Epidemiological evidence for distinguishing subsites of colorectal cancer.

The registry of digestive tract tumours established for the department of Cote d'Or (France) was used to study the epidemiological characteristics of large bowel cancer subsites for the period 1976-1983. Age standardised incidence rates for colon cancers were 18.9/100,000 for men and 14.2/100,000 for women. The corresponding rates for rectal cancers were 18.4/100,000 and 10.2/100,000. The sex ratio for right colon cancer (caecum, ascending colon, hepatic flexure, transverse, splenic flexure) was close to 1 and did not change with advancing age, while that for the left colon (sigmoid, descending colon) showed a male excess after 65. For rectal cancer (rectosigmoid junction, rectal ampulla) the male predominance was more marked and occurred earlier, after 55 years of age. There was no significant variation in incidence between rural and urban areas for the different sublocalisations. In males the risk was high in the highest social classes for left colon cancer (p less than 0.01), and among farmers for rectal cancer (p less than 0.01). The risk of left colon cancer in males increased with the comfort of housing (p less than 0.01), but this marker of social class had little influence on incidence for the other localisations in males, or for any localisation in females. No significant variation was found with education. The incidence of colon cancer tended to increase over the 8 years of study. The variations were significant for left colon cancer. For rectal subsites cancer incidence decreased in women (p less than 0.05). The observed differences suggest differences in the aetiological factors within large bowel cancers. Therefore right colon cancer, left colon cancer and rectal cancer should be considered separately in epidemiological analytical investigations.     

Increase in the incidence of non-Hodgkin's lymphomas: evidence for a recent sharp increase in France independent of AIDS.

An increasing incidence of non-Hodgkin''s lymphoma (NHL) has been reported in several areas of the world and often correlated with the occurrence of AIDS-related lymphomas. A registry specialised in haematopoietic malignancies enabled us to report detailed time trends in the incidence of NHL over the period 1980-89. There was an overall significant increase in incidence of + 10.9% per year (P < 0.001). Such a trend was observed both in men and in women (+ 11.2% and + 10.5%, respectively) and in all age groups. It was slightly more marked in the case of high-grade tumours than for low- or intermediate-grade tumours (+ 20.0%, + 12.6% and + 12.6% respectively) and in rural than in urban areas (+ 19.6% and + 8.1% respectively). In this series, only one case was associated with an HIV infection. These data indicate that, although a significant increase in NHL incidence related to the AIDS epidemic might be expected in the near future, there is an independent dramatic trend which started earlier than the AIDS problem and the causes of which should be investigated.     

Colorectal cancer in the Department of C?te-d'Or

The present study is based on the data of the digestive tract cancer registry set up for the French department of Cote d'Or (population 455,727). During 1976-1980, 581 colon cancers and 489 rectal cancers were diagnosed. They represent 47 per cent of all recorded gastro intestinal cancers. The annual adjusted incidence rates for colon cancers, adjusted to the world population were 17.5 for males, 13.3 for females. The corresponding rates for rectal cancers were 18.2 for males, 9.7 for females. These rates rank among the high rates found in North America and Western Europe. They are particularly high for rectal cancers. There was an urban predominance for colon cancer in males. Among colorectal cancers, 75 per cent were located in the rectum or sigmoid. Sixty-one per cent of the cases of large bowel cancer underwent curative surgery. The overall 5-year survival rate was 30.0 per cent for colon cancer, 27.4 per cent for rectal cancer. After curative surgery the 5 year survival rates were respectively 53.7 per cent and 47.8 per cent. The most important determinant of survival was the pathological stage of the tumour. These results underline the fact that by its frequency and its severity, colorectal cancer represents a major cancer problem.     

Trends in the incidence of colorectal cancer at the Department of C?te-d'Or between 1976 and 1985

Colorectal cancer is the leading cause of cancer morbidity in France when both sexes are considered together. There are few available data on time trends, although such data would prove both necessary for planning screening programs and usefull to construct hypotheses on etiological factors. Data from the Registre des Tumeurs Digestives de C?te d'Or permitted to establish time trends for the different locations of colorectal cancer during the 1976-1985 period. Changes in incidence rates as based on the world reference population were studied using a log linear model as well as the Armitage test. Overall colon cancer rates have increased in both sexes. The mean annual increase of left colonic cancer was 3.1 p. 100 in men (p less than 0.05) and 4.0 p. 100 in women (NS), whereas rectal cancer decreased by 2.4 p. 100 in men and 3.3 p. 100 in women (NS). In men, left colonic cancer rates increased mainly in rural areas (+ 7.3 p. 100; p less than 0.05) whereas it increased mainly in urban areas in women (+ 6.0 p. 100; NS). In both sexes, the left colonic cancer increase was particularly noticeable in the 45-64 age group, which could indicate that the observed trend is likely to become more important in the next years. As for rectal cancer, the decrease was most important in the 65-74 age groups. That inversed trend for colon and rectum cancer has already been observed in other countries including the USA and Canada. As the trends we observed for right colon, left colon and rectal cancer differ, colorectal cancer etiology should be studied separately.     

Management by specialists of patients with digestive cancers in the Department of C?te-d'Or

The relative frequency of consultation of the different specialists involved in the diagnosis and treatment of cancer is not well known in France. This study was completed with data collected by the Digestive Tract Cancer Registry in C?te d'Or. Among 3.192 digestive tract cancers diagnosed between 1976 and 1982, 64 p. 100 were treated by gastroenterologists or surgeons. Only 18% of the patients consulted an oncologist. The frequency of consultation of gastroenterologists in the care of digestive tract cancers was independent on the location of the cancer but varied with the place of residence, fluctuating from 69.7% for patients living in the town of Dijon, to 39.9% for patients living in a town with a regional hospital without gastroenterologist. The inverse phenomenon was observed for oncologists. They treated 63.2% of the patients with esophageal cancer and 31.2 p. 100 of patients with rectal cancer, but less than 10 p. 100 of the patients with gastric, colonic, liver, biliary tract or pancreatic cancer. The number of surgeons consulted depended essentially on the operability of the cancer. Between 1976 and 1982 consultation with gastroenterologists and surgeons by patients with digestive tract cancer increased by 4.4 p. 100 (p less than 0.05) and 2.1 p. 100 per year (p less than 0.01), respectively. The frequency of consultation of oncologists remained stable: +0.3 p. 100 per year. These results confirm the importance of a training policy oriented towards specialists who are not oncologists. They must take note of their importance in the diagnosis and the organization of the fight against digestive tract cancers.     

Rectocolonic cancers in young patients. A population study (C?te-d'Or: 1976-1983

Between 1976 and 1983, 1,783 colorectal cancers were diagnosed among the Cote-d'Or residents; of these 44 (2.5 p. 100) were under age 45. Cancer developed more often on familial polyposis (11.4 p. 100), ulcerative colitis (2.3 p. 100) or in the Lynch cancer family syndrome (4.6 p. 100) before 45 than in older patients: 0.2 p. 100 (p less than 0.01), 0.2 p. 100 (NS) and 0 p. 100 (p less than 0.01) respectively. There was no significant difference between young and older patients concerning the site, the histologic type or the stage of diagnosis. Curative resection rates were similar before age 45 (68.2 p. 100) as after that age (61.8 p. 100). Operative mortality was lower in younger (3.3 p. 100) than in older patients (12.6 p. 100; NS). After surgery for cure (operative mortality excluded) the 5-year corrected survival rates were similar in the two age groups: 69.4 +/- 8.8 p. 100 and 64.0 +/- 1.8 p. 100 respectively (NS). These data suggest that with the exception of predisposing diseases there is no important difference between young and older patients with regard to the anatomoclinical and evolutive aspects of colorectal cancers.     

Different multiple regression models for estimating survival: use in a population-based series of colorectal cancers.

Two additive models for estimating relative survival, recently available in statistical packages, were compared to the Cox model in order to define practical criteria for choosing one of these three models. The three models were applied to a series of 1062 colorectal cancer incident cases recorded at the "Registre des Tumeurs Digestives de C?te d'Or" to study the impact on survival of age, sex and socio-economic status. The respective advantages of each method and facilities of each program were identified. This study emphasized the importance of multiple regression models for estimating relative survival: from the epidemiologist's point of view, they reinforce the validity of international comparisons of survival statistics, from the clinician's point of view, they permit to identify the real prognostic significance of variables related to life expectancy in the general population.     

Dietary intakes of ω‐6 and ω‐3 polyunsaturated fatty acids and the risk of breast cancer

Experimental studies suggest detrimental effects of ω‐6 polyunsaturated fatty acids (PUFA), and beneficial effects of ω‐3 PUFAs on mammary carcinogenesis, possibly in interaction with antioxidants. However, PUFA food sources are diverse in human diets and few epidemiologic studies have examined whether associations between dietary PUFAs and breast cancer risk vary according to food sources or antioxidant intakes. The relationship between individual PUFA intakes estimated from diet history questionnaires and breast cancer risk was examined among 56,007 French women. During 8 years of follow‐up, 1,650 women developed invasive breast cancer. Breast cancer risk was not related to any dietary PUFA overall; however, opposite associations were seen according to food sources, suggesting other potential effects than PUFA per se. Breast cancer risk was inversely associated with α‐linolenic acid (ALA) intake from fruit and vegetables [highest vs. lowest quintile, hazard ratio (HR) 0.74; 95% confidence interval (CI) 0.63, 0.88; p trend < 0.0001], and from vegetable oils (HR 0.83; 95% CI 0.71, 0.97; p trend 0.017). Conversely, breast cancer risk was positively related to ALA intake from nut mixes (p trend 0.004) and processed foods (p trend 0.068), as was total ALA intake among women in the highest quintile of dietary vitamin E (p trend 0.036). A significant interaction was also found between ω‐6 and long‐chain ω‐3 PUFAs, with breast cancer risk inversely related to long‐chain ω‐3 PUFAs in women belonging to the highest quintile of ω‐6 PUFAs (p interaction 0.042). These results emphasize the need to consider food sources, as well as interactions between fatty acids and with antioxidants, when evaluating associations between PUFA intakes and breast cancer risk. © 2008 Wiley‐Liss, Inc.     

A prospective study of one‐carbon metabolism biomarkers and cancer of the head and neck and esophagus

Experimental and epidemiological data suggest that factors of one‐carbon metabolism are important in the pathogenesis of several cancers, but prospective data on head and neck cancer (HNC) and esophagus cancer are limited. The European Prospective Investigation into Cancer and Nutrition (EPIC) study recruited 385,747 participants from 10 countries who donated a blood sample. The current study included 516 cancer cases of the head and neck and esophagus and 516 individually matched controls. Plasma levels of vitamins B2, B6, B9 (folate), B12, and methionine and homocysteine were measured in pre‐diagnostic plasma samples and analyzed in relation to HNC and esophagus cancer risk, as well as post‐diagnosis all‐cause mortality. After controlling for risk factors, study participants with higher levels of homocysteine had elevated risk of HNC, the odds ratio (OR) in conditional analysis when comparing the top and bottom quartiles of homocysteine [OR_{Q4vs. Q1}] being 2.13 (95% confidence interval [95% CI] 1.13–4.00, p for trend 0.009). A slight decrease in HNC risk was also seen among subjects with higher levels of folate (OR_{Q4vs. Q1} 0.63, 95% CI 0.35–1.16, p for trend 0.02). Subgroup analyses by anatomical sub‐site indicated particularly strong associations with circulating homocysteine for oral cavity and gum cancer (p for trend 8 × 10^?4), as well as for oropharynx cancer (p for trend 0.008). Plasma concentrations of the other investigated biomarkers did not display any clear association with risk or survival. In conclusion, study participants with elevated circulating levels of homocysteine had increased risk of developing squamous cell carcinoma of the head and neck.     

Plasma microRNAs as biomarkers of pancreatic cancer risk in a prospective cohort study

Noninvasive biomarkers for early pancreatic ductal adenocarcinoma (PDAC) diagnosis and disease risk stratification are greatly needed. We conducted a nested case‐control study within the Prospective Investigation into Cancer and Nutrition (EPIC) cohort to evaluate prediagnostic microRNAs (miRs) as biomarkers of subsequent PDAC risk. A panel of eight miRs (miR‐10a, ‐10b, ‐21‐3p, ‐21‐5p, ‐30c, ‐106b, ‐155 and ‐212) based on previous evidence from our group was evaluated in 225 microscopically confirmed PDAC cases and 225 controls matched on center, sex, fasting status and age/date/time of blood collection. MiR levels in prediagnostic plasma samples were determined by quantitative RT‐PCR. Logistic regression was used to model levels and PDAC risk, adjusting for covariates and to estimate area under the receiver operating characteristic curves (AUC). Plasma miR‐10b, ‐21‐5p, ‐30c and ‐106b levels were significantly higher in cases diagnosed within 2 years of blood collection compared to matched controls (all p‐values <0.04). Based on adjusted logistic regression models, levels for six miRs (miR‐10a, ‐10b, ‐21‐5p, ‐30c, ‐155 and ‐212) overall, and for four miRs (‐10a, ‐10b, ‐21‐5p and ‐30c) at shorter follow‐up time between blood collection and diagnosis (≤5 yr, ≤2 yr), were statistically significantly associated with risk. A score based on the panel showed a linear dose‐response trend with risk (p‐value = 0.0006). For shorter follow‐up (≤5 yr), AUC for the score was 0.73, and for individual miRs ranged from 0.73 (miR‐212) to 0.79 (miR‐21‐5p).