Driss Ait Ouakrim

Trends in colorectal cancer mortality in Europe: retrospective analysis of the WHO mortality database

Objective To examine changes in colorectal cancer mortality in 34 European countries between 1970 and 2011. Design Retrospective trend analysis. Data source World Health Organization mortality database. Population Deaths from colorectal cancer between 1970 and 2011. Profound changes in screening and treatment efficiency took place after 1988; therefore, particular attention was paid to the evolution of colorectal cancer mortality in the subsequent period. Main outcomes measures Time trends in rates of colorectal cancer mortality, using joinpoint regression analysis. Rates were age adjusted using the standard European population. Results From 1989 to 2011, colorectal cancer mortality increased by a median of 6.0% for men and decreased by a median of 14.7% for women in the 34 European countries. Reductions in colorectal cancer mortality of more than 25% in men and 30% in women occurred in Austria, Switzerland, Germany, the United Kingdom, Belgium, the Czech Republic, Luxembourg, and Ireland. By contrast, mortality rates fell by less than 17% in the Netherlands and Sweden for both sexes. Over the same period, smaller or no declines occurred in most central European countries. Substantial mortality increases occurred in Croatia, the former Yugoslav republic of Macedonia, and Romania for both sexes and in most eastern European countries for men. In countries with decreasing mortality, reductions were more important for women of all ages and men younger than 65 years. In the 27 European Union member states, colorectal cancer mortality fell by 13.0% in men and 27.0% in women, compared with corresponding reductions of 39.8% and 38.8% in the United States. Conclusion Over the past 40 years, there has been considerable disparity in the level of colorectal cancer mortality between European countries, as well as between men and women and age categories. Countries with the largest reductions in colorectal cancer mortality are characterised by better accessibility to screening services, especially endoscopic screening, and specialised care.

Determinants of the number of mammography units in 31 countries with significant mammography screening.

In the 2000s, most of the female population of industrialised countries had access to mammography breast cancer screening, but with variable modalities among the countries. We assessed the number of mammography units (MUs) in 31 European, North American and Asian countries where significant mammography activity has existed for over 10 years, collecting data on the number of such units and of radiologists by contacting institutions in each country likely to provide the relevant information. Around 2004, there were 32 324 MU in 31 countries, the number per million women ranging from less than 25 in Turkey, Denmark, the Netherlands, the United Kingdom, Norway, Poland and Hungary to more than 80 in Cyprus, Italy, France, the United States and Austria. In a multivariate analysis, the number of MUs was positively associated with the number of radiologists (P=0.0081), the number of women (P=0.0023) and somewhat with the country surface area (P=0.077). There is considerable variation in the density of MU across countries and the number of MUs in service are often well above what would be necessary according to local screening recommendations. High number of MUs in some countries may have undesirable consequences, such as unnecessarily high screening frequency and decreased age at which screening is started.

Screening practices of unaffected people at familial risk of colorectal cancer.

Our objective was to determine screening practices of unaffected people in the general population at moderately increased and potentially high risk of colorectal cancer (CRC) because of their family history of the disease. A total of 1,627 participants in the Australasian Colorectal Cancer Family Registry study were classified into two CRC risk categories, according to the strength of their family history of the disease. We calculated the proportion of participants that adhered to national CRC screening guidelines by age group and for each familial risk category. We carried out a multinomial logistic regression analysis to evaluate the associations between screening and sociodemographic factors. Of the 1,236 participants at moderately increased risk of CRC, 70 (6%) reported having undergone guideline-defined “appropriate” screening, 251 (20%) reported some, but less than appropriate screening, and 915 (74%) reported never having had any CRC screening test. Of the 392 participants at potentially high risk of CRC, three (1%) reported appropriate screening, 140 (36%) reported some, but less than appropriate screening, and 249 (64%) reported never having had any CRC screening test. On average, those of middle age, higher education, and who had resided in Australia longer were more likely to have had screening for CRC. The uptake of recommended screening by unaffected people at the highest familial risk of developing CRC is extremely low. Guidelines for CRC screening are not being implemented in the population. More research is needed to identify the reasons so as to enable development of strategies to improve participation in screening. Cancer Prev Res; 5(2); 240–7. ©2011 AACR.

Female Hormonal Factors and the Risk of Endometrial Cancer in Lynch Syndrome

IMPORTANCE Apart from hysterectomy, there is no consensus recommendation for reducing endometrial cancer risk for women with a mismatch repair gene mutation (Lynch syndrome). OBJECTIVE To investigate the association between hormonal factors and endometrial cancer risk in Lynch syndrome. DESIGN, SETTING, AND PARTICIPANTS A retrospective cohort study included 1128 women with a mismatch repair gene mutation identified from the Colon Cancer Family Registry. Data were analyzed with a weighted cohort approach. Participants were recruited between 1997 and 2012 from centers across the United States, Australia, Canada, and New Zealand. EXPOSURES Age at menarche, first and last live birth, and menopause; number of live births; hormonal contraceptive use; and postmenopausal hormone use. MAIN OUTCOMES AND MEASURES Self-reported diagnosis of endometrial cancer. RESULTS Endometrial cancer was diagnosed in 133 women (incidence rate per 100 person-years, 0.29; 95% CI, 0.24 to 0.34). Endometrial cancer was diagnosed in 11% (n = 70) of women with age at menarche greater than or equal to 13 years compared with 12.6% (n = 57) of women with age at menarche less than 13 years (incidence rate per 100 person-years, 0.27 vs 0.31; rate difference, -0.04 [95% CI, -0.15 to 0.05]; hazard ratio per year, 0.85 [95% CI, 0.73 to 0.99]; P = .04). Endometrial cancer was diagnosed in 10.8% (n = 88) of parous women compared with 14.4% (n = 40) of nulliparous women (incidence rate per 100 person-years, 0.25 vs 0.43; rate difference, -0.18 [95% CI, -0.32 to -0.04]; hazard ratio, 0.21 [95% CI, 0.10 to 0.42]; P < .001). Endometrial cancer was diagnosed in 8.7% (n = 70) of women who used hormonal contraceptives greater than or equal to 1 year compared with 19.2% (n = 57) of women who used contraceptives less than 1 year (incidence rate per 100 person-years, 0.22 vs 0.45; rate difference, -0.23 [95% CI, -0.36 to -0.11]; hazard ratio, 0.39 [95% CI, 0.23 to 0.64]; P < .001). There was no statistically significant association between endometrial cancer and age at first and last live birth, age at menopause, and postmenopausal hormone use. CONCLUSIONS AND RELEVANCE For women with a mismatch repair gene mutation, some endogenous and exogenous hormonal factors were associated with a lower risk of endometrial cancer. These directions and strengths of associations were similar to those for the general population. If replicated, these findings suggest that women with a mismatch repair gene mutation may be counseled like the general population in regard to hormonal influences on endometrial cancer risk.

Short-Term Risk of Colorectal Cancer in Individuals With Lynch Syndrome: A Meta-Analysis

PURPOSE For carriers of germline mutations in DNA mismatch repair genes, the most relevant statistic for cancer prevention is colorectal cancer (Lynch syndrome) risk, particularly in the short term. METHODS We conducted a meta-analysis of all independent published Lynch syndrome studies reporting age- and sex-dependent colorectal cancer risks. We estimated 5-year colorectal cancer risk over different age groups, separately for male and female mutation carriers, and number needed to screen to prevent one death. RESULTS We pooled estimates from analyses of 1,114 Lynch syndrome families (508 with MLH1 mutations and 606 with MSH2 mutations). On average, one in 71 male and one in 102 female MLH1 or MSH2 mutation carriers in their 20s will be diagnosed with colorectal cancer in the next 5 years. These colorectal cancer risks increase with age, peaking in the 50s (one in seven males and one in 12 females), and then decrease with age (one in 13 males and one in 19 females in their 70s). Annual colonoscopy in 16 males or 25 females in their 50s would prevent one death from colorectal cancer over 5 years while resulting in almost no serious complications. In comparison, annual colonoscopy in 155 males or 217 females in their 20s would prevent one death while resulting in approximately one serious complication. CONCLUSION For MLH1 or MSH2 mutation carriers, current guidelines recommend colonoscopy every 1 to 2 years starting in their 20s. Our findings support this regimen from age 30 years; however, it might not be justifiable for carriers who are in their 20s.

Tumor testing to identify lynch syndrome in two Australian colorectal cancer cohorts

Tumor testing of colorectal cancers (CRC) for mismatch repair (MMR) deficiency is an effective approach to identify carriers of germline MMR gene mutation (Lynch syndrome). The aim of this study was to identify MMR gene mutation carriers in two cohorts of population‐based CRC utilizing a combination of tumor and germline testing approaches.

Quantifying the utility of single nucleotide polymorphisms to guide colorectal cancer screening

AIM To determine whether single nucleotide polymorphisms (SNPs) can be used to identify people who should be screened for colorectal cancer. METHODS We simulated one million people with and without colorectal cancer based on published SNP allele frequencies and strengths of colorectal cancer association. We estimated 5-year risks of colorectal cancer by number of risk alleles. RESULTS We identified 45 SNPs with an average 1.14-fold increase colorectal cancer risk per allele (range: 1.05-1.53). The colorectal cancer risk for people in the highest quintile of risk alleles was 1.81-times that for the average person. CONCLUSION We have quantified the extent to which known susceptibility SNPs can stratify the population into clinically useful colorectal cancer risk categories.

Multivitamin, calcium and folic acid supplements and the risk of colorectal cancer in Lynch syndrome

BACKGROUND People with a DNA mismatch repair (MMR) gene mutation have a substantially elevated risk of colorectal cancer (CRC) but the modifiers of this risk are not well established. We investigated the association between dietary supplement intake and CRC risk for carriers. METHODS This study included 1966 (56% female) carriers of an MMR gene mutation (719 MLH1, 931 MSH2, 211 MSH6 and 105 PMS2) who were recruited from the USA, Canada, Australia and New Zealand into the Colon Cancer Family Registry between 1997 and 2012. Information on lifestyle factors including supplement intake was collected at the time of recruitment. Using Cox proportional hazards regression weighted to correct for ascertainment bias, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between self-reported multivitamin, calcium and folic acid supplement intake and CRC risk. RESULTS Of 744 carriers with CRC, 18%, 6% and 5% reported intake of multivitamin, calcium and folic acid supplements for at least 1 month, respectively, compared with 27%, 11% and 10% of 1222 carriers without CRC. After adjusting for identified confounding variables, a decreased CRC risk was associated with multivitam inintake for at least 3 years (HR 0.47, 95% CI 0.32-0.69) and calcium intake for at least 3 years(HR 0.42, 95% CI 0.23-0.74), compared with never users. There was no evidence of an association between folic acid supplement intake and CRC risk (P = 0.82). CONCLUSION Intake of multivitamin and calcium supplements might be associated with a decreased risk of CRC for MMR gene mutation carriers.

Risk factors for metachronous colorectal cancer following a primary colorectal cancer: A prospective cohort study.

Individuals diagnosed with colorectal cancer (CRC) are at risk of developing a metachronous CRC. We examined the associations between personal, tumour‐related and lifestyle risk factors, and risk of metachronous CRC. A total of 7,863 participants with incident colon or rectal cancer who were recruited in the USA, Canada and Australia to the Colon Cancer Family Registry during 1997‐2012, except those identified as high‐risk, for example, Lynch syndrome, were followed up approximately every 5 years. We estimated the risk of metachronous CRC, defined as the first new primary CRC following an interval of at least one year after the initial CRC diagnosis. Observation time started at the age at diagnosis of the initial CRC and ended at the age at diagnosis of the metachronous CRC, last contact or death whichever occurred earliest, or were censored at the age at diagnosis of any metachronous colorectal adenoma. Cox regression was used to derive hazard ratios (HRs) and 95% confidence intervals (CIs). During a mean follow‐up of 6.6 years, 142 (1.81%) metachronous CRCs were diagnosed (mean age at diagnosis 59.8; incidence 2.7/1,000 person‐years). An increased risk of metachronous CRC was associated with the presence of a synchronous CRC (HR = 2.73; 95% CI: 1.30–5.72) and the location of cancer in the proximal colon at initial diagnosis (compared with distal colon or rectum, HR = 4.16; 95% CI: 2.80–6.18). The presence of a synchronous CRC and the location of the initial CRC might be useful for deciding the intensity of surveillance colonoscopy for individuals diagnosed with CRC.

Risk factors for metachronous colorectal cancer following a primary colorectal cancer

Individuals diagnosed with colorectal cancer (CRC) are at risk of developing a metachronous CRC. We examined the associations between personal, tumour‐related and lifestyle risk factors, and risk of metachronous CRC. A total of 7,863 participants with incident colon or rectal cancer who were recruited in the USA, Canada and Australia to the Colon Cancer Family Registry during 1997‐2012, except those identified as high‐risk, for example, Lynch syndrome, were followed up approximately every 5 years. We estimated the risk of metachronous CRC, defined as the first new primary CRC following an interval of at least one year after the initial CRC diagnosis. Observation time started at the age at diagnosis of the initial CRC and ended at the age at diagnosis of the metachronous CRC, last contact or death whichever occurred earliest, or were censored at the age at diagnosis of any metachronous colorectal adenoma. Cox regression was used to derive hazard ratios (HRs) and 95% confidence intervals (CIs). During a mean follow‐up of 6.6 years, 142 (1.81%) metachronous CRCs were diagnosed (mean age at diagnosis 59.8; incidence 2.7/1,000 person‐years). An increased risk of metachronous CRC was associated with the presence of a synchronous CRC (HR = 2.73; 95% CI: 1.30–5.72) and the location of cancer in the proximal colon at initial diagnosis (compared with distal colon or rectum, HR = 4.16; 95% CI: 2.80–6.18). The presence of a synchronous CRC and the location of the initial CRC might be useful for deciding the intensity of surveillance colonoscopy for individuals diagnosed with CRC.