cancer (CRC) in individuals younger than 50 years is an emerging phenomenon, and obesity is a strong risk factor. Inflammatory mechanisms are mediated by immune cells, with macrophages and their phenotypical changes playing a significant role in CRC. Obesity-related hormones, such as leptin and adiponectin, affect macrophage polarization and cytokine expression. Macrophage metabolism, and therefore polarization, directly affects tumor progression and survival in patients with CRC. Altered obesity-related hormone levels induce phosphoinositide kinase-3 (PI3K)/serine-threonine-protein kinase (AKT) activation in colon cancer, causing increased cell survival, hyperplasia, and proliferation. Investigating the effects of obesity-related mechanisms on PI3K/Akt signaling can provide new insights for targeting mechanisms in CRC and obesity among the young. Central molecules for the control of cell proliferation, differentiation, and tumorigenesis within the gastrointestinal tract include downstream targets of the PI3K/AKT pathway, such as Neurogenic locus notch homolog 4 (Notch4) and GATA binding proteins (GATA). Leptin and adiponectin both alter gene expression within this pathway, thereby affecting TAM-mediated CRC progression. Our goal is to introduce the NOTCH4-GATA4-IRG1 axis as a link between inflammation and sporadic CRC and to discuss this pathway as a new potential immunotherapeutic target in individuals affected with obesity and early-onset CRC.     

Mutational analysis of the hMSH6 gene in familial and early-onset colorectal and endometrial cancer in Israeli patients

Familial colorectal cancer (CRC) is noted in about 15% of incident CRC cases, and at times is hallmarked by an age at diagnosis less than 50 years. Familial adenomatous polyposis (FAP) and hereditary non-polyposis colon cancer (HNPCC) account for about 40% of familial cases. Thus, the majority of familial and early-onset CRC remain genetically elusive. Similarly, the majority of familial and early onset endometrial cancer (EC), the most prevalent extracolonic tumor in HNPCC, are genetically undefined. An attractive candidate is the hMSH6 gene. Israeli patients with early onset (age under 50 years) (n = 44) and familial nonsyndromic (n = 23) CRC, and women with familial clustering of EC or CRC (n = 12), and those diagnosed with EC at, or under, the age of 50 years (n = 5) were genotyped for germ-line mutations within the hMSH6 gene. Exon-specific PCR was followed by denaturing gradient gel electrophoresis (DGGE) analysis, complemented by DNA sequencing of abnormally migrating fragments. No patients displayed a truncating mutation, and 1 CRC patient harbored a novel missense mutation (V878A). In addition, 6 previously described polymorphisms were detected. In conclusion, mutations in the hMSH6 gene occur uncommonly in Israeli patients with familial and early-onset CRC and EC.     

Increase in breast cancer incidence among older women in Mumbai: 30-year trends and predictions to 2025

Background: Increasing trends in the incidence of breast cancer have been observed in India, including Mumbai. These have likely stemmed from an increasing adoption of lifestyle factors more akin to those commonly observed in westernized countries. Analyses of breast cancer trends and corresponding estimation of the future burden are necessary to better plan rationale cancer control programmes within the country. Methods: We used data from the population-based Mumbai Cancer Registry to study time trends in breast cancer incidence rates 1976–2005 and stratified them according to younger (25–49) and older age group (50–74). Age-period-cohort models were fitted and the net drift used as a measure of the estimated annual percentage change (EAPC). Age-period-cohort models and population projections were used to predict the age-adjusted rates and number of breast cancer cases circa 2025. Results: Breast cancer incidence increased significantly among older women over three decades (EAPC = 1.6%; 95% CI 1.1–2.0), while lesser but significant 1% increase in incidence among younger women was observed (EAPC = 1.0; 95% CI 0.2–1.8). Non-linear period and cohort effects were observed; a trends-based model predicted a close-to-doubling of incident cases by 2025 from 1300 mean cases per annum in 2001–2005 to over 2500 cases in 2021–2025. Conclusions: The incidence of breast cancer has increased in Mumbai during last two to three decades, with increases greater among older women. The number of breast cancer cases is predicted to double to over 2500 cases, the vast majority affecting older women.     

Breast cancer trends in women younger than 40 years in Brazil

BackgroundA recent Brazilian populational database analysis showed a concerning increase in breast cancer mortality rates among patients under 40 years. We aimed to evaluate the trends in the proportion of new breast cancer cases and deaths occurring in patients younger than 40 years over the last decade in Brazil.MethodsWe evaluated all consecutive breast cancer patients treated from 2009 to 2020 in a Brazilian tertiary cancer center. The proportions of new cases and deaths in patients younger than 40 years was compared between two time periods (2015–2020 versus 2009–2014) using Chi-squared test. Linear regression was used to evaluate the trends in the proportion of new cases and deaths in young patients over the years.ResultsFrom 2009 to 2020, a total of 12,569 breast cancer patients started treatment at our institution; 1441 were younger than 40 years. From 2009 to 2014, 9.9% (95% CI 9.2–10.7%) were patients younger than 40 years compared to 12.9% (95% CI 12.1–13.8%) from 2015 to 2020. Similarly, the proportion of deaths among breast cancer patients younger than 40 years increased during the period (2009–2014: 9.6%, 95% CI 7.8–11.6%; 2015–2020: 12.4%, 95% CI 10.9–14%). The linear regression model showed a trend for an increasing proportion of new breast cancer cases occurring in patients under 40 years (P = 0.005). Proportion increased from 7.9% (95% CI 6.2–9.8%) in 2009 to 21.8% (95% CI 19.1–24.8%) in 2020. The trend for the increase in the proportion of deaths in this young population was also observed in the linear regression model (P = 0.01).ConclusionsThe proportion of new breast cancer cases and deaths among patients younger than 40 years has increased in a public Brazilian cancer center over the past decade. These results raise the concern for the need to reconsider primary and secondary prevention strategies for young women.     

The impact of skin cancer prevention efforts in New South Wales,Australia: Generational trends in melanoma incidence and mortality

BackgroundIn Australia, skin cancer awareness campaigns have focused on raising the awareness and consequences of skin cancer and highlighting the importance of utilising sun protection.MethodsTrends in melanoma incidence and mortality have been explored elsewhere in Australia and this study sought to examine the trends in NSW. Anonymised incidence and mortality data for in situ and invasive melanoma from 1988 to 2014 were obtained from the NSW Cancer Registry. Trends of melanoma incidence and mortality were analysed using segmented regression to allow for changes over time. Birth cohort patterns were assessed using age–period–cohort models.ResultsOver the period, incidence of in situ melanoma increased in all age groups although the rates were lowest in those under 40 years of age. Incidence of invasive melanoma was either stable or decreased in people under 60, while it increased in those aged 60 and above, particularly in men. Age–period–cohort analysis revealed decreasing age-specific incidence of invasive melanoma under 40 years of age. Melanoma mortality over the period was stable or decreased in all groups except in men aged 60 or over. Overall, mortality rates generally declined or remained stable particularly in recent years.ConclusionIt is encouraging that rates of invasive melanoma are declining in the younger age cohorts – which could be attributed to both primary prevention efforts with individuals protecting their skin as well as early detection through self assessment and clinician performed skin checks. In addition, whilst it is important to monitor the increasing rates of in situ melanoma, the increase is likely due to early detection and treatment of melanoma that could have progressed to invasive melanoma and therefore detection whilst still in situ is an improved outcome. Overall, the results demonstrate the need to continue to improve the understanding of and compliance with primary skin cancer prevention measures in order to reduce population UVR exposure and overall melanoma incidence.