Survival after hepatic resection of colorectal cancer metastases

BACKGROUND:

Most estimates of short‐ and long‐term survival after hepatic resection of colorectal cancer metastases are derived from surgical case series. For the current report, the authors used Medicare data to investigate operative mortality and long‐term survival in a national sample and examined the factors associated with survival.

METHODS:

Data were analyzed from Medicare enrollees (age ≥65 years) who were admitted to hospital between January 1, 2000 and December 31, 2004 with a primary diagnosis of colorectal cancer with resection. The sample was restricted to patients who subsequently underwent hepatic resection for liver metastases. The Medicare Denominator File was used to determine operative mortality and long‐term survival and the factors that were associated with those outcomes.

RESULTS:

Of the 306,061 Medicare beneficiaries who were diagnosed with colorectal cancer, 3957 patients were identified who underwent hepatic resection for liver metastases. The crude 30‐day and 90‐day mortality rates were 4% and 8.2%, respectively, and the 5‐year survival rate was 25.5%. Advancing age (hazards ratio [HR], 1.83; 95% confidence interval [95% CI], 1.32‐2.53 for age ≥80 years vs ages 65‐69 years), comorbid disease (HR, 1.40; 95% CI, 1.06‐1.85 for Charlson ≥5 vs Charlson 0), and synchronous colon/hepatic resection (HR, 2.46; 95% CI, 1.89‐3.20 for synchronous vs metachronous resection) were associated with worse 90‐day mortality. Similarly, long‐term mortality was associated with age (HR, 1.36; 95% CI, 1.18‐1.56), comorbid disease (HR, 1.51; 95% CI, 1.36‐1.69), and synchronous colon/hepatic resection (HR, 1.37; 95% CI, 1.24‐1.51 for synchronous vs metachronous resection).

CONCLUSIONS:

In this national study, short‐ and long‐term survival was worse than that reported in surgical case series. Subgroups at high risk for worse outcomes include the extreme elderly and those undergoing synchronous colon and hepatic resection. Cancer 2009. © 2009 American Cancer Society.     

Risk of endometrial cancer for women diagnosed with HNPCC‐related colorectal carcinoma

The risk of endometrial cancer (EC) subsequent to a diagnosis of colorectal cancer in women with a germline mutation in a mismatch repair gene [Lynch syndrome or hereditary non‐polyposis colon cancer (HNPCC)] is unknown. We estimated the risk of EC following a diagnosis of colorectal carcinoma (CRC) for women with Lynch syndrome. A retrospective cohort study was performed on women diagnosed with CRC with a germline mutation in a mismatch repair (MMR) gene (Lynch syndrome cases), and women with microsatellite stable (MSS) CRC who were not known to carry a germline mutation (non‐Lynch cases), identified from the Colon Cancer Family Registry. The incidence of EC following CRC was estimated and compared for women with and without Lynch syndrome, using adjusted hazards ratios calculated for time at risk among each group. A total of 112 women with Lynch syndrome and a previous diagnosis of CRC were compared with 908 women without Lynch and with a MSS CRC diagnosis. The estimated 10‐year cumulative risk of EC subsequent to CRC was 23.4% [95% confidence interval (CI): 15–36%] for Lynch syndrome women compared with 1.6% (95% CI: 0.7–3.8%) for non‐Lynch women. After adjusting for ascertainment, age at diagnosis and diagnosis of other cancers, risk of subsequent diagnosis with EC was elevated sixfold in women with Lynch syndrome compared with non‐Lynch women (HR 6.2; 95% CI 2.2–17.3; p = 0.001). Approximately one quarter of women diagnosed with Lynch syndrome‐associated CRC developed EC within 10 years. This supports the sentinel cancer concept and suggests that active and early management is important for these women.     

Risk factors for metachronous adenoma in patients with stage I/II colorectal cancer after radical surgery

BackgroundIt is important to implement a preventive strategy for early detection and endoscopic removal of metachronous adenoma in patients with colorectal cancer (CRC). Here, we retrospectively explored the associated factors of metachronous adenoma in these patients.MethodsThis study recruited 551 patients with stage I and II CRC who underwent radical surgery between January 1, 2012 and July 1, 2017 with postoperative colonoscopic surveillance. Data on clinicopathological characteristics and surveillance colonoscopies were obtained from medical records. Univariate analysis by Kaplan-Meier method and multivariate analysis by Cox proportional hazards model were used to identify the factors associated with metachronous adenoma.ResultsMetachronous adenoma was detected in 110 (20.0%) patients. In these patients, 94.5% (104/110) had metachronous adenoma within 3 years postoperatively. Age, synchronous adenoma, hypertension, tumor stage, and surgical resection were correlated with metachronous adenoma in patients with stage I-II CRC after radical resection (log rank test, P<0.05). Multivariate analyses showed that synchronous adenoma (HR =2.515, 95% CI: 1.691–3.742, P<0.01); stage II (HR =2.066, 95% CI: 1.329–3.210, P<0.01); and left-side colorectal resection (HR =2.207, 95% CI: 1.292–3.772, P<0.01) were independent risk factors.ConclusionsSynchronous adenoma, left-side colorectal resection, and stage II cancer are independent risk factors of metachronous adenoma in patients with previous stage I and II CRC. In patients with risk factors, an enhanced colonoscopic strategy might be needed for early detection and timely endoscopic removal of metachronous adenoma.     

The impact of adjuvant therapy on contralateral breast cancer risk and the prognostic significance of contralateral breast cancer: a population based study in the Netherlands

BACKGROUND: The impact of age and adjuvant therapy on contralateral breast cancer (CBC) risk and prognostic significance of CBC were evaluated. PATIENTS AND METHODS: In 45,229 surgically treated stage I-IIIA patients diagnosed in the Netherlands between 1989 and 2002 CBC risk was quantified using standardised incidence ratios (SIRs), cumulative incidence and Cox regression analysis, adjusted for competing risks. RESULTS: Median follow-up was 5.8 years, in which 624 CBC occurred <6 months after the index cancer (synchronous) and 1,477 thereafter (metachronous). Older age and lobular histology were associated with increased synchronous CBC risk. Standardised incidence ratio (SIR) of CBC was 2.5 (95% confidence interval (95% CI) 2.4-2.7). The SIR of metachronous CBC decreased with index cancer age, from 11.4 (95% CI 8.6-14.8) when <35 to 1.5 (95% CI 1.4-1.7) for > or =60 years. The absolute excess risk of metachronous CBC was 26.8/10,000 person-years. The cumulative incidence increased with 0.4% per year, reaching 5.9% after 15 years. Adjuvant hormonal (Hazard rate ratio (HR) 0.58; 95% CI 0.48-0.69) and chemotherapy (HR 0.73; 95% CI 0.60-0.90) were associated with a markedly decreased CBC risk. A metachronous CBC worsened survival (HR 1.44; 95% CI 1.33-1.56). CONCLUSION: Young breast cancer patients experience high synchronous and metachronous CBC risk. Adjuvant hormonal or chemotherapy considerably reduced the risk of CBC. CBC occurrence adversely affects prognosis, emphasizing the necessity of long-term surveillance directed at early CBC-detection.     

Prediagnostic smoking history, alcohol consumption, and colorectal cancer survival: the Seattle Colon Cancer Family Registry

BACKGROUND:

Smoking and alcohol consumption are associated with an increased risk of developing colorectal cancer. However, it is unclear whether these exposures are associated with survival after colorectal cancer diagnosis.

METHODS:

Men and women diagnosed with incident colorectal cancer between 1998 and 2007 in 13 counties in western Washington State were identified by using the Surveillance, Epidemiology, and End Results cancer registry. Information on smoking history and alcohol consumption was collected by telephone interview. Follow‐up for mortality was completed through linkage to the National Death Index. Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations among smoking, alcohol consumption, and mortality after colorectal cancer diagnosis. Stratified analyses were conducted by sex, age at diagnosis (<50 years, ≥50 years), tumor site (proximal, distal, rectal), stage (I‐II, III‐IV), and microsatellite instability status (stable/low, high).

RESULTS:

Disease‐specific and all‐cause mortality were significantly higher for smokers (HR, 1.30; 95% CI, 1.09‐1.74) compared with never‐smokers (HR, 1.51; 95% CI, 1.24‐1.83). However, this association was most prominent in those with tumors exhibiting high microsatellite instability (HR, 3.83; 95% CI, 1.32‐11.11) and did not extend to those with rectal cancer (HR, 1.08; 95% CI, 0.72‐1.61) or those diagnosed before age 50 years (HR, 0.99; 95% CI, 0.67‐1.48). Alcohol consumption was not associated with disease‐specific or all‐cause mortality, regardless of patient or tumor characteristics.

CONCLUSIONS:

In addition to an association with disease risk, smoking is associated with increased mortality after colorectal cancer diagnosis. This association is especially pronounced for colorectal cancer with high microsatellite instability. Cancer 2011;. © 2011 American Cancer Society.     

High constant incidence of second primary colorectal cancer

Patients who had a colorectal cancer have a 1.5‐ to 2‐fold excess risk of a second colorectal cancer as compared to the general population, the excess being higher at younger age at diagnosis. To further investigate the risk and the age‐relation of the incidence of second primary colorectal cancer, we considered 9,389 first colon and rectal cancers registered in the Vaud Cancer Registry, Switzerland, between 1974 and 2008, and followed‐up to the end of 2008 for a total of 44,113 person‐years. There were 136 second colorectal cancers versus 90.5 expected, corresponding to a standardized incidence ratio (SIR) of 1.5 (95% confidence interval, CI, 1.3–1.8). The SIRs were not heterogeneous between men and women, and in strata of calendar year at diagnosis, duration of follow‐up, and subsite. However, the SIR was 7.5 (95% CI 4.2–12.4) for subjects diagnosed below age 50 and declined thereafter to reach 1.0 (95% CI 0.6–1.6) at age 80 or over. Consequently, the incidence of second primary colorectal cancer was stable, and exceedingly high, around 300–400/100,000 between age 30–39 and 70 or over. This age pattern is consistent with the existence of a single mutational event in a population of highly susceptible individuals.     

Alcohol consumption, type of alcoholic beverage and risk of colorectal cancer at specific subsites

Within the Netherlands Cohort Study on diet and cancer, we investigated associations between total alcohol consumption, specific alcoholic beverage consumption and risk of colorectal cancer (CRC) according to anatomical subsite. Hazard Ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models. Analyses were performed on 2,323 CRC cases, available after 13.3 years of follow-up. Compared to abstaining, alcohol consumption of >/=30.0 g/day ( approximately 3 alcoholic drinks) was positively associated with the risk of CRC (HR: 1.32, 95% CI: 1.06-1.65). Analyses restricted to subjects who reported to have consumed equal amounts of alcohol 5 years before baseline compared to baseline, showed elevated risk estimates for consumers of >/=30.0 g of total alcohol per day as well (HR: 1.53, 95% CI: 1.16-2.01). Suggestive of a subsite-specific effect, cancer risk seemed to increase from proximal colon through rectum; HR: 1.29, 95% CI: 0.85-1.96 for proximal colon cancer, HR: 1.41, 95% CI: 0.94-2.11 for distal colon cancer, HR: 2.07, 95% CI: 1.03-4.18 for rectosigmoid cancer and HR: 1.69, 95% CI: 1.08-2.64 for rectal cancer. No associations were observed between consumption of alcoholic beverages and CRC risk when compared with the nondrinkers of the specific beverage and after adjustment for total alcohol intake. No evidence was found for sex-specific effects of alcohol and alcoholic beverages. In conclusion, our data showed a positive association between alcohol consumption and risk of CRC, which seemed to be mainly explained by the alcoholic content of alcoholic beverages, rather than other constituents. Also, cancer risk may vary according to anatomical subsite.     

Increase in the incidence of synchronous and metachronous peritoneal metastases in patients with colorectal cancer: A nationwide study

Introduction– To investigate the incidence of, factors associated with, and differences between synchronous and metachronous colorectal peritoneal metastases (CPM) in a population-based cohort.Methods– Data from the Netherlands Cancer Registry were used. All patients diagnosed with colorectal cancer (CRC) between 1 January and June 30, 2015 were evaluated for synchronous or metachronous CPM (diagnosis ≤90 or >90 days after surgery for primary CRC), and survival in 2019 (median follow-up 38.4 months).Results– Of 7233 included patients, 409 (5.7%) were diagnosed with synchronous CPM. Factors associated with synchronous CPM were mucinous (OR 2.72 [1.90–3.90]) or signet ring cell (SRC) histology (OR 6.58 [3.66–11.81]), T4 (OR 4.82 [3.68–6.32]), N1 (OR 1.66 [1.20–2.30]), or N2 stage (OR 3.27 [2.36–4.52]), and synchronous systemic metastases (SM) (OR 3.13 [2.37–4.14]). After surgery for primary CRC, 326 patients developed metachronous CPM after a median time of 14.7 months (3-year cumulative incidence: 5.5%). Factors associated with metachronous CPM were younger age (HR 1.63 [1.10–2.42]), mucinous (HR 1.84 [1.20–2.82]) or SRC histology (HR 2.43 [1.11–5.32]), T4 (HR 2.77 [2.07–3.70]), N1 (HR 2.90 [2.18–3.85]), N2 (HR 3.19 [2.26–4.50]), and synchronous SM (HR 1.95 [1.43–2.66]).Conclusion– This population-based study found the highest incidence of CPM currently reported in literature and a strong association between the presence of synchronous SM and both synchronous and metachronous CPM. These findings may contribute to a tailored approach in the follow-up after primary CRC surgery and guide future clinical trials investigating new strategies regarding risk-reduction or early detection of metachronous CPM.     

Predictors of metachronous colorectal neoplasms in sporadic adenoma patients

Our objective was to assess the overall risk of subsequent colorectal neoplasms (cancer or adenoma) in relation with the various characteristics of the index lesion in a cohort of patients who underwent endoscopic polypectomies of colorectal adenomas. A total of 1086 patients with adenomas of the large bowel were reported between 1979 and 1999 at the National Cancer Institute of Milan during a screening program for colorectal carcinoma. Data on patients who had colonoscopic examinations and treatments were collected prospectively. The relation between colorectal cancer (CRC) and adenoma features was assessed by computing the hazard ratio (HR) values and corresponding confidence intervals (95% CI) according to Cox proportional hazard models. Of the 1086 eligible patients (487 females, 579 males), 736 had single adenomas (67.7%) and 350 had multiple adenomas (32.3%). Histologic examination revealed 772 cases of tubular adenoma (73%), 205 cases of tubulovillous adenoma and 80 cases of villous adenoma (7.5%). Severe dysplasia was found in 3.3% of the cases. During the 11393 person-years of follow-up, with an average time of surveillance of 10.5 years, colorectal carcinomas developed in 10 patients (0.8%) and a new adenoma in 323 patients (29%). Multivariate analysis showed that male gender (HR 1.6; 95% CI 1.3-2.0), multiple polyps (HR 1.6; 95% CI 1.3-2.0), polyps larger than 2 cm (HR 1.5; 95% CI 1.1-2.1), tubulovillous and villous histology (HR 1.3; 95% CI 1.0-1.6 and HR 1.8; 95% CI 1.2-2.6, respectively) at index polypectomy were statistically significant risk factors for developing metachronous adenomatous polyps. The standardized incidence rates (SIR) for CRC was 0.52 (95% CI 0.25-0.95). The SIR was increased in subjects with severe dysplasia (2.8; 95% CI 0.34-1.02). Some features of large bowel adenomas are strongly correlated with an increased risk of metachronous adenomas and colorectal cancer. However, the endoscopic polypectomy is able to reduce by 50% the incidence of CRC in patients with large bowel adenomas.     

Meat subtypes and colorectal cancer risk: A pooled analysis of 6 cohort studies in Japan

Red meat and processed meat have been suggested to increase risk of colorectal cancer (CRC), especially colon cancer. However, it remains unclear whether these associations differ according to meat subtypes or colon subsites. The present study addressed this issue by undertaking a pooled analysis of large population‐based cohort studies in Japan: 5 studies comprising 232 403 participants (5694 CRC cases) for analysis based on frequency of meat intake, and 2 studies comprising 123 635 participants (3550 CRC cases) for analysis based on intake quantity. Study‐specific hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using the Cox proportional hazards model and then pooled using the random effect model. Comparing the highest vs lowest quartile, beef intake was associated with an increased risk of colon cancer in women (pooled HR 1.20; 95% CI, 1.01‐1.44) and distal colon cancer (DCC) risk in men (pooled HR 1.30; 95% CI, 1.05‐1.61). Frequent intake of pork was associated with an increased risk of distal colon cancer in women (pooled HR 1.44; 95% CI, 1.10‐1.87) for “3 times/wk or more” vs “less than 1 time/wk”. Frequent intake of processed red meat was associated with an increased risk of colon cancer in women (pooled HR 1.39; 95% CI, 0.97‐2.00; P trend = .04) for “almost every day” vs “less than 1 time/wk”. No association was observed for chicken consumption. The present findings support that intake of beef, pork (women only), and processed red meat (women only) might be associated with a higher risk of colon (distal colon) cancer in Japanese.     

Family history of hormonal cancers and colorectal cancer risk: A case‐control study conducted in Ontario

Aggregation of cancers among families with highly penetrant genetic mutations such as hereditary nonpolyposis colorectal cancer is well‐described. However, there is a paucity of data regarding familial aggregation of hormonal cancers (cancers of the breast, endometrial, ovarian and prostate) and colorectal cancer (CRC) in the general population. We investigated the association between having a first‐degree family history of breast, endometrial, ovarian, or prostate cancer and CRC risk. Population‐based CRC cases and controls were recruited by the Ontario Familial Colorectal Cancer Registry (OFCCR). Logistic regression was conducted to obtain odds ratio (OR) estimates and 95% confidence intervals (95% CIs). First‐degree family history of breast cancer was associated with a modest, borderline statistically significant increased CRC risk (age‐, sex‐adjusted OR = 1.2, 95% CI = 1.0, 1.5). The magnitude of CRC risk was greatest if more than one first‐degree kin had breast cancer (age‐, sex‐adjusted OR = 1.7, 95% CI = 1.0, 2.0), as well as if the kin was diagnosed at >50 years of age (age‐, sex‐adjusted OR = 1.4, 95% CI = 1.1, 1.8). Family history of ovarian cancer was associated with reduced CRC risk (multivariate‐adjusted OR = 0.6, 95% CI = 0.3, 1.0). Although statistically significant increases in CRC risk were observed in the age‐, sex‐adjusted OR estimates for family history of endometrial and prostate cancers, the associations were no longer significant after multivariate‐adjustment. In conclusion, individuals with a first‐degree kin with breast cancer may have a modest increased risk for CRC compared to individuals without. © 2009 UICC     

Educational level and risk of colorectal cancer in EPIC with specific reference to tumor location

Existing evidence is inconclusive on whether socioeconomic status (SES) and educational inequalities influence colorectal cancer (CRC) risk, and whether low or high SES/educational level is associated with developing CRC. The aim of our study was to investigate the relationship between educational level and CRC. We studied data from 400,510 participants in the EPIC (European Prospective Investigation into Cancer and Nutrition) study, of whom 2,447 developed CRC (colon: 1,551, rectum: 896, mean follow-up 8.3 years). Cox proportional hazard regression analysis stratified by age, gender and center, and adjusted for potential confounders were used to estimate hazard ratios (HR) and 95% confidence intervals (95%CI). Relative indices of inequality (RII) for education were estimated using Cox regression models. We conducted separate analyses for tumor location, gender and geographical region. Compared with participants with college/university education, participants with vocational secondary education or less had a nonsignificantly lower risk of developing CRC. When further stratified for tumor location, adjusted risk estimates for the proximal colon were statistically significant for primary education or less (HR 0.73, 95%CI 0.57-0.94) and for vocational secondary education (HR 0.76, 95%CI 0.58-0.98). The inverse association between low education and CRC risk was particularly found in women and Southern Europe. These associations were statistically significant for CRC, for colon cancer and for proximal colon cancer. In conclusion, CRC risk, especially in the proximal colon, is lower in subjects with a lower educational level compared to those with a higher educational level. This association is most pronounced in women and Southern Europe.     

Type 2 diabetes and colorectal cancer survival: The multiethnic cohort

This analysis examined type 2 diabetes (T2D) as a predictor of colorectal cancer (CRC) survival within the Multiethnic Cohort Study. Registry linkages in Hawaii and California identified 5,284 incident CRC cases. After exclusion of cases with pre‐existing cancer diagnosis within 1 year and systemic disease, the analytic dataset had 3,913 cases with 1,800 all‐cause and 678 CRC‐specific deaths after a mean follow‐up of 9.3 ± 5.2 years. Among CRC cases, 707 were diagnosed with T2D 8.9 ± 5.3 years before CRC. Cox regression with age as time metric was applied to estimate hazard ratios (HR) and 95% confidence intervals (CI) for T2D status as predictor of CRC‐specific and all‐cause survival while adjusting for known confounders. Overall, CRC‐specific survival was not associated with pre‐existing T2D (HR = 0.84; 95% CI = 0.67–1.07). However, a significant interaction was seen for comorbidity (p_interaction = 0.03) with better survival among those without pre‐existing conditions (HR = 0.49; 95% CI = 0.25–0.96) while no association was seen in patients with comorbid conditions. All‐cause mortality was also not related to pre‐existing T2D (HR = 1.11; 95% CI = 0.98–1.27), but significantly elevated for individuals with T2D reporting comorbid conditions (HR = 1.36; 95% CI = 1.19–1.56). Stratification by T2D duration suggested higher CRC‐specific and all‐cause mortality among participants with a T2D history of ≥10 than <10 years. The findings were consistent across sex and ethnic subgroups. In contrast to previous reports, pre‐existing T2D had no influence on disease‐specific and all‐cause survival among CRC patients. Only participants with additional comorbidity and possibly those with long T2D duration experienced higher mortality related to T2D.     

Dietary glycemic index and glycemic load and risk of colorectal cancer: results from the EPIC‐Italy study

A carbohydrate‐rich diet, resulting in high blood glucose and insulin, has been hypothesized as involved in colorectal cancer etiology. We investigated dietary glycemic index (GI) and glycemic load (GL), in relation to colorectal cancer, in the prospectively recruited EPIC‐Italy cohort. After a median 11.7 years, 421 colorectal cancers were diagnosed among 47,749 recruited adults. GI and GL were estimated from validated food frequency questionnaires. Multivariable Cox modeling estimated hazard ratios (HRs) for associations between colorectal cancer and intakes of total, high GI and low GI carbohydrate and GI and GL. The adjusted HR of colorectal cancer for highest versus lowest GI quartile was 1.35; 95% confidence interval (CI) 1.03–1.78; p trend 0.031. Increasing high GI carbohydrate intake was also significantly associated with increasing colorectal cancer risk (HR 1.45; 95% CI 1.04–2.03; p trend 0.034), whereas increasing low GI carbohydrate was associated with reducing risk (HR 0.73; 95% CI 0.54–0.98; p trend 0.033). High dietary GI and high GI carbohydrate were associated with increased risks of cancer at all colon sites (HR 1.37; 95% CI 1.00–1.88, HR 1.80; 95% CI 1.22–2.65, respectively), whereas high GI carbohydrate and high GL were associated with increased risk of proximal colon cancer (HR 1.94; 95% CI 1.18–3.16, HR 2.01; 95% CI 1.08–3.74, respectively). After stratification for waist‐to‐hip ratio (WHR), cancer was significantly associated with GI, and high GI carbohydrate, in those with high WHR. These findings suggest that high dietary GI and high carbohydrate intake from high GI foods are associated with increased risk of colorectal cancer.     

Family history and survival after colorectal cancer diagnosis

BACKGROUND

A history of colorectal cancer in a first‐degree relative is a recognized risk factor for developing this malignancy. The influence of a family history of colorectal cancer on survival after a diagnosis of colorectal cancer was examined in a large cohort of women.

METHODS

We analyzed data from 1001 women diagnosed with colorectal cancer while participating in a prospective cohort study. Data on family history were obtained before cancer diagnosis. We computed Cox proportional hazards for cancer‐specific and overall mortality according to a family history of colorectal cancer, adjusting for other predictors for survival.

RESULTS

Before diagnosis, 16% of colorectal patients reported a history of colorectal cancer in a first‐degree relative. Patients with a history of colorectal cancer in 1 or more first‐degree relatives experienced an adjusted hazard ratio (HR) for overall mortality of 1.32 (95% confidence interval [CI], 1.01–1.72) and colorectal cancer‐specific mortality of 1.38 (95% CI, 1.02–1.86) when compared with those without a family history. Moreover, patients with 2 or more affected relatives had an HR for overall mortality of 2.07 (95% CI, 1.14–3.76) and cancer‐specific mortality of 2.19 (95% CI, 1.10–4.38). The significant deleterious effect of family history was limited to patients with advanced disease at presentation and cancers originating in the colon.

CONCLUSIONS

Among women with colorectal cancer, a history of colorectal cancer in a first‐degree relative was associated with a significant decrease in survival. Additional study is needed to validate these findings and determine whether specific germline polymorphisms correlate with clinical outcomes. Cancer 2008. © 2008 American Cancer Society.     

Meat subtypes and their association with colorectal cancer: Systematic review and meta‐analysis

Associations between specific red meat subtypes and risk of colorectal cancer (CRC) have been investigated in a number of epidemiological studies. However, no publication to date has summarised the overall epidemiological evidence. We conducted a systematic review and meta‐analysis of prospective studies (cohort, nested case‐control or case‐cohort studies), which reported relative risk (RR) estimates and 95% confidence intervals (CI) for the association between intake of meat subtypes with colorectal, colon or rectal cancer or colorectal adenoma risk. PubMed and ISI Web of Science were searched up until August 1, 2014. Nineteen studies examined meat subtypes (5 beef, 5 pork, 2 lamb, 1 veal and 19 poultry) and associations with colorectal, colon or rectal cancer risk and 4 studies examined associations with adenoma risk (1 beef and 4 poultry). Comparing highest versus lowest intake, beef consumption was associated with an increased risk of CRC (RR = 1.11, 95% CI = 1.01 to 1.22) and colon cancer (RR = 1.24, 95% CI = 1.07 to 1.44), but no association was found with rectal cancer (RR = 0.95, 95% CI = 0.78 to 1.16). Higher consumption of lamb was also associated with increased risk of CRC (RR = 1.24, 95% CI = 1.08 to 1.44). No association was observed for pork (RR = 1.07, 95% CI = 0.90 to 1.27), but some between study heterogeneity was observed. No association was observed for poultry consumption and risk of colorectal adenomas or cancer. This meta‐analysis suggests that red meat subtypes differ in their association with CRC and its sub sites. Further analysis of data from prospective cohort studies is warranted, especially regarding the role of pork.     

Predictors of survival after hepatic resection among patients with colorectal liver metastasis

Studies suggest improved survival following resection of colorectal cancer liver metastases (CLMs). We investigated predictors of survival among patients with CLM who underwent hepatic resection using the SEER-Medicare database to identify patients >/=65 years diagnosed with CLM, 1991-2003, who underwent hepatectomy. Cox proportional hazards models were used to identify factors associated with survival after hepatectomy. Of 923 patients with CLM who underwent hepatectomy, 514 were stages I-III and developed CLM>6 months after diagnosis (metachronous), and 409 were stage IV with CLM at diagnosis (synchronous). From the date of hepatectomy, 5 year survival was 22%; younger age, being married, female gender, surgery in an NCI-designated cancer centre, fewer comorbidities, fewer positive lymph nodes, and lower grade were associated with improved survival. Both 5-fluorouracil (5FU)-based chemotherapy and hepatic arterial infusion (HAI) of floxuridine-based chemotherapy following hepatectomy improved survival (HR=0.62, 95% CI: 0.50-0.78; HR=0.51, 95% CI: 0.28-0.97, respectively) in the synchronous, but not metachronous, group. The HR for overall mortality was higher in hospitals with a high vs low procedure volume (0.75, 95% CI: 0.58-0.94). A substantial subgroup of patients with CLM who undergo hepatectomy experiences long-term survival. High hospital procedure volume and use of 5FU-based or HAI-based chemotherapy after resection were associated with improved prognosis.     

Genetic variants in C‐type lectin genes are associated with colorectal cancer susceptibility and clinical outcome

Inflammatory responses play a vital role at different stages of colorectal carcinogenesis. C‐type lectins mediate inflammatory/immune responses and participate in immune escape of pathogens and tumors. Our study aimed to evaluate the correlation between polymorphisms in three C‐type lectin genes, CD209, MBL2 and REG4, and colorectal cancer (CRC) risk and clinical outcome. We genotyped 15 potentially functional single nucleotide polymorphisms (SNPs) and assessed their associations with CRC risk in a case‐control study of 1353 CRC cases and 767 healthy controls from the Czech Republic. We also analyzed these SNPs in relation to overall and event‐free survival in 414 patients. Two CD209 SNPs were associated with CRC risk after adjustment for multiple comparison. Minor allele carriers of the promoter SNP rs2287886 had an increased risk of CRC (OR 1.30, 95% CI 1.08–1.56), while minor allele carriers of the 3′UTR SNP, rs7248637, had a decreased risk (OR 0.74, 95% CI 0.60–0.91). Multivariate survival analyses, including age, gender, TNM stage and grade, showed that patients without distant metastasis at the time of diagnosis and carrying the rs2994809 T allele had a decreased overall and event‐free survival (HR 2.11, 95% CI 1.20–3.72 and HR 2.00, 95% CI 1.18–3.39, respectively). We show that SNPs in CD209 may affect CRC risk, while a SNP in REG4 may be a useful marker for CRC progression.     

Second primary cancer among 217702 colorectal cancer survivors: An analysis of national German cancer registry data

With improvements in survival after colorectal cancer (CRC), more survivors are at risk of developing a second cancer, particularly in younger populations where CRC incidence is increasing. We estimated the incidence of second primary cancer (SPC) in CRC survivors and its potential risk factors. We identified CRC cases diagnosed between 1990 and 2011 and SPCs until 2013 from nine German cancer registries. Standardized incidence ratios (SIR) and absolute excess risk (AER) per 10 000 person-years were calculated and were stratified by index site: colon cancer (CC) and rectal cancer (RC), age and sex. Cox regression assessed potential SPC risk factors, including primary tumor-related therapy considering death as a competing risk. We included 217 202 primary CRC cases. SPC occurred in 18 751 CRC survivors (8.6%; median age: 69 years). Risk of cancer was significantly higher in CRC survivors than in the general population (SIR males 1.14, 95% confidence interval [CI] 1.12-1.17, AER = 24.7; SIR females 1.20, 95% CI 1.17-1.23, AER = 22.8). Increased risks of SPCs were observed for the digestive system, urinary system and female and male reproductive organs. CRC incidence increased in younger persons (<50 years) and SPC incidence was 4-fold in this group (SIR males 4.51, 95% CI 4.04-5.01, AER = 64.2; SIR females 4.03, 95% CI 3.62-4.48, AER = 77.0). Primary tumor-related factors associated with SPC risk were right-sided cancer and smaller primary tumor size. Treatment and risk of SPC differed for CC (no effect) and RC (lower risk after chemotherapy). CRC survivors have excess risk of developing SPC, with particular characteristics that could guide targeted surveillance.