Because most colorectal cancer patients survive beyond five years, understanding quality of life among these long-term survivors is essential to providing comprehensive survivor care. We sought to ...identify personal characteristics associated with reported quality of life in colorectal cancer survivors, and sub-groups of survivors potentially vulnerable to very low quality of life.
We assessed quality of life using the Veterans RAND 12-item Health Survey within a population-based sample of 1,021 colorectal cancer survivors in the Seattle Colorectal Cancer Family Registry, approximately 5 years post-diagnosis. In this case-only study, mean physical component summary scores and mental component summary scores were examined with linear regression. To identify survivors with substantially reduced ability to complete daily tasks, logistic regression was used to estimate odds ratios for "very low" summary scores, defined as a score in the lowest decile of the reference US population. All cases were followed for vital status following QoL assessment, and mortality was analyzed with Cox proportional hazards regression.
Lower mean physical component summary score was associated with older age, female sex, obesity, smoking, and diabetes or other co-morbidity; lower mean mental component summary score was associated with younger age and female sex. Higher odds of very low physical component summary score was associated with older age, obesity, less education, smoking, co-morbidities, and later stage at diagnosis; smoking was associated with higher odds of very low mental component summary score. A very low physical component score was associated with higher risk of mortality (hazard ratio (95% confidence interval): 3.97 (2.95-5.34)).
Our results suggest that identifiable sub-groups of survivors are vulnerable to very low physical components of quality of life, decrements that may represent meaningful impairment in completing everyday tasks and are associated with higher risk of death.
Background and Aims Colorectal cancer (CRC) is a heterogeneous disease that can develop via several pathways. Different CRC subtypes, identified based on tumor markers, have been proposed to reflect ...these pathways. We evaluated the significance of these previously proposed classifications to survival. Methods Participants in the population-based Seattle Colon Cancer Family Registry were diagnosed with invasive CRC from 1998 through 2007 in western Washington State (N = 2706), and followed for survival through 2012. Tumor samples were collected from 2050 participants and classified into 5 subtypes based on combinations of tumor markers: type 1 (microsatellite instability MSI–high, CpG island methylator phenotype CIMP –positive, positive for BRAF mutation, negative for KRAS mutation); type 2 (microsatellite stable MSS or MSI-low, CIMP-positive, positive for BRAF mutation, negative for KRAS mutation); type 3 (MSS or MSI low, non-CIMP, negative for BRAF mutation, positive for KRAS mutation); type 4 (MSS or MSI-low, non-CIMP, negative for mutations in BRAF and KRAS ); and type 5 (MSI-high, non-CIMP, negative for mutations in BRAF and KRAS ). Multiple imputation was used to impute tumor markers for those missing data on 1–3 markers. We used Cox regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations of subtypes with disease-specific and overall mortality, adjusting for age, sex, body mass, diagnosis year, and smoking history. Results Compared with participants with type 4 tumors (the most predominant), participants with type 2 tumors had the highest disease-specific mortality (HR = 2.20, 95% CI: 1.47–3.31); subjects with type 3 tumors also had higher disease-specific mortality (HR = 1.32, 95% CI: 1.07–1.63). Subjects with type 5 tumors had the lowest disease-specific mortality (HR = 0.30, 95% CI: 0.14–0.66). Associations with overall mortality were similar to those with disease-specific mortality. Conclusions Based on a large, population-based study, CRC subtypes, defined by proposed etiologic pathways, are associated with marked differences in survival. These findings indicate the clinical importance of studies into the molecular heterogeneity of CRC.
Although high-risk mutations in identified major susceptibility genes (DNA mismatch repair genes and
) account for some familial aggregation of colorectal cancer, their population prevalence and the ...causes of the remaining familial aggregation are not known.
We studied the families of 5,744 colorectal cancer cases (probands) recruited from population cancer registries in the United States, Canada, and Australia and screened probands for mutations in mismatch repair genes and
We conducted modified segregation analyses using the cancer history of first-degree relatives, conditional on the proband's age at diagnosis. We estimated the prevalence of mutations in the identified genes, the prevalence of HR for unidentified major gene mutations, and the variance of the residual polygenic component.
We estimated that 1 in 279 of the population carry mutations in mismatch repair genes (
= 1 in 1,946,
= 1 in 2,841,
= 1 in 758,
= 1 in 714), 1 in 45 carry mutations in
, and 1 in 504 carry mutations associated with an average 31-fold increased risk of colorectal cancer in unidentified major genes. The estimated polygenic variance was reduced by 30% to 50% after allowing for unidentified major genes and decreased from 3.3 for age <40 years to 0.5 for age ≥70 years (equivalent to sibling relative risks of 5.1 to 1.3, respectively).
Unidentified major genes might explain one third to one half of the missing heritability of colorectal cancer.
Our findings could aid gene discovery and development of better colorectal cancer risk prediction models.
.
Exposure to cadmium, a heavy metal present in cigarettes, can be assessed in both urine and blood. Few studies have compared the properties of concurrent measurements of urine cadmium (uCd) and blood ...cadmium (bCd) in relation to the duration and timing of a known exposure. In this study, bCd and uCd were modeled with data from the National Health and Nutrition Examination Survey (1999-2010). Adjusted geometric mean bCd and uCd were estimated from regression results. Each 1% higher geometric mean uCd was associated with 0.50% (95% confidence interval: 0.47%-0.54%; R(2)=0.30) higher bCd. In male never-smokers, bCd was 69% (59%-81%) and uCd was 200% (166%-234%) higher at age ≥70 years versus 20-29 years. Ten pack-years (py) of smoking were associated with 13.7% (10.0%-17.4%) higher bCd and 16.8% (12.6%-21.1%) higher uCd in male smokers. The first year after smoking cessation was associated with 53% (48%-58%) lower bCd and 23% (14%-33%) lower uCd in representative males aged 55 years with 20 py smoking. Smoking in the previous 5 days was associated with 55% (40%-71%) higher bCd and 7% (-3%-18%) higher uCd. Results were similar for women. uCd mainly measures long-term exposure and bCd recent exposure, but with noticeable overlap. Epidemiological studies should base the choice of uCd or bCd on the timing of cadmium exposure relevant to the disease under study.
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.
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).
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.
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.
Background
Initiating screening at an earlier age based on cancer family history is one of the primary recommended strategies for the prevention and detection of early‐onset colorectal cancer ...(EOCRC), but data supporting the effectiveness of this approach are limited. The authors assessed the performance of family history–based guidelines for identifying individuals with EOCRC.
Methods
The authors conducted a population‐based, case‐control study of individuals aged 40 to 49 years with (2473 individuals) and without (772 individuals) incident CRC in the Colon Cancer Family Registry from 1998 through 2007. They estimated the sensitivity and specificity of family history–based criteria jointly recommended by the American Cancer Society, the US Multi‐Society Task Force on CRC, and the American College of Radiology in 2008 for early screening, and the age at which each participant could have been recommended screening initiation if these criteria had been applied.
Results
Family history–based early screening criteria were met by approximately 25% of cases (614 of 2473 cases) and 10% of controls (74 of 772 controls), with a sensitivity of 25% and a specificity of 90% for identifying EOCRC cases aged 40 to 49 years. Among 614 individuals meeting early screening criteria, 98.4% could have been recommended screening initiation at an age younger than the observed age of diagnosis.
Conclusions
Of CRC cases aged 40 to 49 years, 1 in 4 met family history–based early screening criteria, and nearly all cases who met these criteria could have had CRC diagnosed earlier (or possibly even prevented) if earlier screening had been implemented as per family history–based guidelines. Additional strategies are needed to improve the detection and prevention of EOCRC for individuals not meeting family history criteria for early screening.
Data supporting initiating screening at an earlier age based on family history as a strategy for the detection and prevention of early‐onset colorectal cancer (CRC) are limited. In a population‐based, case‐control study of individuals aged 40 to 49 years, the authors report that 1 in 4 meet guideline criteria for earlier screening, and that nearly all of those who meet these criteria could have had CRC diagnosed earlier (or possibly even prevented) if earlier screening had been implemented as per guidelines.
The heterogeneity among colorectal tumors is probably due to differences in developmental pathways and might associate with patient survival times. We studied the relationship among markers of ...different subtypes of colorectal tumors and patient survival.
We pooled data from 7 observational studies, comprising 5010 patients with colorectal cancer. All the studies collected information on microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and mutations in KRAS and BRAF in tumors. Tumors with complete marker data were classified as type 1 (MSI-high, CIMP-positive, with pathogenic mutations in BRAF but not KRAS), type 2 (not MSI-high, CIMP-positive, with pathogenic mutations in BRAF but not KRAS), type 3 (not MSI-high or CIMP, with pathogenic mutations in KRAS but not BRAF), type 4 (not MSI-high or CIMP, no pathogenic mutations in BRAF or KRAS), or type 5 (MSI-high, no CIMP, no pathogenic mutations in BRAF or KRAS). We used Cox regression to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for associations of these subtypes and tumor markers with disease-specific survival (DSS) and overall survival times, adjusting for age, sex, stage at diagnosis, and study population.
Patients with type 2 colorectal tumors had significantly shorter time of DSS than patients with type 4 tumors (HRDSS 1.66; 95% CI 1.33–2.07), regardless of sex, age, or stage at diagnosis. Patients without MSI-high tumors had significantly shorter time of DSS compared with patients with MSI-high tumors (HRDSS 0.42; 95% CI 0.27–0.64), regardless of other tumor markers or stage, or patient sex or age.
In a pooled analysis of data from 7 observational studies of patients with colorectal cancer, we found that tumor subtypes, defined by combinations of 4 common tumor markers, were associated with differences in survival time. Colorectal tumor subtypes might therefore be used in determining patients’ prognoses.
To determine whether cancer risks for carriers and noncarriers from families with a mismatch repair (MMR) gene mutation are increased above the risks of the general population.
We prospectively ...followed a cohort of 446 unaffected carriers of an MMR gene mutation (MLH1, n = 161; MSH2, n = 222; MSH6, n = 47; and PMS2, n = 16) and 1,029 their unaffected relatives who did not carry a mutation every 5 years at recruitment centers of the Colon Cancer Family Registry. For comparison of cancer risk with the general population, we estimated country-, age-, and sex-specific standardized incidence ratios (SIRs) of cancer for carriers and noncarriers.
Over a median follow-up of 5 years, mutation carriers had an increased risk of colorectal cancer (CRC; SIR, 20.48; 95% CI, 11.71 to 33.27; P < .001), endometrial cancer (SIR, 30.62; 95% CI, 11.24 to 66.64; P < .001), ovarian cancer (SIR, 18.81; 95% CI, 3.88 to 54.95; P < .001), renal cancer (SIR, 11.22; 95% CI, 2.31 to 32.79; P < .001), pancreatic cancer (SIR, 10.68; 95% CI, 2.68 to 47.70; P = .001), gastric cancer (SIR, 9.78; 95% CI, 1.18 to 35.30; P = .009), urinary bladder cancer (SIR, 9.51; 95% CI, 1.15 to 34.37; P = .009), and female breast cancer (SIR, 3.95; 95% CI, 1.59 to 8.13; P = .001). We found no evidence of their noncarrier relatives having an increased risk of any cancer, including CRC (SIR, 1.02; 95% CI, 0.33 to 2.39; P = .97).
We confirmed that carriers of an MMR gene mutation were at increased risk of a wide variety of cancers, including some cancers not previously recognized as being a result of MMR mutations, and found no evidence of an increased risk of cancer for their noncarrier relatives.
Previous studies suggest that increased physical activity may lower the risk of breast cancer incidence, but less is known about whether levels of physical activity after breast cancer diagnosis can ...influence survival. We prospectively examined the relation between postdiagnosis recreational physical activity and risk of breast cancer death in women who had a previous invasive breast cancer diagnosed between 1988 and 2001 (at ages 20-79 years). All women completed a questionnaire on recent postdiagnosis physical activity and other lifestyle factors. Among 4,482 women without history of recurrence at the time of completing the questionnaire, 109 died from breast cancer within 6 years of enrollment. Physical activity was expressed as metabolic equivalent task-hours per week (MET-h/wk); hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated using Cox proportional hazards regression. After adjusting for age at diagnosis, stage of disease, state of residence, interval between diagnosis and physical activity assessment, body mass index, menopausal status, hormone therapy use, energy intake, education, family history of breast cancer, and treatment modality compared with women expending <2.8 MET-h/wk in physical activity, women who engaged in greater levels of activity had a significantly lower risk of dying from breast cancer (HR, 0.65; 95% CI, 0.39-1.08 for 2.8-7.9 MET-h/wk; HR, 0.59; 95% CI, 0.35-1.01 for 8.0-20.9 MET-h/wk; and HR, 0.51; 95% CI, 0.29-0.89 for > or =21.0 MET-h/wk; P for trend = 0.05). Results were similar for overall survival (HR, 0.44; 95% CI, 0.32-0.60 for > or =21.0 versus <2.8 MET-h/wk; P for trend <0.001) and were similar regardless of a woman's age, stage of disease, and body mass index. This study provides support for reduced overall mortality and mortality from breast cancer among women who engage in physical activity after breast cancer diagnosis.
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