Dietary intake of B vitamins and methionine and breast cancer risk

Purpose

We investigated prospectively the relationship between dietary intakes of methionine and B vitamins associated with one-carbon metabolism and breast cancer risk, including modification by age, hormone receptor status and alcohol consumption. Interactions between different B vitamins and methionine were also examined.

Methods

During follow-up of 20,756 women from the Melbourne Collaborative Cohort Study for an average of 16 years, we ascertained 936 incident breast cancers. Dietary intakes were estimated using a 121-item food frequency questionnaire. Hazard ratios (HR) and 95 % confidence intervals were estimated using Cox regression.

Results

We found weak evidence for an inverse association between breast cancer risk and riboflavin intake (fourth versus first quartile, HR _{Q4 vs. Q1} = 0.84 (0.69, 1.01); p _{linear trend} = 0.05) and a positive association for vitamin B12 (HR _{Q4 vs. Q1} = 1.21 (1.00, 1.46); p _{linear trend} = 0.06). We did not find any significant interactions between alcohol consumption and any of the B vitamins or methionine intake (all p _interaction > 0.17) or between methionine or folate intake and any other B vitamins (all p _interaction > 0.07). No association varied by tumor hormone receptor status (all p _homogeneity > 0.14).

Conclusions

We found weak evidence of an inverse association between breast cancer risk and riboflavin intake and a positive association with vitamin B12.     

Dietary B vitamin and methionine intakes and lung cancer risk among female never smokers in China

Purpose

B vitamins and methionine have been postulated to have potential effects on carcinogenesis; however, findings from previous epidemiologic studies on B vitamins, methionine, and lung cancer risk are inconsistent. We investigated associations of dietary intakes of B vitamins (i.e., riboflavin, niacin, vitamin B6, folate, and vitamin B12) and methionine with lung cancer risk among female never smokers.

Methods

The Shanghai Women’s Health Study, a population-based, prospective cohort study, included 74,941 women. During a median follow-up of 11.2?years, 428 incident lung cancer cases accrued among 71,267 women with no history of smoking or cancer at baseline. Baseline dietary intakes were derived from a validated, interviewer-administered food frequency questionnaire. Cancer incidence and vital status were ascertained through annual linkage to the Shanghai Cancer Registry and Shanghai Vital Statistics Registry databases and through biennial in-person follow-ups with participants. Adjusted hazard ratios (HR) and 95?% confidence intervals (CI) were calculated using Cox regression.

Results

Dietary riboflavin intake was inversely associated with lung cancer risk (HR?=?0.62; 95?% CI?=?0.43–0.89; p trend?=?0.03 for the highest quartile compared with the lowest). A higher than median intake of methionine was associated with lower risk of lung cancer (HR?=?0.78; 95?% CI?=?0.60–0.99); however, there was no dose–response relation. Intakes of other B vitamins were not associated with lung cancer risk.

Conclusions

Our study suggests that dietary riboflavin intake may be inversely associated with lung cancer risk among female never smokers, which warrants further investigation.     

Association of MTHFR C677T polymorphisms and colorectal cancer risk in Asians: evidence of 12,255 subjects

Objectives

To investigate the relationship of the MTHFR polymorphisms (C677T) and the risk of CRC by meta-analysis.

Methods

Relevant literatures concerning the association between the MTHFR C677T polymorphism and the risk of CRC were searched using the electronic database PubMed, EMBASE, Cochrane and China National Knowledge Infrastructure (CNKI). Odds ratio (ORs) and 95 % confidence intervals (CIs) were determined to assess the gene–disease association using fixed or random effect models, according to the heterogeneity among included studies.

Results

The study shows that the MTHFR 677 TT homozygous genotype significantly decreases the risk of CRC in Asians (TT vs. CC: OR = 0.82, 95 % CI 0.73–0.92; TT vs. CT: OR = 0.84, 95 % CI 0.75–0.94; TT vs. CC+TT: OR = 0.83, 95 % CI 0.75–0.93).

Conclusion

This meta-analysis indicated that the MTHFR 677 TT homozygous genotype decreased the risk of CRC in Asians, while the MTHFR 677 CT heterozygous genotype did not contribute to CRC susceptibility.     

Polymorphisms of <Emphasis Type="Italic">MTHFR</Emphasis> C677T and A1298C associated with survival in patients with colorectal cancer treated with 5-fluorouracil-based chemotherapy

Background

This study examined the association between methylenetetrahydrofolate reductase (MTHFR) polymorphisms and survival of patients with colorectal cancer (CRC) treated with 5-fluorouracil (5-FU)-based chemotherapy in Taiwan.

Methods

We genotyped MTHFR polymorphisms C677T (rs1801133) and A1298C (rs1801131) for 498 CRC patients treated with 5-FU-based chemotherapy after receiving surgery. Survival analyses on MTHFR polymorphisms were performed using log-rank test and Kaplan–Meier curve. Cox proportional hazards models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between MTHFR genotypes and survival.

Results

Overall survival (OS) was significantly longer in CRC patients with MTHFR 677 CT+TT genotypes compared with those with 677 CC genotype (HR 0.77; 95% CI 0.60–0.98). Although the MTHFR A1298C polymorphism was not associated with OS in CRC, this polymorphism was associated with significantly shorter OS in rectal cancer. Among rectal cancer patients, OS was shorter for patients with AC+CC genotypes than for those with the AA genotype (HR 1.95; 95% CI 1.35–2.83). In haplotype analysis, better OS was found for colon cancer patients carrying the MTHFR 677T-1298A haplotype (HR 0.73; 95% CI 0.55–0.97), but worse survival was linked to rectal cancer patients carrying the MTHFR 677C-1298C haplotype (HR 1.53; 95% CI 1.08–2.18).

Conclusions

Our findings suggest that MTHFR genotypes provide prognostic information for CRC patients treated with 5-FU-based chemotherapy.

     

Colorectal cancer and polymorphism of methylenetetrahydrofolate reductase (C677T) in Morocco

Introduction

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate metabolism. It is involved in the synthesis, repair, and methylation of deoxyribonucleic acid (DNA). The most frequently studied MTHFR gene polymorphism is C677T, which is involved in the pathogenesis of many diseases including cancer. This case-control study was undertaken to analyze the association of MTHFR C677T polymorphism and the risk of colorectal cancer (CRC).

Methods

We determined the genotypes and alleles of MTHFR gene in 36 patients with histological confirmed CRC (19 women and 17 men) and in 36 normal controls matched for sex without a history of cancer. DNA was isolated from peripheral blood samples, and genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

Results

In light of our results, the association of combined CT and TT genotypes and T allele was associated with an increased risk of CRC odds ratio 6.88 [95% confidence interval (CI): 2.30?C20.49, P = 0.0005), 5.91 (95% CI: 2.14?C16.34, P = 0.0006), and 2.96 (95% CI: 1.4?C6.25, P = 0.0045), respectively. TT homozygous was not a protective factor in our study with an odds ratio of 2.36 (95% CI: 0.63?C17.65, P = 0.16). Relative risk, individuals carrying at least one T allele have a 2-fold greater risk of developing CRC.

Conclusion

The MTHFR C677T gene variant was a risk factor for CRC in our population under study.     

Nutrients related to one-carbon metabolism and risk of renal cell cancer

Purpose

Folate, vitamins B6 and B12, methionine, choline, and betaine are nutrients related to one-carbon metabolism and have been hypothesized to decrease cancer risk. Few studies have evaluated dietary intakes of these nutrients in relation to renal cell cancer (RCC).

Methods

We conducted prospective follow-up studies of women in the Nurses’ Health Study and men in the Health Professionals Follow-up Study. Diet was assessed repeatedly using a validated semi-quantitative food-frequency questionnaire in both studies.

Results

During follow-up of 24 years among 77,208 women (918,891 person-years) and 22 years among 47,886 men (1,731,752 person-years), we accrued 436 cases of RCC (225 women and 211 men). Intakes of folate, vitamins B6 and B12, methionine, and betaine were not found to be related to RCC risk. Higher intake of free choline, but not other forms of choline, was associated with reduced RCC risk. The results were similar in men and women.

Conclusions

We found little evidence that higher intakes of nutrients related to one-carbon metabolism lower RCC risk. One-carbon metabolism may have little influence on renal carcinogenesis.     

Retinol, vitamins A, C, and E and breast cancer risk: a meta-analysis and meta-regression

Objective

To comprehensively summarize the associations between retinol, vitamins A, C, and E and breast cancer, and quantitatively estimate their dose?Cresponse relationships.

Methods

We searched PubMed, Embase, and Cochrane databases (from January 1982 to 15 March 2011) and the references of the relevant articles in English with sufficient information to estimate relative risk or odds ratio and the 95% confidence intervals, and comparable categories of vitamins. Two reviewers independently extracted data using a standardized form, with any discrepancy adjudicated by the third reviewer.

Results

Overall, 51 studies met the inclusion criteria. Comparing the highest with the lowest intake, total vitamin A intake reduced the breast cancer risk by 17% (pooled OR = 0.83, 95% CI: 0.78?C0.88). Further subgroup analysis based on study design did not change the significant reduction. Although the dietary vitamin A, dietary vitamin E, and total vitamin E intake all reduced breast cancer risk significantly when data from all studies were pooled, the results became nonsignificant when data from cohort studies were pooled. The significant association between total retinol intake and breast cancer in all studies became nonsignificant in case?Ccontrol studies but remain significant in cohort studies. No significant dose?Cresponse relationship was observed in the higher intake of these vitamins with reduced breast cancer risk.

Conclusions

Our results indicate that both the total intake of vitamin A and retinol could reduce breast cancer risk. However, associations between other vitamins and breast cancer seem to be limited.     

Intakes of folate,methionine, vitamin B6, and vitamin B12 with risk of esophageal and gastric cancer in a large cohort study

Background:

Nutrients in the one-carbon metabolism pathway may be involved in carcinogenesis. Few cohort studies have investigated the intakes of folate and related nutrients in relation to gastric and esophageal cancer.

Methods:

We prospectively examined the association between self-reported intakes of folate, methionine, vitamin B6, and vitamin B12 and gastric and esophageal cancer in 492 293 men and women.

Results:

We observed an elevated risk of esophageal squamous cell carcinoma with low intake of folate (relative risk (95% confidence interval): Q1 vs Q3, 1.91 (1.17, 3.10)), but no association with high intake. Folate intake was not associated with esophageal adenocarcinoma, gastric cardia adenocarcinoma, or non-cardia gastric adenocarcinoma. The intakes of methionine, vitamin B6, and vitamin B12 were not associated with esophageal and gastric cancer.

Conclusion:

Low intake of folate was associated with increased risk of esophageal squamous cell carcinoma.     

Paternal intake of folate and vitamins B6 and B12 before conception and risk of childhood acute lymphoblastic leukemia

Purpose

We investigated whether paternal dietary intake of folate before conception is associated with the risk of childhood acute lymphoblastic leukemia (ALL) in a nationwide case–control study.

Methods

Data on dietary folate intake during the 6 months before the child’s conception were collected from 285 case fathers and 595 control fathers using a dietary questionnaire. Nutrient intake was quantified using a customized computer software package based on Australian food composition databases. Data on folate intake were analyzed using unconditional logistic regression, adjusting for study-matching variables, total energy, and potentially confounding variables. In a subset of 229 cases and 420 controls, data on vitamin B6 and vitamin B12 intake were also analyzed.

Results

No consistent associations were seen with paternal dietary intake of folate or vitamin B6. Higher levels of paternal dietary vitamin B12 were appeared to be associated with an increased risk of childhood ALL, with those in the highest tertile of consumption having an OR of 1.51 (0.97, 2.36). The use of supplements containing folate and vitamins B6 or B12 was rare.

Conclusions

We did not find any biologically plausible evidence that paternal nutrition in the period leading up to conception was associated with childhood ALL. Our finding for vitamin B12 may be a chance finding, given the number of analyses performed, or be attributable to participation bias because parents with a tertiary education had the lowest level of B12 intake and tertiary education was more common among control than case parents.     

Variation in folate pathway genes and distal colorectal adenoma risk: a sigmoidoscopy-based case�Ccontrol study

Background

Folate-associated one-carbon metabolism (FOCM) is an important pathway in colorectal neoplasia risk but data on genetic variation in this pathway are largely limited to studies of single SNPs in selected genes.

Methods

We used a comprehensive tagSNP approach to study the association between genetic variation in 11 genes in the FOCM pathway and risk of incident distal colorectal adenomas in a sigmoidoscopy-based case?Ccontrol study. We included 655 cases (one or more adenomas) and 695 controls (no adenomas) recruited from one of two Kaiser Permanente clinics between 1991 and 1995. We assessed a total of 159 tagSNPs selected using Haploview Tagger as well as selected non-synonymous SNPs. We used unconditional logistic regression to model the association between SNPs and risk of distal adenomas, assuming a log-additive model.

Results

Five SNPs in the SLC19A1 (RFC1) gene: rs1051266 (G80A), rs283895, rs2236484, rs12482346, and rs2838958 were associated with adenoma risk after correction for multiple testing (all corrected p values ??0.043). The non-synonymous SLC19A1 SNP G80A interacted significantly with the MTHFR C677T genotype (interaction p value = 0.018).

Conclusion

Our data suggest that genetic variation in SLC19A1 may modify the risk of distal colorectal adenoma.     

Intakes of vitamins A, C, and E and use of multiple vitamin supplements and risk of colon cancer: a pooled analysis of prospective cohort studies

Objective

To evaluate the associations between intakes of vitamins A, C, and E and risk of colon cancer.

Methods

Using the primary data from 13 cohort studies, we estimated study- and sex-specific relative risks (RR) with Cox proportional hazards models and subsequently pooled RRs using a random effects model.

Results

Among 676,141 men and women, 5,454 colon cancer cases were identified (7–20 years of follow-up across studies). Vitamin A, C, and E intakes from food only were not associated with colon cancer risk. For intakes from food and supplements (total), the pooled multivariate RRs (95% CI) were 0.88 (0.76–1.02, >4,000 vs. ≤1,000 μg/day) for vitamin A, 0.81 (0.71–0.92, >600 vs. ≤100 mg/day) for vitamin C, and 0.78 (0.66–0.92, >200 vs. ≤6 mg/day) for vitamin E. Adjustment for total folate intake attenuated these associations, but the inverse associations with vitamins C and E remained significant. Multivitamin use was significantly inversely associated with colon cancer risk (RR = 0.88, 95% CI: 0.81–0.96).

Conclusions

Modest inverse associations with vitamin C and E intakes may be due to high correlations with folate intake, which had a similar inverse association with colon cancer. An inverse association with multivitamin use, a major source of folate and other vitamins, deserves further study.     

Methylenetetrahydrofolate reductase genetic polymorphisms and toxicity to 5-FU-based chemoradiation in rectal cancer

Background:

There is a large degree of variation in tumour response and host toxicities associated with neoadjuvant chemoradiation for rectal cancer patients. We performed a complimentary pharmacogenetic study to investigate germline polymorphisms of genes involved in 5-fluorouracil (5-FU) and irinotecan pathways and their potential association with clinical outcomes and toxicities from neoadjuvant chemoradiation in patients with rectal cancer treated in a prospective genotype-directed study.

Methods:

The germline DNA of 131 patients was genotyped for 10 variants in TYMS, MTHFR, DPYD, UGT1A1, ABCC1 and SLCO1B1 genes. Ninety-six patients were treated with 5-FU/radiotherapy (RT) and 35 received 5-FU/RT/irinotecan. Relationships between genetic variants and adverse events, tumour response, overall and disease-free survivals were assessed.

Results:

MTHFR 1298A>C and MTHFR diplotypes (for 677C>T and 1298A>C) were associated with chemoradiation-related toxicity when 5-FU was used alone. MTHFR haplotypes (677C–1298C) and diplotypes (CA–TA and TA–TA) showed, respectively, a protective and a negative effect on the incidence of severe diarrhoea or mucositis. No association was observed between genetic markers and drug response.

Conclusion:

MTHFR polymorphisms can potentially predict toxicity in patients treated with 5-FU as a single chemotherapeutic drug.     

Association between habitual dietary flavonoid and lignan intake and colorectal cancer in a Spanish case–control study (the Bellvitge Colorectal Cancer Study)

Background

Flavonoid-rich foods, such as fruits, vegetables, and tea, may have a protective effect upon colorectal cancer. However, current epidemiological evidence for a protective effect of flavonoid intake upon colorectal cancer is promising but not conclusive.

Objective

To examine the relation between dietary flavonoid and lignan intakes and the risk of colorectal cancer within a Spanish population.

Design

Data from the Bellvitge Colorectal Cancer Study, a case–control study (424 cases with incident colorectal cancer and 401 hospital-based controls), were used. A reproducible and validated food frequency questionnaire was administered in personal interviews. An ad hoc food composition database on flavonoids and lignans was compiled, mainly using data from the US Department of Agriculture and Phenol-Explorer databases. Adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) were estimated using unconditional logistic regression models.

Results

An inverse association was found between intake of total flavonoids (OR, 0.59; 95 % CI, 0.35–0.99 for the highest vs. the lowest quartile; p for trend = 0.04), lignans (OR, 0.59; 95 % CI, 0.34–0.99; p for trend = 0.03), and some individual flavonoid subgroups (flavones, proanthocyanidins) and the risk of colorectal cancer. Separate analyses by cancer site showed similar results.

Conclusions

Intake of total dietary flavonoids (particularly certain flavonoid subgroups) and lignans was inversely associated with colorectal cancer risk in a Spanish population.     

Maternal prenatal intake of one-carbon metabolism nutrients and risk of childhood leukemia

Purpose

Folate, vitamins B12 and B6, riboflavin, and methionine are critical nutrients for the one-carbon metabolism cycle involved in DNA synthesis and epigenetic processes. We examined the association between maternal intake of these nutrients before pregnancy and risk of childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) in a matched case–control study.

Methods

Maternal dietary intake and vitamin supplement use in the year before pregnancy was assessed by food frequency questionnaire for 681 ALL cases, 103 AML cases, and 1076 controls. Principal component analysis was used to construct a variable representing combined nutrient intake, and conditional logistic regression estimated the odds ratio (OR) and 95% confidence interval (CI) for the association of ALL and AML with the principal component and each nutrient.

Results

Higher maternal intake of one-carbon metabolism nutrients from food and supplements combined was associated with reduced risk of ALL (OR for one-unit change in the principal component = 0.91, CI 0.84–0.99) and possibly AML (OR for the principal component = 0.83, CI 0.66–1.04). When analyzed separately, intake of supplements high in these nutrients was associated with a reduced risk of ALL in children of Hispanic women only.

Conclusions

In conclusion, these data suggest that higher maternal intake of one-carbon metabolism nutrients may reduce risk of childhood leukemia.

     

Pharmacogenetic analysis of adjuvant FOLFOX for Korean patients with colon cancer

Purpose

Ethnic diversity of genetic polymorphism can result in individual differences in the efficacy and toxicity of cancer chemotherapy.

Methods

We analyzed 20 germline polymorphisms in 10 genes (TS, MTHFR, ERCC1, XPD, XRCC1, ABCC2, AGXT, GSTP1, GSTT1 and GSTM1) from prospectively enrolled 292 Korean patients treated with adjuvant oxaliplatin plus leucovorin plus 5-fluorouracil (FOLFOX) for colon cancer.

Results

In contrast to previous studies in Caucasians, neutropenia (grade 3–4, 60.5 %) was frequently observed, whereas only 16.4 % experienced grade 2 or more sensory neuropathy. Neutropenia was more frequent in MTHFR 677TT [adjusted odds ratio (OR) 2.32, 95 % confidence interval (CI) 1.19–4.55] and ERCC1 19007TT (adjusted OR 4.58, 95 % CI 1.20–17.40) genotypes. Patients harboring XRCC1 23885GG experienced less grade 2–4 neuropathy [adjusted OR 0.52, 95 % CI 0.27–0.99]. MTHFR 677TT (p = 0.002) and XRCC1 23885GG (p = 0.146) genotypes were also more prevalent in Koreans compared to Caucasians. TS ‘low’ genotype (adjusted HR 1.83, 95 % CI 1.003–3.34) was significantly related to shorter disease-free survival. Overall survival was not significantly different according to the polymorphisms.

Conclusions

Polymorphisms in MTHFR, XRCC1 and TS are related to toxicities and disease-free survival in patients with colon cancer. The ethnic differences in frequencies of genotypes may explain the ethnic difference in toxicity profile following adjuvant FOLFOX chemotherapy.     

The methylenetetrahydrofolate reductase (MTHFR) gene in colorectal cancer

Background and Aim: Folate deficiency predisposes to sporadic colorectal cancer (CRC). Methylenetetrahydrofolate reductase (MTHFR) is a critical folate-metabolising enzyme and a polymorphism at position 677 (C677T), is associated with reduced enzyme activity. We investigated whether this functional polymorphism modulates the risk of developing CRC. Methods: This was a retrospective case-control study, 136 unselected cases of sporadic CRC and 848 normal population controls were genotyped for the MTHFR C677T polymorphism. Tumor tissue was genotyped to assess loss of heterozygosity (LOH). Results: MTHFR CT heterozygotes had a significantly increased risk of developing CRC (53.7% of CRC cases vs 38.4% of controls), odds ratio 1.86 (95% CI 1.3–2.7, p<0.005). No increased cancer risk was observed in TT homozygotes. The MTHFR ‘T’ allele frequency was significantly higher in the cancer group (0.3713) as compared to controls (0.2900, p<0.008). LOH at the MTHFR locus was observed in 18% of informative cancers, with exclusive loss of the variant ‘T’ allele, in all cases. Conclusion: In this study of a homogenous northern European population, MTHFR CT heterozygotes had an almost two-fold increased risk of developing sporadic CRC. The exclusive pattern of MTHFR allele loss in cases of LOH, suggest that functional MTHFR activity within a tumor might play an important role in the survival and progression of a colonic neoplasm.     

Risk factors for young-onset colorectal cancer

Purpose

We investigated risk factors for colorectal cancer in early-onset cancers, to provide quantitative estimates for major selected risk factors.

Methods

We analyzed data from three Italian and Swiss case–control studies conducted between 1985 and 2009, including 329 colorectal cancer cases and 1,361 controls aged ≤45 years. We computed odds ratios (ORs) from unconditional logistic regression models, adjusted for major confounding factors.

Results

The OR of young-onset colorectal cancer was 4.50 for family history of colorectal cancer in first-degree relatives, the association being higher in subjects with affected siblings (OR 11.68) than parents (OR 3.75). The ORs of young-onset colorectal cancer were 1.56 for ≥14 drinks/week of alcohol, 1.56 for the highest tertile of processed meat, 0.40 for vegetables, 0.75 for fruit, and 0.78 for fish intake. Among micronutrients, the ORs were 0.52 for β-carotene, 0.68 for vitamin C, 0.38 for vitamin E, and 0.59 for folate. No significant associations emerged for physical activity, overweight, and diabetes.

Conclusions

This study—the largest on young-onset colorectal cancer—confirms that several recognized risk factors for colorectal cancer are also relevant determinants of young-onset colorectal cancer. Family history of colorectal cancer in particular is a stronger risk factor in young subjects, as compared to middle age and elderly ones.     

Vitamin D status and risk of non-Hodgkin lymphoma: a meta-analysis

Background

Non-Hodgkin lymphoma (NHL) is among the ten most frequent malignancies in Europe and USA. Results for vitamin D status and risk of NHL have been inconsistent.

Objective

The objective was to perform a meta-analysis to summarize the available evidence from case–control studies and cohort studies on the association of vitamin D status and the risk of NHL.

Design

We searched PubMed, ISI Web of Science, the Cochrane Library, EMBASE, and reference lists for relevant articles. Study-specific odds ratios (ORs) or relative risks and 95 % confidence intervals (CIs) were pooled using fixed-effects, random-effects, or linear regression dose-response models.

Results

Nine studies (eight case–control and one cohort studies) were included in the meta-analysis. The estimated summary OR for highest compared with lowest categories of vitamin D status was 1.03 (95 % CI 0.84, 1.26; heterogeneity I ² = 57.5 %). The subgroup analysis showed the similar results for dietary vitamin D intake group (1.07; 95 % CI 0.82, 1.40) and serum 25-hydroxyvitamin D concentration values group (1.03; 95 % CI 0.84, 1.26). The pooling ORs of NHL most common subtypes were 1.05 (0.73, 1.52), 1.00 (0.63, 1.58), 1.10 (0.56, 2.14), and 1.69 (0.68, 4.20) for diffuse large B cell lymphoma, follicular lymphoma, small lymphocytic lymphomas/chronic lymphocytic leukemia, and T cell lymphoma. The result from the linear regression dose–response model was similar (p = 0.205).

Conclusions

Higher vitamin D status does not play a protective role in risk of NHL or common NHL subtypes.     

Molecular markers of response and toxicity to FOLFOX chemotherapy in metastatic colorectal cancer

Background:

To investigate three genetic alterations (TP53 mutation, Kras mutation and microsatellite instability (MSI)) and three polymorphisms (methylene tetrahydrofolate reductase (MTHFR) C677T, excision repair cross complementing group 1 (ERCC1)-118 and X-ray repair cross complementing group 1 (XRCC1)-399) for their ability to predict response, survival and toxicity to FOLFOX first line chemotherapy in the treatment of metastatic colorectal cancer (mCRC).

Methods:

Tumour tissues from 118 mCRC patients who underwent FOLFOX treatment from three successive phase II trials were evaluated for mutations in TP53 (exons 5–8) and Kras (codons 12 and 13) and for MSI using PCR-based analysis. Genotyping for common single nucleotide polymorphisms in the MTHFR (codon 677), ERCC1 (codon 118) and XRCC1 (codon 399) genes was also carried out using PCR techniques. These genetic markers were correlated with clinical response, survival and toxicity to treatment.

Results:

Patients with the T allele of ERCC1-118 showed significantly worse progression-free survival in univariate analysis (HR=2.62; 95% CI=1.14–6.02; P=0.02). None of the genetic alterations or polymorphisms showed significant association with clinical response to FOLFOX. The MTHFR, ERCC1 and XRCC1 polymorphisms showed no associations with overall haematological, gastrointestinal or neurological toxicity to FOLFOX, although MTHFR 677 TT genotype patients showed a significantly higher incidence of grade 3 or 4 diarrhoea (26%) compared with CC or CT genotype patients (6%, P=0.02).

Conclusions:

The ERCC1-118 and MTHFR C677T polymorphisms were associated with progression and severe diarrhoea, respectively, after FOLFOX treatment in mCRC. Although our findings require confirmation in large prospective studies, they reinforce the concept that individual genetic variation may allow personalized selection of chemotherapy to optimize clinical outcomes.     

Red and processed meat intake and risk of colorectal adenomas: a systematic review and meta-analysis of epidemiological studies

Background

Current evidence indicates that red and processed meat intake increases the risk of colorectal cancer; however, the association with colorectal adenomas is unclear.

Objective

To conduct a systematic review and meta-analysis of epidemiological studies of red and processed meat intake and risk of colorectal adenomas as part of the Continuous Update Project of the World Cancer Research Fund.

Design

PubMed and several other databases were searched for relevant studies from their inception up to 31 December 2011. Summary relative risks (RRs) were estimated using a random effects model.

Results

Nineteen case–control studies and seven prospective studies were included in the analyses. The summary RR per 100 g/day of red meat was 1.27 (95 % CI 1.16–1.40, I ² = 5 %, n = 16) for all studies combined, 1.20 (95 % CI 1.06–1.36, I ² = 0 %, n = 6) for prospective studies, and 1.34 (95 % CI 1.12–1.59, I ² = 31 %, n = 10) for case–control studies. The summary RR per 50 g/day of processed meat intake was 1.29 (95 % CI 1.10–1.53, I ² = 27 %, n = 10) for all studies combined, 1.45 (95 % CI 1.10–1.90, I ² = 0 %, n = 2) for prospective studies, and 1.23 (95 % CI 0.99–1.52, I ² = 37 %, n = 8) for case–control studies. There was evidence of a nonlinear association between red meat (p _nonlinearity < 0.001) and processed meat (p _nonlinearity = 0.01) intake and colorectal adenoma risk.

Conclusion

These results indicate an elevated risk of colorectal adenomas with intake of red and processed meat, but further prospective studies are warranted.