Isoflavone and Soyfood Intake and Colorectal Cancer Risk: A Case-Control Study in Korea

We aimed to assess the relationship between dietary soyfood and isoflavone intake and colorectal cancer risk in a case-control study. A total of 901 colorectal cancer cases and 2669 controls were recruited at the National Cancer Center, Korea. A semi-quantitative food frequency questionnaire was used to assess the usual dietary habits, and the isoflavone intake level was estimated from five soyfood items. A high intake of total soy products, legumes, and sprouts was associated with a reduced risk for colorectal cancer in men and women, although the middle quartiles of intake of total soy products were associated with an elevated risk. In contrast, a high intake of fermented soy paste was associated with an elevated risk for colorectal cancer in men. The groups with the highest intake quartiles of isoflavones showed a decreased risk for colorectal cancer compared to their counterparts with the lowest intake quartiles in men (odds ratio (OR): 0.67, 95% confidence interval (CI): 0.51–0.89) and women (OR: 0.65, 95% CI: 0.43–0.99). The reduced risk for the highest intake groups persisted for distal colon cancer in men and rectal cancer in women. The association between soyfood intake and colorectal cancer risk was more prominent among post-menopausal women than pre-menopausal women. In conclusion, a high intake of total soy products or dietary isoflavones was associated with a reduced risk for overall colorectal cancer, and the association may be more relevant to distal colon or rectal cancers.     

Processed and Unprocessed Red Meat and Risk of Colorectal Cancer: Analysis by Tumor Location and Modification by Time

Although the association between red meat consumption and colorectal cancer (CRC) is well established, the association across subsites of the colon and rectum remains uncertain, as does time of consumption in relation to cancer development. As these relationships are key for understanding the pathogenesis of CRC, they were examined in two large cohorts with repeated dietary measures over time, the Nurses’ Health Study (n = 87,108 women, 1980–2010) and Health Professionals Follow-up Study (n = 47,389 men, 1986–2010). Cox proportional hazards regression models generated hazard ratios (HRs) and 95% confidence intervals (CIs), which were pooled by random-effects meta-analysis. In combined cohorts, there were 2,731 CRC cases (1,151 proximal colon, 816 distal colon, and 589 rectum). In pooled analyses, processed red meat was positively associated with CRC risk (per 1 serving/day increase: HR = 1.15, 95% CI: 1.01–1.32; P for trend 0.03) and particularly with distal colon cancer (per 1 serving/day increase; HR = 1.36; 95% CI: 1.09–1.69; P for trend 0.006). Recent consumption of processed meat (within the past 4 years) was not associated with distal cancer. Unprocessed red meat was inversely associated with risk of distal colon cancer and a weak non-significant positive association between unprocessed red meat and proximal cancer was observed (per 1 serving/day increase: distal HR = 0.75; 95% CI: 0.68–0.82; P for trend <0.001; proximal HR = 1.14, 95% CI: 0.92–1.40; P for trend 0.22). Thus, in these two large cohorts of US health professionals, processed meat intake was positively associated with risk of CRC, particularly distal cancer, with little evidence that higher intake of unprocessed red meat substantially increased risk of CRC. Future studies, particularly those with sufficient sample size to assess associations by subsites across the colon are needed to confirm these findings and elucidate potentially distinct mechanisms underlying the relationship between processed meat and subtypes of unprocessed red meat with CRC.     

Colorectal cancer incidence in 5 Asian countries by subsite: An analysis of Cancer Incidence in Five Continents (1998–2007)

Colorectal cancer is the fourth most common cancer in Asia. However, the trends in colorectal cancer incidence by subsite have not been analyzed across Asian countries. We used the most recent, high quality data from 6 cancer registries for two 5-year periods, 1998–2002 and 2003–2007, from Cancer Incidence in Five Continents to estimate colorectal cancer incidence by subsite in 5 Asian countries. Cases with overlapping lesions or otherwise unspecified colon cancer were re-distributed as proximal or distal colon cancer. Age-standardized incidence rates (ASRs) per 100,000 population and incidence rate ratios from 1998 to 2002 to 2003–2007 were calculated for each subsite. For 2003–2007, men in Miyagi, Japan, had the highest ASR for cancer in the proximal colon, distal colon and rectum. Men of Jewish ancestry in Israel had a high ASR for proximal and distal colon cancer, but the lowest ASR for rectal cancer. The proportion of rectal cancer was highest among Korean men (51.39%) and lowest among Israeli women (26.6%). From 1998–2002 to 2003–2007, rectal cancer incidence did not significantly change in most registries, except for men in Miyagi, Japan, and both sexes in Korea. However, during the same period cancer incidence in the proximal and distal colon increased in most registries. In conclusion, there was substantial variation in subsite distributions of colorectal cancer in Asian registries and increases in overall incidence of colorectal cancer could be attributed to increases in colon cancer.     

Sedentary work and the risks of colon and rectal cancer by anatomical sub-site in the Canadian census health and environment cohort (CanCHEC)

BackgroundSedentary behaviour is a potential risk factor for colorectal cancer. We examined the association between sedentary work, based on body position, and colorectal cancer risk in Canadians.MethodsA working body position category (a. sitting; b. standing and walking; c. sitting, standing, and walking; d. other) was assigned to occupations reported by 1991 Canadian Census respondents based on national occupational counselling guidelines. Adjusted hazard ratios (HRs) and 95% confidence intervals (CI) were estimated for cancers of the colon (overall, proximal, and distal) and rectum in men and women newly diagnosed from 1992 to 2010.ResultsCompared to “sitting” jobs, men in occupations with “other” (non-sitting, −standing, or −walking) body positions had a weakly significant reduced colon cancer risk (HR = 0.93, 95% CI: 0.89, 0.98) primarily attributed to protection at the distal site (HR = 0.90, 95% CI: 0.84, 0.97). Men in “standing and walking” and “sitting, standing, and walking” jobs did not have significantly reduced colon cancer risks. No effects were observed for rectal cancer in men or colon and rectal cancer in women.ConclusionThe two significant findings of this analysis should be followed-up in further investigations with additional information on potential confounders. Null findings for rectal cancer were consistent with other studies.     

Colorectal cancer risk and dyslipidemia: A case–cohort study nested in an Italian multicentre cohort

BackgroundDyslipidemia is an established risk factor for many diseases, but its effect on colorectal cancer risk is less clear. We investigated the association of colorectal cancer risk with plasma triglycerides, total, HDL, and LDL cholesterol in four Italian EPIC centers.MethodsWe conducted a case–cohort study on participants recruited to four Italian EPIC centers (Turin, Varese, Naples, and Ragusa; 34,148 subjects). A random subcohort of 850 subjects was obtained and 286 colorectal cancer cases were diagnosed. Triglycerides, total and HDL cholesterol were determined in plasma samples obtained at baseline and stored at −196 °C; LDL cholesterol was calculated. Hazard ratios (HR) with 95% confidence intervals (CI), adjusted for potential confounders, were estimated by Cox regression models using the Prentice method.ResultsThe highest tertiles of total (HR 1.66, 95%CI 1.12–2.45) and LDL cholesterol (HR 1.87, 95%CI 1.27–2.76) were associated with increased colorectal cancer risk compared to lowest tertiles. Risks were greater for men than women, and for postmenopausal than premenopausal women. Highest tertiles of total and LDL cholesterol were also significantly associated with increased risks of colon cancer, distal colon cancer, and rectal cancer, but not proximal colon cancer.ConclusionsOur findings suggest that high levels of total and LDL cholesterol increase colorectal cancer risk, particularly in men and postmenopausal women. However additional studies are needed to clarify the role of plasma lipids in these cancers, particularly in view of the conflicting findings of previous studies.     

Alterations in vasomotor systems and mechanics of resistance-sized mesenteric arteries from SHR and WKY male rats following in vivo testosterone manipulation

Background

It remains unclear whether the increased risk of colorectal cancer (CRC) associated with obesity differs by gender, distribution of fat, tumour location and clinical (TNM) stage. The primary aim of this study was to examine these associations in 584 incident colorectal cancer cases from a Swedish prospective population-based cohort including 28098 men and women.

Methods

Seven anthropometric factors; height, weight, bodyfat percentage, hip circumference, waist circumference, BMI and waist-hip ratio (WHR) were categorized into quartiles of baseline anthropometric measurements. Relative risks of CRC, total risk as well as risk of different TNM stages, and risk of tumours located to the colon or rectum, were calculated for all cases, women and men, respectively, using multivariate Cox regression models.

Results

Obesity, as defined by all anthropometric variables, was significantly associated with an overall increased risk of CRC in both women and men. While none of the anthropometric measures was significantly associated with risk of tumour (T)-stage 1 and 2 tumours, all anthropometric variables were significantly associated with an increased risk of T-stage 3 and 4, in particular in men. In men, increasing quartiles of weight, hip, waist, BMI and WHR were significantly associated with an increased risk of lymph node positive (N1 and N2) disease, and risk of both non-metastatic (M0) and metastatic (M1) disease. In women, there were no or weak associations between obesity and risk of node-positive disease, but statistically significant associations between increased weight, bodyfat percentage, hip, BMI and M0 disease. Interestingly, there was an increased risk of colon but not rectal cancer in men, and rectal but not colon cancer in women, by increased measures of weight, hip-, waist circumference and bodyfat percentage.

Conclusions

This study is the first to show a relationship between obesity, measured as several different anthropometric factors, and an increased risk of colorectal cancer of more advanced clinical stage, in particular in men. These findings suggest that risk of CRC differs according to the method of characterising obesity, and also according to gender, location, and tumour stage.     

Molecular Pathway Analysis Indicates a Distinct Metabolic Phenotype in Women With Right-Sided Colon Cancer

Colon cancer is the third most commonly diagnosed cancer in the United States. Recent reports have shown that the location of the primary tumor is of clinical importance. Patients with right-sided colon cancers (RCCs) (tumors arising between the cecum and proximal transverse colon) have poorer clinical outcomes than those with left-sided colon cancers (LCCs) (tumors arising between the distal transverse colon and sigmoid colon, excluding the rectum). Interestingly, women have a lower incidence of colon cancer than men, but have a higher propensity for RCC. The reason for this difference is not known; however, identification of sex-specific differences in gene expression by tumor anatomical location in the colon could provide further insight. Moreover, it could reveal important predictive markers for response to various treatments. This study provides a comprehensive bioinformatic analysis of various genes and molecular pathways that correlated with sex and anatomical location of colon cancers using four publicly available annotated data sets housed in the National Center for Biotechnology Information's Gene Expression Omnibus. We identified differentially expressed genes in tumor tissues from women with RCC, which showed attenuated energy and nutrient metabolism when compared with women with LCC. Specifically, we showed the downregulation of 5′ AMP-activated protein kinase alpha subunit (AMPKα) and anti-tumor immune responses in women with RCC. This difference was not seen when comparing tumor tissues from men with RCC to men with LCC. Therefore, women with RCC may have a specific metabolic and immune phenotype which accounts for differences in prognosis and treatment response.     

Micronutrient intake and risk of colon and rectal cancer in a Danish cohort

Background: Micronutrients may protect against colorectal cancer. Especially folate has been considered potentially preventive. However, studies on folate and colorectal cancer have found contradicting results; dietary folate seems preventive, whereas folic acid in supplements and fortification may increase the risk. Objective: To evaluate the association between intake of vitamins C, E, folate and beta-carotene and colorectal cancer risk, focusing on possibly different effects of dietary, supplemental and total intake, and on potential effect modification by lifestyle factors. Design: In a prospective cohort study of 56,332 participants aged 50–64 years, information on diet, supplements and lifestyle was collected through questionnaires. 465 Colon and 283 rectal cancer cases were identified during follow-up. Incidence rate ratios of colon and rectal cancers related to micronutrient intake were calculated using Cox proportional hazard analyses. Results: The present study found a protective effect of dietary but not supplemental folate on colon cancer. No association with any other micronutrient was found. Rectal cancer did not seem associated with any micronutrient. For both colon and rectal cancer, we found an interaction between dietary folate and alcohol intake, with a significant, preventive effect among those consuming above 10 g alcohol/day only. Conclusions: This study adds further weight to the evidence that dietary folate protects against colon cancer, and specifies that there is a source-specific effect, with no preventive effect of supplemental folic acid. Further studies should thus take source into account. Vitamins C, E and beta-carotene showed no relation with colorectal cancer.     

Choline and Betaine Intake and Colorectal Cancer Risk in Chinese Population: A Case-Control Study

Background

Few studies have examined the association of choline and betaine intake with colorectal cancer risk, although they might play an important role in colorectal cancer development because of their role as methyl donors. The aim of this study was to examine the relationship between consumption of choline and betaine and colorectal cancer risk in a Chinese population.

Methodology/Principal Findings

A case-control study was conducted between July 2010 and December 2013 in Guangzhou, China. Eight hundred and ninety consecutively recruited colorectal cancer cases were frequency matched to 890 controls by age (5-year interval) and sex. Dietary information was assessed with a validated food frequency questionnaire by face-to-face interviews. The logistic regression model was used to estimate multivariate odds ratios (ORs) and 95% confidence intervals (CIs). Total choline intake was inversely associated with colorectal cancer risk after adjustment for various lifestyle and dietary factors. The multivariate-adjusted OR was 0.54 (95%CI = 0.37-0.80, Ptrend <0.01) comparing the highest with the lowest quartile. No significant associations were observed for betaine or total choline+betaine intakes. For choline-containing compounds, lower colorectal cancer risk was associated with higher intakes of choline from phosphatidylcholine, glycerophosphocholine and sphingomyelin but not for free choline and phosphocholine. The inverse association of total choline intake with colorectal cancer risk was observed in both men and women, colon and rectal cancer. These inverse associations were not modified by folate intake.

Conclusions

These results indicate that high intake of total choline is associated with a lower risk of colorectal cancer.     

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.     

Lifestyle factors and Ki-ras mutations in colon cancer tumors

Heterogeneity in colon tumors implies that environmental, lifestyle, or genetic factors influence the type of mutations seen in tumors. In this study we evaluate the association between previously identified risk factors for colon cancer and Kirsten-ras (Ki-ras) mutations in tumors. The presence of Ki-ras mutations in codons 12 and 13 were determined in a population-based case-control study of colon cancer. Participants were between 30 and 79 years of age at time of diagnosis and include both men and women. Questionnaire data were used to obtain information on lifestyle factors. Valid study data and Ki-ras mutational status were available from 1428 cases of colon cancer, data from 2410 controls were available for comparative purposes. Participants with Ki-ras mutations were more likely to have proximal rather than distal tumors. Cigarette smoking, use of aspirin and/or NSAIDs, use of vitamin/mineral supplements, and consumption of caffeine were associated with both Ki-ras+ and Ki-ras- tumors; the associations were not confounded by dietary intake or other lifestyle factors. Among men, but not among women, those with low levels of physical activity were more likely to have a tumor with a Ki-ras mutation than one without a Ki-ras mutation. However, among women, those with a larger BMI were more likely to have a Ki-ras mutation in their tumor. Given the limited information available on what causes Ki-ras mutations, the information generated from this study indicates that these factors previously associated with colon cancer work through other disease pathways.     

Age–period–cohort analysis of colorectal cancer in East Anglia, 1971–2005

Background: This study aimed to investigate the incidence trends of colorectal cancer by sex and subsite, in East Anglia from 1971 to 2005. Methods: Using data from the Eastern Cancer Registration and Information Centre, we examined the time trends and the effect of age, period of diagnosis and birth cohort on the incidence of colorectal cancer by sex and subsite. Results: Between 1971 and 2005, 23 875 males and 22 651 females were registered with colorectal cancer in East Anglia. During this period, the increase in the incidence trends was higher among males, more recent periods of diagnosis, and proximal colon. Cohort effects were statistically significant in distal and rectal cancers in males (p < 0.001 and p = 0.05, respectively), and in proximal colon in females (p < 0.001). Period effects were statistically significant across all subsites and both sexes (p < 0.001 for all). Conclusions: Period effects were significant across all subsites for both sexes, whereas cohort effects varied in their significance levels depending on subsite and sex. We suggest that the period effect may be due to an increase in the use of colonoscopy for diagnostic or opportunistic screening, and the cohort effect may be due to aetiological differences in CRC between sexes and subsites.     

Tea and coffee consumption and risk of oral cavity cancer: Results of a large population-based case-control study,the ICARE study

BackgroundResults on the relationship between coffee and tea drinking and the risk of oral cavity cancer are contrasted.The aim of this study was to evaluate the relation between coffee and tea drinking and the risk of oral cavity cancer in France, a high incidence area.Material and methodsWe conducted a population based case–control study with face-to-face interviews and standardized questionnaires (the ICARE study, Investigation of occupational and environmental causes of respiratory cancers). We used data from 689 cases of oral cavity squamous cell carcinoma and 3481 controls. Odds-ratios (ORs) and 95% confidence intervals (95% CI) associated with tea and coffee consumption (quantity, duration, cumulative consumption) were estimated by unconditional logistic regression with adjustment for age, gender, area of residence, education, body mass index, tobacco smoking and alcohol drinking.ResultsWe observed inverse associations between oral cavity cancer and tea or coffee consumption (odds ratio, 0.39; 95% CI 0.21–0.70, for the highest quartile of tea consumption, and 0.60, 95% CI 0.34–1.05, for the highest quartile of coffee consumption). Exclusive tea or coffee consumption was associated with a reduced risk of oral cavity cancer and their joint effect was multiplicative. No differences in risk between men and women or between consumers of tobacco and alcohol and non-consumers were observed. The odds ratios related to the subsites usually included in the oropharynx (soft palate and base of the tongue) did not differ significantly from that observed for the other subsites of the oral cavity.ConclusionsTea and coffee drinking may decrease the risk of oral cavity cancer through antioxidant components which play a role in the repair of cellular damages. These findings need further investigation in prospective studies and the underlying mechanisms in humans remain to be clarified.     

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.     

Dietary Total Antioxidant Capacity and Colorectal Cancer in the Italian EPIC Cohort

Background

Colorectal cancer is the third most common cancer worldwide. Diet has been hypothesized as involved in colorectal cancer etiology, but few studies on the influence of total dietary antioxidant intake on colorectal cancer risk have been performed.

Methods

We investigated the association between colorectal cancer risk and the total antioxidant capacity (TAC) of the diet, and also of intake of selected antioxidants, in 45,194 persons enrolled in 5 centers (Florence, Naples, Ragusa, Turin and Varese) of the European Prospective Investigation into Cancer and Nutrition (EPIC) Italy study. TAC was estimated by the Trolox equivalent antioxidant capacity (TEAC) assay. Hazard ratios (HRs) for developing colorectal cancer, and colon and rectal cancers separately, adjusted for confounders, were estimated for tertiles of TAC by Cox modeling, stratifying by center.

Results

Four hundred thirty-six colorectal cancers were diagnosed over a mean follow-up of 11.28 years. No significant association between dietary TAC and colorectal cancer incidence was found. However for the highest category of TAC compared to the lowest, risk of developing colon cancer was lower (HR: 0.63; 95% CI: 0.44–0.89, P trend: 0.008). By contrast, increasing TAC intake was associated with significantly increasing risks of rectal cancer (2nd tertile HR: 2.09; 95%CI: 1.19–3.66; 3rd tertile 2.48 95%CI: 1.32–4.66; P trend 0.007). Intakes of vitamin C, vitamin E, and ß-carotene were not significantly associated with colorectal cancer risk.

Conclusions

Further prospective studies are needed to confirm the contrasting effects of high total antioxidant intake on risk of colon and rectal cancers.     

Effects of deoxycorticosterone acetate on the electrical properties of rat large intestine: segmental differences

The functional heterogeneity of different segments of the rat large intestine was investigated by means of transepithelial potential difference (PD), short-circuit current (Isc) and transepithelial resistance (Rt) measurements in control rats and after deoxycorticosterone acetate (DOCA) pretreatment. Rt and PD were low in caecum and proximal colon but higher in the distal colon and rectum. Isc was highest in the distal colon, lower in the caecum, proximal colon, and rectum. None of the electrical properties was sensitive to amiloride in control conditions. DOCA increased PD and Isc in the caecum, distal colon and rectum but had no effect in the proximal colon. The increase of the Isc after DOCA in the distal colon and rectum was reached by induction of the amiloride-sensitive Isc associated with reduction of the amiloride-insensitive Isc. The effect of DOCA could be completely prevented by concurrent spironolactone treatment. The results suggest that the epithelia of the proximal parts of the large intestine are "leaky" whereas those of the distal colon and rectum are relatively "tight". It is concluded that there is a marked quantitative and qualitative segmental heterogeneity along the rat large intestine.     

Multiple primary cancers in Denmark 1943-80; influence of possible underreporting and suggested risk factors

The risk of developing a second primary cancer was studied among 171,749 men and 208,192 women who were reported to the Danish Cancer Registry between 1943 and 1980. Only those who survived at least two months were included in the analysis, and more than 1.7 million person-years of observation were accrued. Altogether, 15,084 second primary cancers developed, of which 13,231 were in organs other than the initial or adjacent site [relative risk (RR) = 1.01]. Adjustment for possible underreporting of multiple primary cancers increased the RR to 1.24, which stresses the need for detailed knowledge of registration procedures interpreting results from cancer registries. The unadjusted RR for all sites increased with time, from 0.94 during the first decade of follow-up (excluding the first year) to 1.13 among 30-year survivors, whereas the adjusted RR increased from 1.08 to 1.41. Elevated risks were observed for sites thought to have a common etiology. For example, cancers of smoking-related sites were increased in both directions following cancers of the oral cavity, respiratory tract, and urinary organs. For cancers suspected to have a hormone- or dietary fat-related association, significant reciprocal relationships were seen among cancers of the endometrium, ovary, and colon. Cancer treatment probably is an important factor in second cancer development, even when judged indirectly in the present study. For example, radiotherapy may have been responsible for an elevated risk of subsequent cancers of the thyroid, breast, colon, rectum, bladder, and connective tissue in long-term survivors. Chemotherapy may have increased the risk of subsequent leukemias. Our data further indicate that cancer patients have no general susceptibility to develop new malignant tumors, although high rates may be found for particular sites sharing common risk factors. Conversely, the occurrence of one cancer does not appear to protect against developing a new cancer.     

Risk of second primary cancer associated with pre-diagnostic smoking,alcohol, and obesity in women with keratinocyte carcinoma

Keratinocyte carcinoma (KC), which includes basal-cell carcinoma (BCC) and squamous-cell cancer (SCC), has been associated with an increased risk of second primary cancers (SPCs), although the reason for this increase is unknown. We assessed the effects of smoking, alcohol, and obesity prior to the diagnosis of KC on the development of SPCs, as these are well-established risk factors for multiple cancers and may also contribute to the increased risk of SPCs among those with KC. A total of 15,628 women with self-reported KC were identified in the Nurses’ Health Study. Incident SPCs were assessed throughout the follow-up until June 2012. Cox proportional hazards models were used to calculate the hazard ratios (HRs) of SPC associated with pre-diagnostic smoking, alcohol and body mass index (BMI). We also compared these risk estimates to those for first cancers in all cohort participants. During 193,695 person-years of follow-up, we recorded 2839 SPC cases. Compared with never smokers, current smokers had a significantly elevated risk for SPC overall and specifically for lung, colorectal, and bladder cancers. We also found a positive association between higher BMI and risk for SPC overall as well as for endometrial and bladder SPCs. Women with KC who consumed alcohol ≥30 g/day had a marginally higher risk of SPC compared to non-drinkers. The associations between incident SPC risk among KC cases and smoking, alcohol, and obesity appeared similar to the associations between these risk factors and the incident first primary cancers in the whole cohort. Only in the heavy smoking (≥25 cigarettes/day) category was the HR for SPC after KC (2.34; 95% CI 1.98–2.76) slightly higher than that for the first cancer in the overall cohort (HR 1.86; 95% CI 1.75–1.98, P_{heterogeneity} = 0.01). In conclusion, pre-diagnostic smoking, alcohol and obesity prior to KC diagnosis were associated with risk of SPCs.     

Red and processed meat and colorectal cancer incidence: meta-analysis of prospective studies

Background

The evidence that red and processed meat influences colorectal carcinogenesis was judged convincing in the 2007 World Cancer Research Fund/American Institute of Cancer Research report. Since then, ten prospective studies have published new results. Here we update the evidence from prospective studies and explore whether there is a non-linear association of red and processed meats with colorectal cancer risk.

Methods and Findings

Relevant prospective studies were identified in PubMed until March 2011. For each study, relative risks and 95% confidence intervals (CI) were extracted and pooled with a random-effects model, weighting for the inverse of the variance, in highest versus lowest intake comparison, and dose-response meta-analyses. Red and processed meats intake was associated with increased colorectal cancer risk. The summary relative risk (RR) of colorectal cancer for the highest versus the lowest intake was 1.22 (95% CI  = 1.11−1.34) and the RR for every 100 g/day increase was 1.14 (95% CI  = 1.04−1.24). Non-linear dose-response meta-analyses revealed that colorectal cancer risk increases approximately linearly with increasing intake of red and processed meats up to approximately 140 g/day, where the curve approaches its plateau. The associations were similar for colon and rectal cancer risk. When analyzed separately, colorectal cancer risk was related to intake of fresh red meat (RR _{for 100 g/day increase}  = 1.17, 95% CI  = 1.05−1.31) and processed meat (RR _{for 50 g/day increase}  = 1.18, 95% CI  = 1.10−1.28). Similar results were observed for colon cancer, but for rectal cancer, no significant associations were observed.

Conclusions

High intake of red and processed meat is associated with significant increased risk of colorectal, colon and rectal cancers. The overall evidence of prospective studies supports limiting red and processed meat consumption as one of the dietary recommendations for the prevention of colorectal cancer.     

Multiple primary cancers in Connecticut, 1935-82

Recently, the National Cancer Institute published a comprehensive monograph on multiple primary cancers in Connecticut and Denmark. This paper summarizes some of the observations made on the Connecticut population. Data compiled by the Connecticut Tumor Registry have extended our knowledge about the patterns of multiple primary cancers, especially among long-term survivors of cancer and among patients with relatively rare tumors about which little information currently exists. When compared with the general Connecticut population, cancer patients had a 31 percent (RR = 1.31) increased risk of developing a second cancer and a 23 percent (RR = 1.23) elevated risk of second cancer at a different site from the first. Common environmental exposures seemed responsible for the excess occurrence of many second cancers, particularly those related to cigarette smoking, alcohol consumption, or both. For example, persons with epithelial cancers of the lung, larynx, esophagus, buccal cavity, and pharynx were particularly prone to develop new cancers in the same or contiguous tissue throughout their lifetimes. Cancers of the colon, uterine corpus, breast, and ovary frequently occurred together, suggesting underlying hormonal or dietary influences. Only patients with prostate cancer were at significantly low risk for second cancer development; this might be an artifact of case finding, since advanced age at initial diagnosis was generally associated with an underascertainment of second cancers. Radiotherapy may have caused rectal and other cancer among patients with cancers of the female genital tract, and leukemia among patients with uterine corpus cancer. Chemotherapy with alkylating agents probably contributed to the excess of acute nonlymphocytic leukemia following multiple myeloma or cancers of the breast and ovary. Genetic susceptibility seemed to explain some tumor complexes, such as the multiple occurrences of cutaneous melanoma and the excess of bone cancer following retinoblastoma. Research into multiple cancer syndromes should enhance our understanding of carcinogenic factors and mechanisms and the development of strategies for cancer prevention and control.