Etiological factors in invasive corpus uteri carcinoma

The case-control method was applied in order to test how various types of diet as well as past diseases, tobacco smoking and occupational exposure may affect the risk of incidence of corpus uteri cancer in the population of natives and among immigrant women. The highest risk of incidence was noted in the group of natives persistently using a diet rich in meat, animal fat, amylum meals and sugar but lacking raw vegetables. Such a high risk was not observed in the group of immigrant women what might be caused by more frequent change of the type of diet. Some past diseases (arterial hypertension, diabetes, diseases of organs of reproduction and urinary system) do affect a relatively high risk of corpus uteri carcinoma in both populations. However, no noteworthy results have been obtained in the risk of corpus uteri carcinoma as far as tobacco smoking and occupational exposure are concerned.     

Long-term gastric cancer risk in male smokers with atrophic corpus gastritis

Objectives: The aim of this study was to evaluate long-term gastric cancer risk in male smokers with and without atrophic gastritis.

Materials and methods: A total of 22,346 elderly male smokers participated in the Helsinki Gastritis Study between the years 1989 and 1993. Serum pepsinogen I (PGI) was measured for the men, and 2,132 men with low PGI (<25 µg/L; a marker of atrophic corpus gastritis) were invited to undergo gastroscopy because of increased gastric cancer risk. Endoscopy was performed to 1,327 men, who were followed up for a median of 13.6 years and a maximum of 25.3 years thereafter. In addition, the gastric cancer risk of men with low PGI was compared to that of the men with normal PGI and to the general Finnish male population of the same age.

Results: Thirty-five cases of gastric cancer were diagnosed in men with gastroscopy during the follow-up. The incidence rate was 1.94 per 1000 patient years. The men with a history of gastric surgery (n?=?180) due to a benign cause had even higher gastric cancer incidence (3.2 per 1000 patient-years). Gastric cancer risk was highest in men with marked intestinal metaplasia in primary biopsies. Compared to the general Finnish male population of the same age, the cancer risk was 1.13 times higher in male smokers with normal serum PGI, and 2.43 times higher in men with low serum PGI.

Conclusion: In male smokers, atrophic gastritis and intestinal metaplasia increase the risk of gastric cancer.     

Larynx cancer risk factors

The larynx cancer relative risk has been evaluated (328 cases) in the stationary-native Upper Silesians (63.7%) and migrating (36.3%) male population. The particular control groups (656 men) included 418 and 238 men respectively not suffering from malignant neoplasms. The essentially higher larynx cancer incidence risk has been shown for men manual labor and exposed to the influence of various dusts, gases and vapors and other pollutants in their place of work. The increased substantial incidence risk is also true for men who smoke tobacco and are professionally exposed to the pollution. The results in regard to the consumption of raw and boiled vegetables suggest that these may be inhibitors of the neoplasmatic process in the area of larynx (although not only). The frequency of the consumption of alcohol--vodka or beer--increases the larynx cancer incidence risk both among autochthons and immigrants. Nevertheless, the data concerning the amount of alcohol consumed are less valuable here; they do not allow to establish fully reliable quantitative levels of the beer or vodka consumed. In comparison with the literature of the subject, divergent data have been obtained as far as the joint influence of drinking alcohol with simultaneous smoking of tobacco and professional exposure are concerned.     

Unopposed estrogen therapy and the risk of invasive breast cancer

BACKGROUND: Although short-term unopposed estrogen use does not seem to increase breast cancer risk, the effect of longer-term estrogen use remains unclear. We sought to assess the relationship between longer-term use of unopposed estrogen and the risk of invasive breast cancer over an extended follow-up period. METHODS: Within the Nurses' Health Study, a prospective cohort study, we observed 11 508 postmenopausal women who had a hysterectomy and reported information on estrogen use at baseline (1980). The study population was expanded every 2 years to include women who subsequently became postmenopausal and had a hysterectomy, so that 28 835 women were included in the final follow-up period (2000-2002). Estrogen use was assessed from self-reported data on biennial questionnaires. The main outcome was invasive breast cancer. RESULTS: A total of 934 invasive breast cancers were included in the analysis. Breast cancer risk increased with duration of unopposed estrogen use among longer-term users with the highest risk seen in cancers positive for estrogen receptor (ER+) and progesterone receptor (PR+). The multivariate relative risks (RRs) and 95% confidence intervals (CIs) for breast cancer with current use of unopposed estrogen for less than 5 years, 5 to 9.9 years, 10 to 14.9 years, 15 to 19.9 years, and 20 years or longer were, respectively, 0.96 (95% CI, 0.75-1.22), 0.90 (95% CI, 0.73-1.12), 1.06 (95% CI, 0.87-1.30), 1.18 (95% CI, 0.95-1.48), and 1.42 (95% CI, 1.13-1.77) (P for trend <.001). The risk of ER+/PR+ breast cancers was noted to be statistically significant after 15 years of current use (RR, 1.48; 95% CI, 1.05-2.07). CONCLUSION: Users of unopposed estrogen were at increased risk of breast cancer but only after longer-term use.     

Novel risk factors for lymph node metastasis in early invasive colorectal cancer: a multi-institution pathology review

Background

Novel risk factors for lymph node metastasis (LNM) in T1 colorectal cancer (CRC) have been recently proposed, but most have not been implemented because of the lack of validation. Here we determined the value of poorly differentiated clusters (PDCs) in a multi-institutional cohort of T1 CRC cases.

Methods

A pathology review involving 30 institutions was conducted for 3556 T1 CRCs. PDC was defined as malignant clusters comprising ≥5 cells and lacking a glandular formation. The ability to identify LNM risk was compared using Akaike’s information criterion (AIC).

Results

PDC was observed in 1401 tumors (39.4 %), including 94 (17.8 %) with <1000 µm submucosal invasion and 1307 (43.2 %) with ≥1000 µm submucosal invasion (P < 0.0001). The incidence of LNM was higher in PDC-positive tumors (17.4 %) than in PDC-negative tumors (6.9 %; P < 0.0001), and PDCs had an adverse impact on LNM irrespective of the degree of submucosal invasion. Grade 3, vascular invasion, budding, and submucosal invasion depth were also significant factors (all, P < 0.0001). AIC of risk factor to identify LNM risk was most favorable for vascular invasion (2273.4), followed by PDC (2357.4); submucosal invasion depth (2429.1) was the most unfavorable. Interinstitutional judgment disparities were smaller in PDC (kappa, 0.51) than vascular invasion (0.33) or tumor grade (0.48).

Conclusions

PDC is a promising new parameter with good ability to identify LNM risk. Use of its appropriate judgment criteria will enable us determine whether an observational policy can be safely applied following local tumor excision in T1 CRC cases.     

Risk factors in invasive cervical cancer among Mexican women

OBJECTIVE: To evaluate the association between invasive Cervical Cancer (CC) and high risk Human PapillomaVirus (HR-HPV) (viral load and type 16), along with other gynecological and socioeconomic factors. MATERIAL AND METHODS: Individually matched case-control study (215 women with invasive CC and 420 controls). The study population was recruited between 2000 and 2001. A set of variables traditionally linked with CC (gynecological and socioeconomic factors) and two variables related to HPV infection (viral load and type 16) were assessed. Hybrid Capture II was used to detect HR-HPV DNA. Viral load was measured by light measurements expressed as relative light units (RLU) and they were categorized for analysis into four groups: negative (< 1 RLU), low viral load (1-49 RLU), middle load (50-499 RLU) and high load (>499 RLU).The analysis included univariate, bivariate and multivariate techniques being the final step the estimation of Odds Ratios (OR) by means of conditional logistic regression models. Results.The probability of having invasive CC was 78 times higher in patients with infection of HR-HPV. Risk increases with HPV type 16 (OR = 429.7) as compared with other types of HR-HPV (OR = 64.1). An important trend was observed with the increase of the viral load (from 46.6 with low viral load; to 250.7 with intermediate and 612.9 with high load). The findings also indicate significant diferences in the viral load between cases and controls according to age groups and HR-HPV types (16 versus others high risk types). Finally, the partner-demographic and obstetrical variables related to the disease increased the risk of invasive CC. No association between CC and smoking was observed in this population. CONCLUSIONS: This study helps in identifying women at higher risk of developing invasive CC as a subset of those patients infected with HR-HPV. The findings point strongly to the importance of the viral load in HR-HPV as a co-factor in the development of this disease. This biomarker contributes to improving the prevention and early detection of this disease and also to identify women at higher risk who carry a high viral load of HR-HPV.     

Study of risk factors for gastric cancer by populational databases analysis

AIM:To study the association between the incidence of gastric cancer and populational exposure to risk/protective factors through an analysis of international databases.METHODS:Open-access global databases concerning the incidence of gastric cancer and its risk/protective factors were identified through an extensive search on the Web.As its distribution was neither normal nor symmetric,the cancer incidence of each country was categorized according to ranges of percentile distribution.The association of each risk/protective factor with exposure was measured between the extreme ranges of the incidence of gastric cancer(under the 25th percentile and above the 75th percentile)by the use of the Mann-Whitney test,considering a significance level of0.05.RESULTS:A variable amount of data omission was observed among all of the factors under study.A weak or nonexistent correlation between the incidence of gastric cancer and the study variables was shown by a visual analysis of scatterplot dispersion.In contrast,an analysis of categorized incidence revealed that the countries with the highest human development index(HDI)values had the highest rates of obesity in males and the highest consumption of alcohol,tobacco,fruits,vegetables and meat,which were associated with higher incidences of gastric cancer.There was no significant difference for the risk factors of obesity in females and fish consumption.CONCLUSION:Higher HDI values,coupled with a higher prevalence of male obesity and a higher per capita consumption of alcohol,tobacco,fruits,vegetables and meat,are associated with a higher incidence of gastric cancer based on an analysis of populational global data.     

Managing the risk of invasive breast cancer in women at risk for breast cancer and osteoporosis: the role of raloxifene

Raloxifene hydrochloride is a selective estrogen receptor modulator (SERM) that has antiestrogenic effects on breast and endometrial tissue and estrogenic effects on bone, lipid metabolism, and blood clotting. Raloxifene significantly improves serum lipids and serum markers of cardiovascular disease risk, but it has no significant effect on the risk of primary coronary events. A meta-analysis of randomized, double-blind, placebo-controlled trials of raloxifene for osteoporosis showed the odds of fracture risk were 0.60 (95% confidence interval [CI] = 0.49–0.74) for raloxifene 60 mg/day compared with placebo. During 8 years of follow-up in an osteoporosis trial, the raloxifene group had a 76% reduction in the incidence of invasive ER-positive breast cancer compared with the placebo group. In the STAR trial, the incidence of invasive breast cancer was 4.30 per 1000 women-years with raloxifene and 4.41 per 1000 with tamoxifen; RR = 1.02; 95% CI, 0.82–1.28. The effect of raloxifene on invasive breast cancer was, therefore, equivalent to that of tamoxifen with more favorable rates of adverse effects including uterine malignancy and clotting events. Millions of postmenopausal women could derive net benefit from raloxifene through reduced rates of fracture and invasive breast cancer.     

Occupational risk factors for cancer of the larynx in Spain

Spain is one of the countries with the highest incidence of laryngeal cancer and, together with France, is the country with the lowest percentage of women with this disease. In order to identify the occupational risk factors associated with laryngeal cancer in this country a case-control study was performed. Cases included 85 patients with epidermoid carcinoma of the larynx diagnosed in "La Paz" Hospital, Madrid, between 1985 and 1987. A sample of 170 patients from the same hospital was used as control. The results of the study revealed that 56.5% of larynx cancer patients had a sedentary occupation working in the service sector. Exposure to insecticides or silica were strongest risk factors for laryngeal cancer. An association between laryngeal cancer and exposure to fumes, chemical products, mineral dust, or wood dust was not found.     

Modifiable risk factors for colon cancer

Although many mechanisms remain unclear, a large body of evidence indicates that several dietary and lifestyle factors are likely to have a major influence on the risk of colon cancer. Physical inactivity, excess body weight, and a central deposition of adiposity are consistent risk factors. Overconsumption of energy is likely to be one of the major contributors to the high rates of colon cancer in Western countries. Beyond their influence on energy balance, the independent role of specific macronutrients remain controversial. Red meat, processed meats, and perhaps refined carbohydrates contribute to risk. Recent evidence indicate that chronic hyperinsulinemia may increase risk of colon cancer. As insulin resistance and subsequent hyperinsulinemia is induced by excess energy intake and some aspects of the Western diet (e.g., saturated fats and refined carbohydrates), insulin may be a focus of factors influencing colon cancer risk. Recent evidence also points to a role of IGF-1, but our understanding of modifiable factors that influence levels of these is poor at present. Of note is that hyperinsulinemia increases free IGF-1 exposure [25]. High alcohol consumption, probably in combination with a diet low in some micronutrients such as folate and methionine, and smoking early in life are likely to increase risk of colon cancer. Recent epidemiologic studies have tended not to support a strong influence of fiber; instead, some micronutrients or phytochemicals in fiber-rich foods may be important. Folate is one such nutrient that has received attention lately and is being studied in randomized intervention trials. Agents with chemopreventive properties, such as aspirin and postmenopausal estrogens, have potential adverse effects so a careful consideration of the risk-benefit ratio is required before general recommendations can be made. Other NSAIDs with a potential for reduced toxicity, such as celecoxib, are currently being evaluated for efficacy and toxicity. The overwhelming evidence indicates that primary prevention of colon cancer is feasible. At least 70% of colon cancers may be preventable by moderate changes in diet and lifestyle [197]. Secondary prevention, through screening by sigmoidoscopy and colonoscopy, is also critically important to prevent mortality from colon cancer; however, many of the diet and lifestyle risk factors for colon cancers are the same for cardiovascular disease and for some other cancers, so focusing on the modifiable risk factors for colon cancer is likely to have many additional benefits beyond this cancer.     

结直肠癌高危因素研究进展

恶性肿瘤严重威胁人类健康和社会经济发展,是我国乃至全球的主要公众健康问题。结直肠癌在经济发达地区较为常见,近年来一些低风险的国家由于饮食习惯、生活方式等的改变发病率也开始上升。我们查阅国内外相关文献,从社会人口学因素、医学因素、行为生活方式、饮食因素四方面对结直肠癌高危因素进行综述。     

Short-term and long-term risk factors in gastric cancer

While in chronic diseases, such as diabetes, mortality rates slowly increases with age, in oncological series mortality usually changes dramatically during the follow-up, often in an unpredictable pattern. For instance, in gastric cancer mortality peaks in the first two years of follow-up and declines thereafter. Also several risk factors, such as TNM stage, largely affect mortality in the first years after surgery, while afterward their effect tends to fade. Temporal trends in mortality were compared between a gastric cancer series and a cohort of type 2 diabetic patients. For this purpose, 937 patients, undergoing curative gastrectomy with D1/D2/D3 lymphadenectomy for gastric cancer in three GIRCG (Gruppo Italiano Ricerca Cancro Gastrico = Italian Research Group for Gastric Cancer) centers, were compared with 7148 type 2 diabetic patients from the Verona Diabetes Study. In the early/advanced gastric cancer series, mortality from recurrence peaked to 200 deaths per 1000 person-years 1 year after gastrectomy and then declined, becoming lower than 40 deaths per 1000 person-years after 5 years and lower than 20 deaths after 8 years. Mortality peak occurred earlier in more advanced T and N tiers. At variance, in the Verona diabetic cohort overall mortality slowly increased during a 10-year follow-up, with ageing of the type 2 diabetic patients. Seasonal oscillations were also recorded, mortality being higher during winter than during summer. Also the most important prognostic factors presented a different temporal pattern in the two diseases: while the prognostic significance of T and N stage markedly decrease over time, differences in survival among patients treated with diet, oral hypoglycemic drugs or insulin were consistent throughout the follow-up. Time variations in prognostic significance of main risk factors, their impact on survival analysis and possible solutions were evaluated in another GIRCG series of 568 patients with advanced gastric cancer, undergoing curative gastrectomy with D2/D3 lymphadenectomy. Survival curves in the two different histotypes (intestinal and mixed/diffuse) were superimposed in the first three years of follow-up and diverged thereafter. Likewise, survival curves as a function of site (fundus vs body/antrum) started to diverge after the first year. On the contrary, survival curves differed among age classes from the very beginning, due to different post-operative mortality, which increased from 0.5% in patients aged 65-74 years to 9.9% in patients aged 75-91 years; this discrepancy later disappeared. Accordingly, the proportional hazards assumption of the Cox model was violated, as regards age, site and histology. To cope with this problem, multivariable survival analysis was performed by separately considering either the first two years of follow-up or subsequent years. Histology and site were significant predictors only after two years, while T and N, although significant both in the short-term and in the long-term, became less important in the second part of follow-up. Increasing age was associated with higher mortality in the first two years, but not thereafter. Splitting survival time when performing survival analysis allows to distinguish between short-term and long-term risk factors. Alternative statistical solutions could be to exclude post-operative mortality, to introduce in the model time-dependent covariates or to stratify on variables violating proportionality assumption.