Coffee intake and the risk of colorectal adenoma: The colorectal adenoma study in Tokyo

Coffee is a commonly consumed beverage which contains several potential anticarcinogenic and chemopreventive compounds, and has been hypothesized to have protective effects in colorectal neoplasia. However, the limited available data on coffee consumption in relation to colorectal adenoma (CRA), a precursor lesion to most colorectal cancers, remain largely inconsistent. In this study, we evaluated the association of coffee intake with the risk of CRA in a middle‐aged Japanese population. Study subjects were selected from examinees who underwent total colonoscopy as part of a cancer screening program and responded to self‐administered dietary and lifestyle questionnaires. A total of 738 patients with adenoma and 697 controls were included in the study. Coffee intake was assessed with a food frequency questionnaire, and divided into quartiles based on the distribution among controls. Unconditional logistic regression models were used to estimate odds ratio (OR) and 95% confidence interval (CI) of CRA, with adjustment for potential confounding factors. High coffee consumption was associated with a reduced risk of CRA, with a multivariate‐adjusted OR for the highest versus lowest quartile of coffee intake of 0.67 (95% CI = 0.48–0.93; p_trend = 0.02). The inverse association of coffee intake was limited to proximal (OR = 0.64; 95%CI = 0.44–0.95; p_trend = 0.04) and distal colon adenoma (OR = 0.62; 95%CI = 0.39–0.99; p_trend = 0.06), and appeared to be more evident with small (OR = 0.68; 95%CI = 0.49–0.96; p_trend = 0.04) and single adenomas (OR = 0.65; 95%CI = 0.44–0.95; p_trend = 0.02). Green tea intake was not found to be associated with CRA risk. This study provides support for the protective effect of coffee drinking on colon adenomas, a precursor of colon cancer.     

Circulating prolactin and breast cancer risk among pre- and postmenopausal women in the EPIC cohort

BackgroundExperimental and epidemiological evidence suggests that prolactin might play a role in the etiology of breast cancer. We analyzed the relationship of prediagnostic circulating prolactin levels with the risk of breast cancer by menopausal status, use of postmenopausal hormone replacement therapy (HRT) at blood donation, and by estrogen and progesterone receptor status of the breast tumors.Patients and methodsConditional logistic regression was used to analyze the data from a case–control study nested within the prospective European EPIC cohort, including 2250 invasive breast cancer and their matched control subjects.ResultsStatistically significant heterogeneity in the association of prolactin levels with breast cancer risk between women who were either pre- or postmenopausal at the time of blood donation was observed (P_het = 0.04). Higher serum levels of prolactin were associated with significant increase in the risk of breast cancer among postmenopausal women [odds ratio (OR)_Q4–Q1 = 1.29 (95% confidence interval, CI, 1.05–1.58), P_trend = 0.09]; however, this increase in risk seemed to be confined to women who used postmenopausal HRT at blood donation [OR_Q4–Q1 = 1.45 (95% CI 1.08–1.95), P_trend = 0.01], whereas no statistically significant association was found for the non-users of HRT [OR_Q4–Q1 = 1.11 (95%CI 0.83–1.49), P_trend = 0.80] (P_het = 0.08). Among premenopausal women, a statistically non-significant inverse association was observed [OR_Q4–Q1 = 0.70 (95% CI 0.48–1.03), P_trend = 0.16]. There was no heterogeneity in the prolactin–breast cancer association by hormone receptor status of the tumor.ConclusionOur study indicates that higher circulating levels of prolactin among the postmenopausal HRT users at baseline may be associated with increased breast cancer risk.     

Alcohol drinking and colorectal cancer risk: an overall and dose–response meta-analysis of published studies

BackgroundThe International Agency for Research on Cancer (IARC) concluded that alcohol consumption is related to colorectal cancer (CRC). However, several issues remain unresolved, including quantification of the association for light (≤1 drink/day) and moderate (2–3 drinks/day) alcohol drinking, investigation of the dose–response relationship, and potential heterogeneity of effects by sex, colorectal site, and geographical region.MethodsTwenty-seven cohort and 34 case–control studies presenting results for at least three categories of alcohol intake were identified from a PubMed search of articles published before May 2010. The summary relative risks (RRs) were estimated by the random effects model. Second-order fractional polynomials and random effects meta-regression models were used for modeling the dose–risk relation.ResultsThe RRs were 1.21 [95% confidence interval (CI) 1.13–1.28] for moderate and 1.52 (95% CI 1.27–1.81) for heavy (≥4 drinks/day) alcohol drinking. The RR for moderate drinkers, compared with non-/occasional drinkers, was stronger for men (RR = 1.24, 95% CI 1.13–1.37) than for women (RR = 1.08, 95% CI 1.03–1.13; P_{heterogeneity} = 0.02). For heavy drinkers, the association was stronger in Asian studies (RR = 1.81, 95% CI 1.33–2.46; P_{heterogeneity} = 0.04). The dose–risk analysis estimated RRs of 1.07 (95% CI 1.04–1.10), 1.38 (95% CI 1.28–1.50), and 1.82 (95% CI 1.41–2.35) for 10, 50, and 100 g/day of alcohol, respectively.ConclusionsThis meta-analysis provides strong evidence for an association between alcohol drinking of >1 drink/day and colorectal cancer risk.     

Inverse associations of dietary fiber and menopausal hormone therapy with colorectal cancer risk in the Multiethnic Cohort Study

In the Multiethnic Cohort Study, we previously reported that dietary fiber intake was inversely associated with colorectal cancer risk in men only. In women, the inverse relationship was weaker and appeared to be confounded by menopausal hormone therapy (MHT). We re‐examined this observation with a greatly increased power. Using Cox proportional hazards models, we analyzed data from 187,674 participants with 4,692 cases identified during a mean follow‐up period of 16 years. In multivariable‐adjusted models, dietary fiber intake was inversely associated with colorectal cancer risk in both sexes: HR = 0.73, 95% CI: 0.61–0.89 for highest vs. lowest quintile, p_trend = 0.0020 in men and HR = 0.76, 95% CI: 0.62–0.91, p_trend = 0.0067 in women. Postmenopausal women who ever used MHT had a 19% lower risk of colorectal cancer (95% CI: 0.74–0.89) compared with MHT never users. In a joint analysis of dietary fiber and MHT, dietary fiber intake was associated with a lower colorectal cancer risk in MHT never users (HR = 0.75, 95% CI: 0.59–0.95, p_trend = 0.045), but did not appear to further decrease the colorectal cancer risk of MHT ever users (p_trend = 0.11). Our results support the overall protective roles of dietary fiber and MHT against colorectal cancer and suggest that dietary fiber may not lower risk further among women who ever used MHT. If confirmed, these results would suggest that MHT and dietary fiber may share overlapping mechanisms in protecting against colorectal cancer.     

Healthy dietary patterns and incidence of biliary tract and gallbladder cancer in a prospective study of women and men

BackgroundWhether diet influences the risk of biliary tract cancer (BTC) is unknown. We examined the associations of two healthy dietary patterns, including a modified Dietary Approach to Stop Hypertension (mDASH) diet and a modified Mediterranean (mMED) diet, with the incidence of BTC in a population-based prospective study.MethodsThe study population comprised 76,014 Swedish adults who were 45–83 years of age and cancer-free at baseline. The mDASH and mMED diets were calculated from self-reported dietary data collected by a validated food-frequency questionnaire. Cox proportional hazards regression models were used to estimate hazard ratios (HR) with 95% confidence intervals (CI) adjusted for potential confounders.ResultsOver 1,010,777 person-years (mean 13.3 years) of follow-up, 140 extrahepatic BTC cases (including 77 gallbladder cancers) and 23 intrahepatic BTC cases were ascertained by linkage with the Swedish Cancer Register. Adherence to the mDASH and mMED diets was statistically significantly inversely associated with risk of extrahepatic BTC (P_trend ≤ 0.0003) and gallbladder cancer (P_trend ≤ 0.005) but not intrahepatic BTC (P_trend ≥ 0.11). The multivariable HRs (95% CI) for the highest versus lowest tertile of the mDASH diet were 0.41 (0.26–0.64) for extrahepatic BTC and 0.36 (0.20–0.64) for gallbladder cancer. The corresponding HRs (95% CI) for the mMED diet were respectively 0.41 (0.25–0.67) and 0.42 (0.23–0.79).ConclusionAdherence to a healthy diet may play a role in reducing the risk of extrahepatic BTC.     

Body mass index and incidence of localized and advanced prostate cancer--a dose-response meta-analysis of prospective studies

BackgroundThe relationship between obesity and risk of prostate cancer (PCa) is unclear; however, etiologic heterogeneity by subtype of PCa (localized, advanced) related to obesity was suggested. Therefore, we conducted a dose–response meta-analysis of prospective studies to assess the association between body mass index (BMI) and risk of localized and advanced PCa.Materials and methodsRelevant prospective studies were identified by a search of Medline and Embase databases to 03 October 2011. Twelve studies on localized PCa (1 033 009 men, 19 130 cases) and 13 on advanced PCa (1 080 790 men, 7067 cases) were identified. We carried out a dose–response meta-analysis using random-effects model.ResultsFor localized PCa, we observed an inverse linear relationship with BMI [P_trend < 0.001, relative risk (RR): 0.94 (95% confidence interval, 95% CI, 0.91–0.97) for every 5 kg/m² increase]; there was no evidence of heterogeneity (P_{heterogeneity} = 0.27). For advanced PCa, we observed a linear direct relationship with BMI (P_trend = 0.001, RR: 1.09 (95% CI 1.02–1.16) for every 5 kg/m² increase); there was weak evidence of heterogeneity (P_{heterogeneity} = 0.08). Omitting one study that contributed substantially to the heterogeneity yielded a pooled RR of 1.07 (95% CI 1.01–1.13) for every 5 kg/m² increase (P_{heterogeneity} = 0.26).ConclusionsThe quantitative summary of the accumulated evidence indicates that obesity may have a dual effect on PCa—a decreased risk for localized PCa and an increased risk for advanced PCa.     

Plasma methionine,choline, betaine,and dimethylglycine in relation to colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC)

BackgroundDisturbances in one carbon metabolism may contribute to carcinogenesis by affecting methylation and synthesis of DNA. Choline and its oxidation product betaine are involved in this metabolism and can serve as alternative methyl group donors when folate status is low.Patients and methodsWe conducted a case–control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), to investigate plasma concentrations of the methyl donors methionine, choline, betaine (trimethylglycine), and dimethylglycine (DMG) in relation to colorectal cancer (CRC) risk. Our study included 1367 incident CRC cases (965 colon and 402 rectum) and 2323 controls matched by gender, age group, and study center. Multivariate-adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for CRC risk were estimated by conditional logistic regression, comparing the fifth to the first quintile of plasma concentrations.ResultsOverall, methionine (OR: 0.79, 95% CI: 0.63–0.99, P-trend = 0.05), choline (OR: 0.77, 95% CI: 0.60–0.99, P-trend = 0.07), and betaine (OR: 0.85, 95% CI: 0.66–1.09, P-trend = 0.06) concentrations were inversely associated with CRC risk of borderline significance. In participants with folate concentration below the median of 11.3 nmol/l, high betaine concentration was associated with reduced CRC risk (OR: 0.71, 95% CI: 0.50–1.00, P-trend = 0.02), which was not observed for those having a higher folate status. Among women, but not men, high choline concentration was associated with decreased CRC risk (OR: 0.62, 95% CI: 0.43–0.88, P-trend = 0.01). Plasma DMG was not associated with CRC risk.ConclusionsIndividuals with high plasma concentrations of methionine, choline, and betaine may be at reduced risk of CRC.     

Next-generation sequencing identifies germline MRE11A variants as markers of radiotherapy outcomes in muscle-invasive bladder cancer

BackgroundMuscle-invasive bladder cancer (MIBC) can be cured by radical radiotherapy (RT). We previously found tumour MRE11 expression to be predictive of survival following RT in MIBC, and this was independently validated in a separate institute. Here, we investigated germline MRE11A variants as possible predictors of RT outcomes in MIBC, using next-generation sequencing (NGS).Patients and methodsThe MRE11A gene was amplified in germline DNA from 186 prospectively recruited MIBC patients treated with RT and sequenced using bar-coded multiplexed NGS. Germline variants were analysed for associations with cancer-specific survival (CSS). For validation as a prognostic or predictive marker, rs1805363 was then genotyped in a cystectomy-treated MIBC cohort of 256 individuals. MRE11A mRNA isoform expression was measured in bladder cancer cell lines and primary tumour samples.ResultsCarriage of at least one of six (five novel) rare variants was associated with the worse RT outcome (hazard ratio [HR] 4.04, 95% confidence interval [95% CI] 1.42–11.51, P = 0.009). The single-nucleotide polymorphism (SNP), rs1805363 (minor allele frequency 11%), was also associated with worse CSS (per-allele HR 2.10, 95% CI 1.34–3.28, P_trend = 0.001) following RT in MIBC, with a gene-dosage effect observed, but no effect seen on CSS in the cystectomy cohort (P_trend = 0.89). Furthermore, rs1805363 influenced relative MRE11A isoform expression, with increased isoform 2 expression with carriage of the rs1805363 minor A allele.ConclusionsGermline MRE11A SNP rs1805363 was predictive of RT, but not of cystectomy outcome in MIBC. If successfully validated in an independent RT-treated cohort, this SNP could be a useful clinical tool for selecting patients for bladder-conserving treatment.     

Dietary consumption and diet diversity and risk of developing bladder cancer: results from the South and East China case–control study

Background

The epidemiologic evidence on the role of dietary consumption on the risk of bladder cancer in the Chinese population is limited. We investigated the role of dietary consumption and diet diversity on the risk of developing bladder cancer within a Chinese population.

Methods

A case–control study of 487 cases and 469 controls was conducted in four hospitals in China. A food frequency questionnaire was used to gather information on the consumption of 35 food items. Unconditional logistic regression models were used to derive odds ratios (ORs) and corresponding 95 % confidence intervals (95 % CI) for the relationship between dietary factors, dietary diversity scores, and bladder cancer.

Results

The ORs of bladder cancer for red meat (OR = 1.8, 95 % CI:1.1–3.0;p _trend = 0.01), organ meat (OR = 1.6, 95 % CI:0.9–2.9;p _trend = 0.04), leafy vegetables (OR = 2.9, 95 % CI:1.6–5.4;p _trend = 0.003), bulb vegetables (OR = 2.3, 95 % CI:1.3–4.0;p _trend = 0.003), and preserved vegetables (OR = 2.3, 95 % CI:1.2–4.2;p _trend = 0.02) were significantly increased when comparing the highest to lowest level of consumption. The ORs for white fresh fish (OR = 0.5, 95 % CI:0.3–0.9;p _trend = 0.004), citrus fruits (OR = 0.4, 95 % CI:0.3–0.8;p _trend = 0.007), stone fruits (OR = 0.4, 95 % CI:0.2–0.6;p _trend < 0.001), vine fruits (OR = 0.5, 95 % CI:0.2–1.0;p _trend = 0.02), flower vegetables (OR = 0.3, 95 % CI:0.2–0.6;p _trend < 0.001), potatoes (OR = 0.4, 95 % CI:0.2–0.9;p _trend = 0.005), or dairy products (OR = 0.4, 95 % CI:0.3–0.7;p _trend < 0.001) were significantly decreased when comparing the highest to lowest level of consumption. Subjects with the highest total diet diversity (OR = 0.4, 95 % CI:0.2–1.1;p _trend = 0.02) and fruit diversity (OR = 0.1, 95 % CI:0.0–0.3;p _trend < 0.001) had reduced ORs of and compared to subjects with the lowest diversity.

Conclusion

Our results indicate that a diet with higher total diet diversity and in particular fruit diversity may reduce the risk of bladder cancer.     

Analysis of HER-3, insulin growth factor-1, nuclear factor-kB and epidermal growth factor receptor gene copy number in the prediction of clinical outcome for K-RAS wild-type colorectal cancer patients receiving irinotecan-cetuximab

BackgroundA large proportion of colorectal cancer patients does not benefit from the use of anti-epidermal growth factor receptor (EGFR) treatment although in the absence of a mutation of the K-RAS gene. Preliminary observations suggested that HER-3, insulin-like growth factor-1 (IGF-1), nuclear factor-kB (NF-kB) and EGFR gene copy number (GCN) might identify patients not likely to benefit from anti-EGFR therapy. We tested the interaction between HER-3, IGF-1, NF-kB, EGFR GCN and K-RAS mutational analysis to verify the relative ability of these variables to identify a subgroup of patients more likely to benefit from EGFR-targeted treatment among those harbouring a K-RAS wild-type status.Patients and methodsWe retrospectively collected tumours from 168 patients with metastatic colorectal cancer treated with irinotecan–cetuximab. K-RAS was assessed with direct sequencing, EGFR amplification was assessed by chromogenic in situ hybridisation (CISH) and HER-3, IGF-1 and NF-kB were assessed by immunohistochemistry.ResultsIn patients with K-RAS wild-type tumours, the following molecular factors resulted independently associated with response rate: HER-3 [odds ratio (OR) = 4.6, 95% confidence interval (CI) 1.8–13.6, P = 0.02], IGF-1 (OR = 4.2, 95% CI 2–10.2, P = 0.003) and EGFR GCN (OR = 4.1, 95% CI 1.9–26.2, P = 0.04). These factors also independently correlated with overall survival as follows: HER-3 [hazard ratio (HR) = 0.4, 95% CI 0.28–0.85, P = 0.008], IGF-1 (HR = 0.47, 95% CI 0.24–0.76, P < 0.0001) and EGFR GCN (HR = 0.59, 95% CI 0.22–0.89, P = 0.04).DiscussionWe believe that our data may help further composing the molecular mosaic of EGFR-resistant tumours. The role of HER-3, IGF-1 and CISH EGFR GCN should be prospectively validated in clinical trials investigating anti-EGFR treatment strategies in colorectal cancer patients.     

Associations of Early Medicaid Expansion With Insurance Status and Stage at Diagnosis Among Cancer Patients Receiving Radiation Therapy

PurposeMedicaid expansion in 2014 is associated with improved insurance coverage and stage at diagnosis in cancer patients. However, little is known about the effect of early Medicaid expansions in 2010 to 2011 on outcomes in radiation therapy recipients. The objective of this study was to estimate the effect of early Medicaid expansion on insurance status and stage at diagnosis among radiation therapy recipients.Methods and MaterialsThe Surveillance, Epidemiology, and End Results database was queried for cases aged 18 to 64 diagnosed in 2007 to 2013 with a first primary malignancy treated with radiation therapy. Difference-in-differences analyses were used to compare changes in insurance coverage and stage at diagnosis from 2007 to 2009 and 2011 to 2013 in expansion relative to nonexpansion states.ResultsThere was a –0.48 (95% confidence interval [CI], –0.84 to –0.13; P = .007) percentage point (PP) reduction in uninsured in expansion relative to nonexpansion states, primarily among counties with lower educational attainment (–1.73 PP; 95% CI, –2.72 to –0.75). Increases in early stage diagnoses in expansion relative to nonexpansion states were found overall and in breast (1.56 PP; 95% CI, 0.45-2.68; P = .006), colorectal (3.72 PP; 95% CI, 0.33-7.12; P = .032), and lung (1.49 PP; 95% CI, 0.25-2.72; P = .018) cancers. Decreases in late stage diagnoses were found in cervical (–5.91 PP; 95% CI, –9.58 to –2.25; P = .002), colorectal (–2.72 PP; 95% CI, –5.43 to –0.01; P = .05), and lung (–3.28 PP; 95% CI, –5.47 to –1.1; P = .003) cancers.ConclusionsFor radiation therapy recipients, early Medicaid expansion was associated with decreased percent uninsured, particularly among low education counties, and earlier stage diagnoses for screenable cancers. Thus, early Medicaid expansion may improve access to care and decrease disparities for radiation therapy recipients.     

Associations of bread and pasta with the risk of cancer of the breast and colorectum

BackgroundCarbohydrate foods with high glycemic and insulinemic potential may influence cancer risk possibly through the insulin/growth-factor axis. Two staple carbohydrate foods of the Mediterranean diet, bread and pasta, have different glycemic and insulinemic responses and hence may affect cancer risk differently.Materials and methodsWe studied the association of bread and pasta with breast and colorectal cancer risk using data from two Italian case–control studies. These studies included 2569 women with histologically confirmed breast cancer and 1953 men and women with colorectal cancer. Controls were 2588 and 4154, respectively, admitted to the same hospitals as cases for acute, non-neoplastic conditions. Multivariate odds ratios (ORs) were obtained after allowance for relevant confounding factors.ResultsThe ORs of breast cancer for the highest versus the lowest quintile were 1.28 (95% confidence interval, CI: 1.03–1.58, P-trend = 0.0342) for bread and 1.07 (95% CI: 0.88–1.31, P-trend = 0.7072) for pasta. The association with bread remained virtually unchanged with postmenopause and overweight. The ORs of colorectal cancer in women for the highest versus the lowest quintile were 2.02 (95% CI: 1.46–2.80, P-trend = 0.0002) for bread and 1.37 (95% CI: 1.00–1.88, P-trend = 0.0164) for pasta. The associations remained significant only for bread in strata of menopausal status and in women with overweight. No significant associations were seen in men for either bread or pasta.ConclusionsOverall, these two cancer case–control studies showed stronger positive associations with bread than pasta in women, particularly if overweight, suggesting possible hormonal-related mechanisms.     

Genetic variation at CYP3A is associated with age at menarche and breast cancer risk: a case-control study

Introduction

We have previously shown that a tag single nucleotide polymorphism (rs10235235), which maps to the CYP3A locus (7q22.1), was associated with a reduction in premenopausal urinary estrone glucuronide levels and a modest reduction in risk of breast cancer in women age ≤50 years.

Methods

We further investigated the association of rs10235235 with breast cancer risk in a large case control study of 47,346 cases and 47,570 controls from 52 studies participating in the Breast Cancer Association Consortium. Genotyping of rs10235235 was conducted using a custom Illumina Infinium array. Stratified analyses were conducted to determine whether this association was modified by age at diagnosis, ethnicity, age at menarche or tumor characteristics.

Results

We confirmed the association of rs10235235 with breast cancer risk for women of European ancestry but found no evidence that this association differed with age at diagnosis. Heterozygote and homozygote odds ratios (ORs) were OR = 0.98 (95% CI 0.94, 1.01; P = 0.2) and OR = 0.80 (95% CI 0.69, 0.93; P = 0.004), respectively (P_trend = 0.02). There was no evidence of effect modification by tumor characteristics. rs10235235 was, however, associated with age at menarche in controls (P_trend = 0.005) but not cases (P_trend = 0.97). Consequently the association between rs10235235 and breast cancer risk differed according to age at menarche (P_het = 0.02); the rare allele of rs10235235 was associated with a reduction in breast cancer risk for women who had their menarche age ≥15 years (OR_het = 0.84, 95% CI 0.75, 0.94; OR_hom = 0.81, 95% CI 0.51, 1.30; P_trend = 0.002) but not for those who had their menarche age ≤11 years (OR_het = 1.06, 95% CI 0.95, 1.19, OR_hom = 1.07, 95% CI 0.67, 1.72; P_trend = 0.29).

Conclusions

To our knowledge rs10235235 is the first single nucleotide polymorphism to be associated with both breast cancer risk and age at menarche consistent with the well-documented association between later age at menarche and a reduction in breast cancer risk. These associations are likely mediated via an effect on circulating hormone levels.     

IVS10+12A>G polymorphism in hMSH2 gene associated with prognosis for patients with colorectal cancer

BackgroundThe polymorphisms in DNA repair genes may contribute to a variation in the DNA repair capacity, thereby affecting the risk of carcinogenesis and prognosis of colorectal cancer. Accordingly, the present study analyzed 14 polymorphisms in DNA repair genes and their impact on the prognosis for patients with colorectal cancer.Materials and methodsThree hundred and ninety-seven consecutive patients with curatively resected colorectal adenocarcinoma were enrolled in the present study. The genomic DNA was extracted from fresh colorectal tissue and 14 polymorphisms of DNA repair genes determined using a real-time PCR genotyping assay.ResultsThe median age of the patients was 63 years, and 218 (54.9%) patients had colon cancer, while 179 (45.1%) patients had rectal cancer. A multivariate survival analysis, including age, differentiation, carcinoembryonic antigen level, and stage, revealed a better survival for the patients with the combined IVS10+12AG and GG genotype than for the patients with the IVS10+12AA genotype [disease-free survival: hazard ratio (HR) 0.47, 95% confidence interval (CI) 0.30–0.75, P = 0.002; overall survival: HR 0.50, 95% CI 0.26–0.98, P = 0.042]. None of the other polymorphisms was associated with survival.ConclusionThe IVS10+12A>G polymorphism in the hMSH2 gene was found to be an independent prognostic marker for patients with colorectal cancer.     

Predicted vitamin D status and colon cancer recurrence and mortality in CALGB 89803 (Alliance)

BackgroundObservational studies suggest that higher levels of 25-hydroxyvitamin D₃ (25(OH)D) are associated with a reduced risk of colorectal cancer and improved survival of colorectal cancer patients. However, the influence of vitamin D status on cancer recurrence and survival of patients with stage III colon cancer is unknown.Patients and methodsWe prospectively examined the influence of post-diagnosis predicted plasma 25(OH)D on outcome among 1016 patients with stage III colon cancer who were enrolled in a National Cancer Institute-sponsored adjuvant therapy trial (CALGB 89803). Predicted 25(OH)D scores were computed using validated regression models. We examined the influence of predicted 25(OH)D scores on cancer recurrence and mortality (disease-free survival; DFS) using Cox proportional hazards.ResultsPatients in the highest quintile of predicted 25(OH)D score had an adjusted hazard ratio (HR) for colon cancer recurrence or mortality (DFS) of 0.62 (95% confidence interval [CI], 0.44–0.86), compared with those in the lowest quintile (P_trend = 0.005). Higher predicted 25(OH)D score was also associated with a significant improvement in recurrence-free survival and overall survival (P_trend = 0.01 and 0.0004, respectively). The benefit associated with higher predicted 25(OH)D score appeared consistent across predictors of cancer outcome and strata of molecular tumor characteristics, including microsatellite instability and KRAS, BRAF, PIK3CA, and TP53 mutation status.ConclusionHigher predicted 25(OH)D levels after a diagnosis of stage III colon cancer may be associated with decreased recurrence and improved survival. Clinical trials assessing the benefit of vitamin D supplementation in the adjuvant setting are warranted.ClinicalTrials.gov IdentifierNCT00003835     

Adult weight gain and colorectal adenomas—a systematic review and meta-analysis

BackgroundColorectal adenomas are known as precursors for the majority of colorectal carcinomas. While weight gain during adulthood has been identified as a risk factor for colorectal cancer, the association is less clear for colorectal adenomas. We conducted a systematic review and meta-analysis to quantify the evidence on this association.MethodsWe searched Medline up to September 2016 to identify observational (prospective, cross-sectional and retrospective) studies on weight gain during adulthood and colorectal adenoma occurrence and recurrence. We conducted meta-analysis on high weight gain versus stable weight, linear and non-linear dose–response meta-analyses to analyze the association. Summary odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using a random effects model.ResultsFor colorectal adenoma occurrence, the summary OR was 1.39 (95% CI: 1.17–1.65;I²: 43%,N = 9 studies, cases = 5507) comparing high (midpoint: 17.4 kg) versus stable weight gain during adulthood and with each 5 kg weight gain the odds increased by 7% (2%–11%;I²: 65%,N = 7 studies). Although there was indication of non-linearity (P_{non-linearity} < 0.001) there was an increased odds of colorectal adenoma throughout the whole range of weight gain. Three studies were identified investigating the association between weight gain and colorectal adenoma recurrence and data were limited to draw firm conclusions.ConclusionsEven a small amount of adult weight gain was related to a higher odds of colorectal adenoma occurrence. Our findings add to the benefits of weight control in adulthood regarding colorectal adenoma occurrence, which might be relevant for early prevention of colorectal cancer.     

Adolescent and mid‐life diet and subsequent risk of thyroid cancer in the NIH‐AARP diet and health study

Although thyroid cancer is suspected to have a nutritional etiology, prospective studies examining the relationship between diet and thyroid cancer are lacking. During 1996–1997, NIH‐AARP Diet and Health Study participants, ages 51–72 years, completed a 37‐item food frequency questionnaire about diet at ages 12–13 years (adolescence) and 10 years before baseline (mid‐life). Over a median 10 years of follow‐up, 325 individuals (143 men and 182 women) were diagnosed with thyroid cancer. Multivariable‐adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for intakes of foods and food groups comparing the highest to the lowest quartiles. Adolescent intakes of chicken/turkey (HR = 1.59, 95% CI: 0.97–2.60; p_trend < 0.01) and sweet baked goods (HR = 1.59, 95% CI: 1.09–2.34; p_trend = 0.04) were positively associated with thyroid cancer risk, while intake of butter/margarine was inversely associated with risk (HR = 0.64, 95% CI: 0.44–0.91; p_trend < 0.02). Similar to adolescent diet, mid‐life intake of sweet baked goods was nonsignificantly associated with an increased risk of thyroid cancer (HR = 1.39, 95% CI: 0.96–2.00; p_trend = 0.11), but intake of butter/margarine was inversely associated with risk (HR = 0.66, 95% CI: 0.46–0.95; p_trend = 0.03). Among men, higher adolescent consumption of canned tuna was positively associated with risk of thyroid cancer (HR = 1.69, 95% CI: 1.01–2.83; p_trend = 0.03), and greater mid‐life intake of broccoli was associated with a twofold increased risk (HR = 2.13, 95% CI: 1.13–3.99; p_trend < 0.01). This large prospective study suggests that several components of the adolescent and mid‐life diet, including iodine‐rich foods and goitrogens, may influence thyroid cancer risk.     

Survival of patients with initially unresectable colorectal liver metastases treated with FOLFOX/cetuximab or FOLFIRI/cetuximab in a multidisciplinary concept (CELIM study)

BackgroundInitially, unresectable colorectal liver metastases can be resected after response to chemotherapy. While cetuximab has been shown to increase response and resection rates, the survival outcome for this conversion strategy needs further evaluation.Patients and methodsPatients with technically unresectable and/or ≥5 liver metastases were treated with FOLFOX/cetuximab (arm A) or FOLFIRI/cetuximab (arm B) and evaluated with regard to resectability every 2 months. Tumour response and secondary resection data have been reported previously. A final analysis of overall survival (OS) and progression-free survival (PFS) was carried out in December 2012.ResultsBetween December 2004 and March 2008, 56 patients were randomised to arm A, 55 to arm B. The median OS was 35.7 [95% confidence interval (CI) 27.2–44.2] months [arm A: 35.8 (95% CI 28.1–43.6), arm B: 29.0 (95% CI 16.0–41.9) months, HR 1.03 (95% CI 0.66–1.61), P = 0.9]. The median PFS was 10.8 (95% CI 9.3–12.2) months [arm A: 11.2 (95% CI 7.2–15.3), arm B: 10.5 (95% CI 8.9–12.2) months, HR 1.18 (95% CI 0.79–1.74), P = 0.4]. Patients who underwent R0 resection (n = 36) achieved a better median OS [53.9 (95% CI 35.9–71.9) months] than those who did not [21.9 (95% CI 17.1–26.7) months, P < 0.001]. The median disease-free survival for R0 resected patients was 9.9 (95% CI 5.8–14.0) months, and the 5-year OS rate was 46.2% (95% CI 29.5% to 62.9%).ConclusionsThis study confirms a favourable long-term survival for patients with initially sub-optimal or unresectable colorectal liver metastases who respond to conversion therapy and undergo secondary resection. Both FOLFOX/FOLFIRI plus cetuximab, appear to be appropriate regimens for ‘conversion’ treatment in patients with K-RAS codon 12/13/61 wild-type tumours. Thus, liver surgery can be considered curative or alternatively as an additional ‘line of therapy’ in those patients who are not cured.Clinical Trial NumberNCT00153998, www.clinicaltrials.gov.     

β-Blocker usage and colorectal cancer mortality: a nested case–control study in the UK Clinical Practice Research Datalink cohort

BackgroundEpidemiological and laboratory studies suggest that β-blockers may reduce cancer progression in various cancer sites. The aim of this study was to conduct the first epidemiological investigation of the effect of post-diagnostic β-blocker usage on colorectal cancer-specific mortality in a large population-based colorectal cancer patient cohort.Patients and methods: A nested case–control analysis was conducted within a cohort of 4794 colorectal cancer patients diagnosed between 1998 and 2007. Patients were identified from the UK Clinical Practice Research Datalink and confirmed using cancer registry data. Patients with a colorectal cancer- specific death (data from the Office of National Statistics death registration system) were matched to five controls. Conditional logistic regression was applied to calculate odds ratios (OR) and 95% confidence intervals (95% CIs) according to β-blocker usage (data from GP-prescribing records).ResultsPost-diagnostic β-blocker use was identified in 21.4% of 1559 colorectal cancer-specific deaths and 23.7% of their 7531 matched controls, with little evidence of an association (OR = 0.89 95% CI 0.78–1.02). Similar associations were found when analysing drug frequency, β-blocker type or specific drugs such as propranolol. There was some evidence of a weak reduction in all-cause mortality in β-blocker users (adjusted OR = 0.88; 95% CI 0.77–1.00; P = 0.04) which was in part due to the marked effect of atenolol on cardiovascular mortality (adjusted OR = 0.62; 95% CI 0.40–0.97; P = 0.04).ConclusionsIn this novel, large UK population-based cohort of colorectal cancer patients, there was no evidence of an association between post-diagnostic β-blocker use and colorectal cancer-specific mortality.Clinical Trials numberNCT00888797.