Screening strategies for colorectal cancer among patients with nonalcoholic fatty liver disease and family history

Patients with nonalcoholic fatty liver disease (NAFLD) and family history of colorectal cancer (CRC) are at higher risks but how they should be screened remains uncertain. Hence, we evaluated the cost‐effectiveness of CRC screening among patients with NAFLD and family history by different strategies. A hypothetical population of 100,000 subjects aged 40–75 years receive: (i) yearly fecal immunochemical test (FIT) at 50 years; (ii) flexible sigmoidoscopy (FS) every 5 years at 50 years; (iii) colonoscopy 10 yearly at 50 years; (iv) colonoscopy 10 yearly at 50 years among those with family history/NAFLD and yearly FIT at 50 years among those without; (v) colonoscopy 10 yearly at 40 years among those with family history/NAFLD and yearly FIT at 50 years among those without and (vi) colonoscopy 10 yearly at 40 years among those with family history/NAFLD and colonoscopy 10 yearly at 50 years among those without. The incremental cost‐effectiveness ratio (ICER) was studied by Markov modeling. It was found that colonoscopy, FS and FIT reduced incidence of CRC by 49.5, 26.3 and 23.6%, respectively. Using strategies 4, 5 and 6, the corresponding reduction in CRC incidence was 29.9, 30.9 and 69.3% for family history, and 33.2, 34.7 and 69.8% for NAFLD. Compared with no screening, strategies 4 (US$1,018/life‐year saved) and 5 (US$7,485) for family history offered the lowest ICER, whilst strategy 4 (US$5,877) for NAFLD was the most cost‐effective. These findings were robust when assessed with a wide range of deterministic sensitivity analyses around the base case. These indicated that screening patients with family history or NAFLD by colonoscopy at 50 years was economically favorable.     

Association between physical activity and mortality in colorectal cancer: A meta‐analysis of prospective cohort studies

Several prospective cohort studies have examined the association between prediagnosis and/or postdiagnosis physical activity (PA) on colorectal cancer outcomes and reported conflicting results. To quantitatively assess this association, we have conducted a meta‐analysis of prospective studies. Databases and reference lists of relevant studies were searched using MEDLINE and EMBASE up to January 2013. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using random‐effects models. For this meta‐analysis, a total of seven prospective cohort studies were included. The analysis included 5,299 patients for prediagnosis PA and 6,348 patients for postdiagnosis PA, followed up over a period ranging from 3.8 to 11.9 years. The analyses showed that patients who participated in any amount of PA before diagnosis had a RR of 0.75 (95% CI: 0.65–0.87, p < 0.001) for colorectal cancer‐specific mortality compared to patients who did not participate in any PA. Those who participated in high PA before diagnosis (vs. low PA) had a RR of 0.70 (95% CI: 0.56–0.87, p = 0.002). Similarly, patients who participated in any PA after diagnosis had a RR of 0.74 (95% CI: 0.58–0.95, p = 0.02) for colorectal cancer‐specific mortality compared to patients who did not participate in any PA. Those who participated in high PA after diagnosis (vs. low PA) had a RR of 0.65 (95% CI: 0.47–0.92, p = 0.01). Similar inverse associations of prediagnosis or postdiagnosis PA were found for all‐cause mortality. In conclusion, both prediagnosis and postdiagnosis PA were associated with reduced colorectal cancer‐specific mortality and all‐cause mortality.     

Lung cancer in never smokers in the UK Million Women Study

To assess directly the effects of various risk factors on lung cancer incidence among never smokers, large prospective studies are needed. In a cohort of 1.2 million UK women without prior cancer, half (634,039) reported that they had never smoked. Mean age at recruitment was 55 (SD5) years, and during 14 (SD3) years of follow‐up, 0.2% (1,469) of these never smokers developed lung cancer. Cox regression was used to estimate relative risks (RRs) of lung cancer for 34 potential risk factors, of which 31 were nonsignificant (p > 0.05). The remaining three risk factors were associated with a significantly increased incidence of lung cancer in never smokers: non‐white vs. white ethnicity (RR = 2.34, 95% CI 1.55–3.52, p < 0.001), asthma requiring treatment vs. not (RR = 1.32, 1.10–1.58, p = 0.003) and taller stature (height ≥ 165 cm vs. <160 cm: RR = 1.16, 1.03–1.32, p = 0.02). There was little association with other sociodemographic, anthropometric or hormonal factors, or with dietary intakes of meat, fish, fruit, vegetables and fiber. The findings were not materially affected by restricting the analyses to adenocarcinomas, the most common histological type among never smokers.     

Cost‐effectiveness of digital mammography screening before the age of 50 in The Netherlands

In the Netherlands, routine mammography screening starts at age 50. This starting age may have to be reconsidered because of the increasing breast cancer incidence among women aged 40 to 49 and the recent implementation of digital mammography. We assessed the cost‐effectiveness of digital mammography screening that starts between age 40 and 49, using a microsimulation model. Women were screened before age 50, in addition to the current programme (biennial 50–74). Screening strategies varied in starting age (between 40 and 50) and frequency (annual or biennial). The numbers of breast cancers diagnosed, life‐years gained (LYG) and breast cancer deaths averted were predicted and incremental cost‐effectiveness ratios (ICERs) were calculated to compare screening scenarios. Biennial screening from age 50 to 74 (current strategy) was estimated to gain 157 life years per 1,000 women with lifelong follow‐up, compared to a situation without screening, and cost €3,376/LYG (3.5% discounted). Additional screening increased the number of LYG, compared to no screening, ranging from 168 to 242. The costs to generate one additional LYG (i.e., ICER), comparing a screening strategy to the less intensive alternative, were estimated at €5,329 (biennial 48–74 vs. current strategy), €7,628 (biennial 45–74 vs. biennial 48–74), €10,826 (biennial 40–74 vs. biennial 45–74) and €18,759 (annual 40–49 + biennial 50–74 vs. biennial 40–74). Other strategies (49 + biennial 50–74 and annual 45–49 + biennial 50–74) resulted in less favourable ICERs. These findings show that extending the Dutch screening programme by screening between age 40 and 49 is cost‐effective, particularly for biennial strategies.     

Cost-effectiveness of population-based screening for colorectal cancer: a comparison of guaiac-based faecal occult blood testing, faecal immunochemical testing and flexible sigmoidoscopy

Background:

Several colorectal cancer-screening tests are available, but it is uncertain which provides the best balance of risks and benefits within a screening programme. We evaluated cost-effectiveness of a population-based screening programme in Ireland based on (i) biennial guaiac-based faecal occult blood testing (gFOBT) at ages 55–74, with reflex faecal immunochemical testing (FIT); (ii) biennial FIT at ages 55–74; and (iii) once-only flexible sigmoidoscopy (FSIG) at age 60.

Methods:

A state-transition model was used to estimate costs and outcomes for each screening scenario vs no screening. A third party payer perspective was adopted. Probabilistic sensitivity analyses were undertaken.

Results:

All scenarios would be considered highly cost-effective compared with no screening. The lowest incremental cost-effectiveness ratio (ICER vs no screening €589 per quality-adjusted life-year (QALY) gained) was found for FSIG, followed by FIT (€1696) and gFOBT (€4428); gFOBT was dominated. Compared with FSIG, FIT was associated with greater gains in QALYs and reductions in lifetime cancer incidence and mortality, but was more costly, required considerably more colonoscopies and resulted in more complications. Results were robust to variations in parameter estimates.

Conclusion:

Population-based screening based on FIT is expected to result in greater health gains than a policy of gFOBT (with reflex FIT) or once-only FSIG, but would require significantly more colonoscopy resources and result in more individuals experiencing adverse effects. Weighing these advantages and disadvantages presents a considerable challenge to policy makers.     

Assessing individual risk for high‐risk colorectal adenoma at first‐time screening colonoscopy

Assessing risk of colorectal adenoma at first‐time colonoscopy that are of higher likelihood of developing advanced neoplasia during surveillance could help tailor first‐line colorectal cancer screening. We developed prediction models for high‐risk colorectal adenoma (at least one adenoma ≥1 cm, or with advanced histology, or ≥3 adenomas) among 4,881 asymptomatic white men and 17,970 women who underwent colonoscopy as their first‐time screening for colorectal cancer in two prospective US studies using logistic regressions. C‐statistics and Hosmer–Lemeshow tests were used to evaluate discrimination and calibration. Ten‐fold cross‐validation was used for internal validation. A total of 330 (6.7%) men and 678 (3.8%) women were diagnosed with high‐risk adenoma at first‐time screening colonoscopy. The model for men included age, family history of colorectal cancer, BMI, smoking, sitting watching TV/VCR, regular aspirin/NSAID use, physical activity, and a joint term of multivitamin and alcohol. For women, the model included age, family history of colorectal cancer, BMI, smoking, alcohol, beef/pork/lamb as main dish, regular aspirin/NSAID, calcium, and oral contraceptive use. The C‐statistic of the model for men was 0.67 and 0.60 for women (0.64 and 0.57 in cross‐validation). Both models calibrated well. The predicted risk of high‐risk adenoma for men in the top decile was 15.4% vs. 1.8% for men in the bottom decile (Odds Ratio [OR] = 9.41), and 6.6% vs. 2.1% for women (OR = 3.48). In summary, we developed and internally validated an absolute risk assessment tool for high‐risk colorectal adenoma among the US population that may provide guidance for first‐time colorectal cancer screening.     

Colorectal cancer prevention by an optimized colonoscopy protocol in routine practice

We conducted a retrospective cohort study to investigate the colorectal cancer (CRC) incidence and mortality prevention achievable in clinical practice with an optimized colonoscopy protocol targeting near‐complete polyp clearance. The protocol consisted of: (i) telephonic reinforcement of bowel preparation instructions; (ii) active inspection for polyps throughout insertion and circumferential withdrawal; and (iii) timely updating of the protocol and documentation to incorporate the latest guidelines. Of 17,312 patients provided screening colonoscopies by 59 endoscopists in South Carolina, USA from September 2001 through December 2008, 997 were excluded using accepted exclusion criteria. Data on 16,315 patients were merged with the South Carolina Central Cancer Registry and Vital Records Registry data from January 1996 to December 2009 to identify incident CRC cases and deaths, incident lung cancers and brain cancer deaths (comparison control cancers). The standardized incidence ratios (SIR) and standardized mortality ratios (SMR) relative to South Carolina and US SEER‐18 population rates were calculated. Over 78,375 person‐years of observation, 18 patients developed CRC versus 104.11 expected for an SIR of 0.17, or 83% CRC protection, the rates being 68% and 91%, respectively among the adenoma‐ and adenoma‐free subgroups (all p < 0.001). Restricting the cohort to ensure minimum 5‐year follow‐up (mean follow‐up 6.64 years) did not change the results. The CRC mortality reduction was 89% (p < 0.001; four CRC deaths vs. 35.95 expected). The lung cancer SIR was 0.96 (p = 0.67), and brain cancer SMR was 0.92 (p = 0.35). Over 80% reduction in CRC incidence and mortality is achievable in routine practice by implementing key colonoscopy principles targeting near‐complete polyp clearance.     

Circulating 25‐hydroxyvitamin D,vitamin D‐binding protein and risk of prostate cancer

We recently reported a significant positive association between 25‐hydroxyvitamin D [25(OH)D], the accepted biomarker of vitamin D status, and prostate cancer risk. To further elucidate this association, we examined the influence of vitamin D‐binding protein (DBP), the primary transporter of vitamin D compounds in the circulation. Prediagnostic serum concentrations of DBP were assayed for 950 cases and 964 matched controls with existing 25(OH)D measurements within the Alpha‐Tocopherol, Beta‐Carotene Cancer Prevention Study of Finnish men. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), and statistical tests were two sided. Serum DBP modified the association between serum 25(OH)D and prostate cancer, with higher risk for elevated 25(OH)D levels observed primarily among men having DBP concentrations above the median (OR = 1.81, 95% CI: 1.18–2.79 for highest vs. lowest quintile, p‐trend = 0.001) compared to those with DBP below the median (OR = 1.22, 95% CI: 0.81–1.84, p‐trend 0.97; p‐interaction = 0.04). Serum DBP was not associated with prostate cancer risk overall (OR = 0.96, 95% CI: 0.70–1.33 for highest vs. lowest quintile); however, high serum DBP was associated with significantly decreased risk of prostate cancer in men with lower (<median) 25(OH)D concentrations (OR = 0.59, 95% CI: 0.38–0.90 for highest vs. lowest quintile, p‐trend = 0.003) and increased risk in men with higher 25(OH)D concentrations (OR = 1.47, 95% CI: 0.98–2.20, p‐trend 0.10, p‐interaction = 0.02). Our data suggest that the primary vitamin D carrier protein, DBP, modulates the impact of vitamin D status on prostate cancer.     

Body size across the life course and prostate cancer in the Health Professionals Follow‐up Study

Current evidence of an association between body size and prostate cancer is conflicting, possibly due to differential effects of body size across the lifespan and the heterogeneity of the disease. We therefore examined childhood and adult body size in relation to total incident prostate cancer and prognostic subtypes in a prospective cohort of 47,491 US men in the Health Professionals Follow‐up Study. We assessed adult height, body mass index (BMI) in early and middle‐to‐late adulthood, adult waist circumference, and body shape at age 10. With follow‐up from 1986 to 2010, we estimated the relative risk (RR) of prostate cancer using Cox proportional hazards models. We identified 6,183 incident cases. Tallness was associated with increased risk of advanced‐stage tumors, particularly fatal disease (RR = 1.66, 95% CI 1.23–2.23, highest vs. lowest quintile, p_trend < 0.001). High BMI at age 21 was inversely associated with total prostate cancer (RR = 0.89, 95% CI 0.80–0.98, BMI ≥26 vs. 20–21.9, p_trend = 0.01) and with fatal and advanced disease. The association for late adult BMI differed by age (p_interaction < 0.001); high BMI was inversely associated with total prostate cancer (RR = 0.64, 95% CI 0.51–0.78, BMI ≥30 vs. 21–22.9, p_trend<0.001) and with non‐advanced and less aggressive tumors among men ≤65 years, whereas no association was seen among men >65 years. Adult waist circumference was weakly inversely associated with less aggressive disease. Childhood obesity was unclearly related to risk. Our study confirms tall men to be at increased risk of fatal and advanced prostate cancer. The influence of adiposity varies by prognostic disease subtype and by age. The relationship between body size and prostate cancer is complex. Body size changes progressively throughout life and consequent effects on prostate cancer risk may be associated with related changes in hormonal and metabolic pathways. This large prospective study examined potential associations between the risk of various prostate cancer subtypes and multiple anthropometric measures at different ages in men. Tallness was confirmed to be associated with an elevated risk of advanced prostate cancer, particularly fatal disease. The extent to which body weight influenced risk varied according to factors such as age and disease subtype.     

Seasonal variations do not affect the superiority of fecal immunochemical tests over guaiac tests for colorectal cancer screening

The aim of this study was to compare the seasonal variation in performance of a faecal immunochemical test for haemoglobin (FIT) and a guaiac test (gFOBT) for colorectal cancer screening. From June 2009 to May 2011, 18,290 screening participants (50–74 years old) performed OC‐SENSOR quantitative FIT (1 sample) and Hemoccult II gFOBT (3 stool samples with 2 spots/sample). Referral for colonoscopy required a minimum of one positive spot (gFOBT), or a positive FIT [cut‐off 150 ng haemoglobin/mL buffer (i.e. 30 μg haemoglobin/g feces)]. The performance of tests for detection of advanced neoplasia was compared according to seasons using Receiver Operating Characteristics (ROC) curves, at various FIT cut‐off values. The positivity rate of FIT was significantly lower in the summer compared with other seasons (2.3% versus 3.0%, p = 0.03), whilst the positivity rate of gFOBT increased in the autumn (1.8% versus 1.5%, p = 0.11). FIT was clinically more effective than gFOBT over the four season‐specific ROC curves. At the cut‐off concentration used in the study, the season‐specific FIT/gFOBT ratios for true positive rates were: 2.8 (Autumn), 2.5 (Winter), 3.0 (Spring), 3.7 (Summer), and for false positive rates: 1.2 (Autumn), 1.5 (Winter), 1.8 (Spring), 0.9 (Summer). Therefore, in this study with this cut‐off concentration and in spite of lower positivity rate in summer, the seasonal variations of performance of OC‐SENSOR FIT led to improved gain in specificity in the summer, without a decrease in gain in sensitivity compared with gFOBT.     

Treatment‐related fatigue with sorafenib,sunitinib and pazopanib in patients with advanced solid tumors: An up‐to‐date review and meta‐analysis of clinical trials

Fatigue is the most common symptom associated with cancer and cancer treatment. We performed an up‐to‐date meta‐analysis to determine the incidence and relative risk (RR) of fatigue in patients (pts) with cancer treated with sorafenib (SO), sunitinib (SU) and pazopanib (PZ). PubMed databases were searched for articles published till August 2013. Eligible studies were selected according to PRISMA statement. Summary incidence, RR and 95% confidence intervals were calculated using random‐effects or fixed‐effects models based on the heterogeneity of selected studies. Fifteen studies were included in our analysis. A total of 6,996 pts was enrolled: 2,260 had renal cell carcinomas (RCC), 1,691 non‐small cell lung cancers, 1,290 breast cancers, 823 hepatocellular carcinomas, 362 soft tissue sarcomas, 304 gastrointestinal solid tumors, 165 neuroendocrine tumors and 101 melanomas. When stratified by drug, SO registered lower incidence and RR of all and high‐grade fatigue when compared to SU, whereas the difference between SO and PZ was significant only for all‐grade fatigue (p < 0.001). The difference between SU and PZ was significant for high‐grade (p < 0.001) but not for all‐grade fatigue (p = 0.52). In RCC pts, PZ showed the lower incidence and RR of all and high‐grade fatigue. The differences were significant for SU vs. SO (p < 0.001), SU vs. PZ (p < 0.001) and SO vs. PZ (p < 0.001). Treatment with SO, SU and PZ is associated with an increased incidence of fatigue in pts with cancer. Early and appropriate management is required to avoid unnecessary dose reductions and transitory or definitive treatment discontinuations.     

Dietary nitrate and nitrite and the risk of thyroid cancer in the NIH‐AARP Diet and Health Study

During the past several decades, an increasing incidence of thyroid cancer has been observed worldwide. Nitrate inhibits iodide uptake by the thyroid, potentially disrupting thyroid function. An increased risk of thyroid cancer associated with nitrate intake was recently reported in a cohort study of older women in Iowa. We evaluated dietary nitrate and nitrite intake and thyroid cancer risk overall and for subtypes in the National Institutes of Health‐American Association of Retired Persons (NIH‐AARP) Diet and Health Study, a large prospective cohort of 490,194 men and women, ages 50–71 years in 1995–1996. Dietary intakes were assessed using a 124‐item food frequency questionnaire. During an average of 7 years of follow‐up we identified 370 incident thyroid cancer cases (170 men, 200 women) with complete dietary information. Among men, increasing nitrate intake was positively associated with thyroid cancer risk (relative risk [RR] for the highest quintile versus lowest quintile RR = 2.28, 95% confidence interval [CI]: 1.29–4.041; p‐trend <0.001); however, we observed no trend with intake among women (p‐trend = 0.61). Nitrite intake was not associated with risk of thyroid cancer for either men or women. We evaluated risk for the two main types of thyroid cancer. We found positive associations for nitrate intake and both papillary (RR = 2.10; 95% CI: 1.09–4.05; p‐trend = 0.05) and follicular thyroid cancer (RR = 3.42; 95% CI: 1.03–11.4; p‐trend = 0.01) among men. Nitrite intake was associated with increased risk of follicular thyroid cancer (RR = 2.74; 95%CI: 0.86–8.77; p‐trend = 0.04) among men. Our results support a role of nitrate in thyroid cancer risk and suggest that further studies to investigate these exposures are warranted.     

A higher detection rate for colorectal cancer and advanced adenomatous polyp for screening with immunochemical fecal occult blood test than guaiac fecal occult blood test,despite lower compliance rate. A prospective,controlled, feasibility study

Immunochemical fecal occult blood test (FIT) is a new colorectal cancer (CRC) screening method already recommended by the American screening guidelines. We aimed to test the feasibility of FIT as compared to guaiac fecal occult blood test (G‐FOBT) in a large urban population of Tel Aviv. Average‐risk persons, aged 50–75 years, were offered FIT or G‐FOBT after randomization according to the socioeconomic status of their clinics. Participants with positive tests underwent colonoscopy. Participants were followed through the Cancer Registry 2 years after the study. Hemoccult SENSA? and OC‐MICRO? (three samples, 70 ng/ml threshold) were used. FIT was offered to 4,657 persons (Group A) and G‐FOBT to 7,880 persons (Group B). Participation rate was 25.9% and 28.8% in Group A and B, respectively (p < 0.001). Positivity rate in Group A and B was 12.7% and 3.9%, respectively (p < 0.001). Cancer found in six (0.49%) and eight (0.35%) patients of Group A and B, respectively (NS). Cancer registry follow‐up found missed cancer in five (0.22%) cases of Group B and none in Group A (NS). The sensitivity, specificity, negative and positive predictive value for cancer in Group A and B were 100%, 85.9%, 100%, 3.9% and 61.5%, 96.4%, 99.8%, 9.1%, respectively. There was increased detection of advanced adenomatous polyp (AAP) by FIT, irrespective of age, gender, and socioeconomic status (Per Protocol: odds ratio 2.69, 95% confidence interval 1.6–4.5; Intention to Screen: odds ratio 3.16, 95% confidence interval 1.8–5.4). FIT is feasible in urban, average‐risk population, which significantly improved performance for detection of AAP and CRC, despite reduced participation.     

Effects of α‐tocopherol and β‐carotene supplementation on cancer incidence and mortality: 18‐Year postintervention follow‐up of the Alpha‐Tocopherol,Beta‐Carotene Cancer Prevention Study

In the Alpha‐Tocopherol, Beta‐Carotene Cancer Prevention Study among 29,133 Finnish male smokers aged 50–69 years, daily α‐tocopherol (50 mg) for a median of 6.1 years decreased the risk of prostate cancer, whereas β‐carotene (20 mg) increased risk of lung cancer and overall mortality. To determine the postintervention effects of α‐tocopherol and β‐carotene, 25,563 men were followed 18 years for cancer incidence and all causes of mortality through national registers. Neither supplement had significant effects on post‐trial cancer incidence. Relative risk (RR) for lung cancer (n = 2,881) was 1.04 (95% confidence interval [CI], 0.96–1.11) among β‐carotene recipients compared with nonrecipients. For prostate cancer (n = 2,321), RR was 0.97 (95% CI, 0.89–1.05) among α‐tocopherol recipients compared with nonrecipients with the preventive effect of α‐tocopherol continuing ～8 years postintervention. Body mass index significantly modified the effect of α‐tocopherol on prostate cancer (p for interaction = 0.01) RR 1.00 (95% CI, 0.88–1.14) in normal‐weight men, 0.87 (95% CI, 0.77–0.98) in overweight men, and 1.25 (95% CI, 1.01–1.55) in obese men. The post‐trial relative mortality (based on 16,686 deaths) was 1.02 (95% CI, 0.98–1.05) for α‐tocopherol recipients compared with nonrecipients and 1.02 (95% CI, 0.99–1.05) for β‐carotene recipients compared with nonrecipients. α‐Tocopherol decreased post‐trial prostate cancer mortality (RR, 0.84; 95% CI, 0.70–0.99), whereas β‐carotene increased it (RR, 1.20; 95% CI, 1.01–1.42). In conclusion, supplementation with α‐tocopherol and β‐carotene appeared to have no late effects on cancer incidence. The preventive effect of moderate‐dose α‐tocopherol on prostate cancer continued several years post‐trial and resulted in lower prostate cancer mortality.     

Flavonoid intake and ovarian cancer risk in a population‐based case‐control study

Several recent studies have evaluated the association between dietary flavonoid intake and ovarian cancer risk, and all reported significant or suggestive inverse associations with certain flavonoids or flavonoid subclasses; however, most of these studies were small to moderate in size. We, therefore, examined this association in a large, population‐based case‐control study. We calculated intake of 5 common dietary flavonoids (myricetin, kaempferol, quercetin, luteolin, and apigenin), as well as total intake of these flavonoids, for 1,141 cases and 1,183 frequency‐matched controls. We used unconditional logistic regression to estimate the relative risk (RR) of ovarian cancer for each quintile of flavonoid intake when compared with the lowest quintile. We did not observe an association between total flavonoid intake and ovarian cancer risk. The multivariable‐adjusted RR for the highest versus lowest quintile of total flavonoid intake was 1.06 (95% confidence interval [CI] = 0.78–1.45). In analyses of each individual flavonoid, only intake of apigenin was associated with a borderline significant decrease in risk (RR, highest vs. lowest quintile = 0.79, 95% CI = 0.59–1.06; p‐trend = 0.26), and this association was significant after adjustment for intake of the other 4 individual flavonoids (comparable RR = 0.72, 95% CI = 0.53–0.98; p‐trend = 0.09). These results provide limited support for an association between flavonoid intake and ovarian cancer risk. However, given the findings of previous studies and the biologic plausibility of this association, additional studies are warranted. © 2008 Wiley‐Liss, Inc.     

Cutaneous melanoma attributable to solar radiation in Cali,Colombia

Estimating the population attributable fraction (PAF) of melanomas due to sun exposure is challenging as there are no unexposed population nor reliable exposure data. In high incidence countries, a historic cohort of the South Thames cancer registry was used as a minimally exposed population using the formula PAF = (observed incidence‐incidence in minimally exposure)/observed incidence. In this study, we apply this method, constructing a minimally exposed cohort for Colombia and also using the historical South Thames data, using melanoma incidence data from the population‐based cancer registry of Cali, Colombia for the period 1967–2012. The historic cohort incidence rates were very similar to those of Thames, but cohort effects were smaller for women and nonexistent for men. Age‐specific incidence rates of these minimally exposed cohorts were applied to recent population numbers. For females, PAFs were 19% using the historic Thames cohort and 25% using the historic Cali cohort, corresponding numbers for males were 62% (vs. Thames) and 0% (vs. Cali). Taking into account the incidence rates of acral melanomas, which are not sun related, the PAF increased in women to 26% (vs. Thames) and 34% (vs. Cali) and for men 77% (vs. Thames). This exercise shows the modest contribution of exposure to ultraviolet radiation in the burden of melanoma in low‐incidence countries, as well as the importance to take into consideration the acral lentiginous melanomas.     

Changes in the choice of colorectal cancer screening tests in primary care settings from 7,845 prospectively collected surveys

Purpose

Colorectal cancer (CRC) is one of the leading causes of cancer mortality worldwide. This study examined factors influencing the choice of participants between colonoscopy and fecal immunochemical test (FIT) in a screening program and the impact of an unbiased educational session on influencing this decision.

Methods

Data from 7,845 participants who underwent screening between May 2008 and April 2011 was analyzed. Binary logistic regression and multinomial regression were performed to calculate the odds of selection of colonoscopy instead of FIT and the impact of the educational session on final participant choice, respectively.

Results

Of the 7,845 participants, 4,796 (61?%) underwent FIT and 3,049 (39?%) underwent colonoscopy. A significant number of participants changed their initial choice after the educational session, with 27.1?% changing to FIT from colonoscopy and 8?% changing from FIT to colonoscopy. Age, educational level, occupation, income, family history of CRC, perception of risk of CRC, and perceptions regarding CRC screening were significantly different among the groups choosing FIT and colonoscopy. Family history of CRC and high self-perception of CRC risk resulted in higher odds of choosing colonoscopy, whereas older age, single marital status, and negative perception of CRC screening resulted in lower odds. Perceptions of overall health status, occupation, low income, younger age, and negative perceptions of CRC screening were associated with higher odds of change in screening choice.

Conclusions

Those at higher odds of changing CRC screening options should be supported with more detailed explanations by primary care physicians to secure a more informed and considered choice.     

Red and processed meat,nitrite, and heme iron intakes and postmenopausal breast cancer risk in the NIH‐AARP Diet and Health Study

Previous studies have shown inconsistent associations between red and processed meat intake and breast cancer risk. N‐nitroso compounds and heme iron have been hypothesized as contributing factors. We followed 193,742 postmenopausal women in the NIH‐AARP Diet and Health Study and identified 9,305 incident breast cancers (1995–2006). Dietary intake was assessed using a food frequency questionnaire at baseline. We adjusted daily intakes of meat, nitrite and heme iron for energy intake using the nutrient density method. We estimated multivariable‐adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) by quintiles of dietary exposures for all breast cancer, by stage (in‐situ, localized, regional/distant) and by estrogen/progesterone receptor (ER/PR) status using Cox proportional hazards regression. Total red meat intake was positively associated with risk of regional/distant cancer (p‐trend = 0.02). The risk was 25% higher in the highest vs. lowest intake quintile (95% CI = 1.03–1.52). Higher processed red meat intake (Q5 vs. Q1) was associated with 27% higher risk of localized breast cancer (95% CI = 1.01–1.27, p‐trend = 0.03) and a 19% higher risk of regional/distant cancer (95% CI = 0.98–1.44, p‐trend = 0.10). In addition, higher nitrite intake from processed red meat was positively associated with localized cancer (HR for Q5 vs. Q1 = 1.23, 95% CI = 1.09–1.39, p‐trend < 0.0001). Heme iron intake was positively associated with breast cancer risk overall and all cancer stages (p‐trend = 0.02–0.05). No heterogeneity was observed in risk associations by hormone receptor status. Our findings suggest that high consumption of red meat and processed meat may increase risk of postmenopausal breast cancer. Added nitrite and heme iron may partly contribute to these observed associations.     

Associations of insulin‐like growth factor and insulin‐like growth factor binding protein‐3 with mortality in women with breast cancer

Elevated circulating insulin‐like growth factor‐1 (IGF‐1), a breast epithelial cell mitogen, is associated with breast cancer development. However, its association with breast cancer survival is not established. Circulating concentrations of IGF‐1 are controlled via binding proteins, including IGF Binding Protein‐3 (IGFBP‐3), that may modulate the association of IGF‐1 with breast‐cancer outcomes. We measured IGF‐1 and IGFBP‐3 concentrations in serum from 600 women enrolled in the health, eating, activity, and lifestyle (HEAL) study, a multiethnic, prospective cohort study of women diagnosed with stage I‐IIIA breast cancer. We evaluated the association between IGF‐1 and IGFBP‐3, and as a ratio, modeled using quintile cut‐points, with risk of breast cancer‐specific (n = 42 deaths) and all‐cause mortality (n = 87 deaths) using Cox proportional hazards models. In models adjusted for body mass index, ethnicity, tamoxifen use at time of blood draw, treatment received at diagnosis and IGFBP‐3, women in the highest quintile of IGF‐1 level had an increased risk of all‐cause mortality (Hazard Ratio (HR) = 3.10, 95% CI 1.21–7.93, p = 0.02), although no dose‐response association was evident. The IGF‐1/IGFBP‐3 ratio, an indicator of free IGF‐I levels, was significantly associated with increasing risk of all‐cause mortality (HR = 2.83, 95% CI 1.25–6.36 p_trend = 0.01, upper vs. lower quintile) in a fully adjusted model. In conclusion, high serum levels of IGF‐1 and the IGF‐1/IGFBP‐3 ratio were associated with increased risk of all‐cause mortality in women with breast cancer. These results need to be confirmed in larger breast cancer survivor cohorts.     

Plasma phospholipid fatty acids,dietary fatty acids and prostate cancer risk

Animal and experimental studies have demonstrated that long‐chain n‐3 fatty acids inhibit the development of prostate cancer, whereas n‐6 fatty acids might promote it. We performed a case–cohort analysis within the Melbourne Collaborative Cohort Study using a random sample of 1,717 men and 464 prostate cancer cases to investigate associations between fatty acids assessed in plasma phospholipids (PPLs) or diet (estimated using a 121‐item food frequency questionnaire) and prostate cancer risk. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression. Prostate cancer risk was positively associated with %PPL saturated fatty acids (SFAs); HR [95% CI] = 1.51 [1.06, 2.16] (Q5 vs. Q1, fifth vs. first quintile); p‐trend = 0.003. HRs (Q5 to Q2 vs. Q1) were significantly elevated for %PPL palmitic acid. %PPL oleic acid was inversely associated with risk, HR = 0.62 [0.43, 0.91] (Q5 vs. Q1); p‐trend = 0.04. No statistically significant linear trends were observed for dietary intakes. The HRs were elevated for moderate intakes of linoleic acid (Q2 and Q3 vs. Q1, 1.58 [1.10, 2.28] and 1.70 [1.18, 2.46], respectively), but the increase was not significant for higher intakes (Q4 and Q5). No association varied significantly by tumour aggressiveness (all p‐homogeneity > 0.1). Prostate cancer risk was positively associated with %PPL SFA, largely attributable to palmitic acid and inversely associated with %PPL monounsaturated fatty acids, largely attributable to oleic acid. Higher risks were also observed for dietary n‐6 polyunsaturated fats, primarily linoleic acid.