Polymorphisms in one-carbon metabolism and trans-sulfuration pathway genes and susceptibility to bladder cancer

We have previously reported significant inverse associations between bladder cancer risk and dietary intake of vitamins B2, B6, B12, folate and protein in a hospital-based bladder cancer case-control study conducted in Spain (1,150 cases;1,149 controls). Because these dietary factors are involved in the one-carbon metabolism pathway, we evaluated associations between bladder cancer risk and 33 single nucleotide polymorphisms (SNPs) in 8 genes (CBS, CTH, MTHFR, MTR, MTRR, SHMT1, SLC19A1 and TYMS) and interactions with dietary variables involved in this pathway. Two SNPs in the CTH gene were significantly associated with bladder cancer risk. OR (95% CI) for heterozygous and the homozygous variants compared to homozygous wild-type individuals were: 1.37 (1.04-1.80) IVS3-66 A > C and 1.22 (1.02-1.45) IVS10-430 C > T. Because the CTH gene is important for glutathione synthesis, we examined interactions with the GSTM1 gene, which codes for glutathione S-transferase muu. Increased risk for individuals with the IVS10-430 CT or TT genotype was limited to those with the GSTM1 null genotype (p-interaction = 0.02). No other SNPs were associated with risk of bladder cancer. These findings suggest that common genetic variants in the one-carbon pathway may not play an important role in the etiology of bladder cancer. However, our results provide some evidence that variation in glutathione synthesis may contribute to risk, particularly among individuals who carry a deletion in GSTM1. Additional work is needed to comprehensively evaluate genomic variation in CTH and related genes in the trans-sulfuration pathway and bladder cancer risk.     

Folate intake, methylenetetrahydrofolate reductase polymorphisms, and risk of esophageal cancer

Aim: Genetic and environmental factors may play roles in the pathogenesis of esophageal cancer and susceptibility may be modified by functional polymorphisms in folate metabolic genes, such as methylenetetrahydrofolate reductase (MTHFR). We here evaluated associations of the MTHFR C677T polymorphism and folate intake with esophageal cancer. Methods: A matched hospital-based case-control study with 155 esophageal cancer and 310 non-cancer controls was conducted in a Chinese population with gene-environment interactions evaluated between the MTHFR C667T polymorphism and drinking and smoking, as well as folate intake. Results: Individuals carrying MTHFR 667CT [adjusted odds ratio (OR), 1.95; 95% confidence interval (CI), 1.23-2.62] and TT [adjusted odds ratio (OR), 3.36; 95% confidence interval (CI), 1.46-8.74] had significantly increased esophageal cancer risk compared with those with MTHFR 667CC genotype. Folate intake was seen to have non-significant preventive effect. In former, moderate and heavy drinkers, a high esophageal cancer risk was observed for those with an MTHFR 677T allele genotype [ORs: 5.0(1.29-18.88), 3.70(1.83-7.66) and 5.77(2.11-15.72), respectively]. Significant interaction was found for moderate-heavy drinking and the MTHFR 677T allele genotype for esophageal cancer risk (p<0.05). Significant increased risk was also found in moderate and heavy smokers with the two genotypes [ORs: 3.58(1.64-7.80) and 4.51(1.15-17.78), respectively]. High folate intake and MTHFR 677TT was associated with a non-significant tendency for decreased esophageal cancer risk. Conclusion: Our finding supports the hypothesis that MTHFR C667T polymorphisms play a role in pathogenesis of esophageal cancer in the Chinese population.     

Dietary intake of fruit and vegetable and lung cancer risk: a case-control study in Harbin, northeast China.

BACKGROUND: We studied the relationship between dietary intake of vegetables and fruit and lung cancer risk in Harbin, Heilongjiang province, northeast China, an area with a very high baseline risk of lung cancer in both sexes. PATIENTS AND METHODS: We used data from a case-control study, conducted from 1987 to 1990, among 218 cases with incident, histologically confirmed lung cancer and 436 controls admitted to the same hospitals as cases with non-neoplastic, non-lung diseases unrelated to smoking and other potential risk factors for lung cancer. RESULTS: Compared with the lowest tertile of intake of vegetables, fruit or both, the multivariate odds ratios (ORs) for the highest tertile of intake were 0.39 [95% confidence interval (CI) 0.25-0.62], 0.73 (95% CI 0.48-1.11) and 0.40 (95% CI 0.25-0.63), respectively. In particular, high intake of Chinese cabbage (OR = 0.53), chives (OR = 0 .54), carrots (OR = 0.51) and celery (OR = 0.40) was inversely associated with lung cancer. The OR was more than six-fold elevated for smokers reporting low intake of vegetables, and more than four-fold elevated for smokers reporting low intake of fruit, as compared with never smokers reporting high intake of these items. CONCLUSION: In agreement with previous studies, we found an inverse relation between vegetable and fruit intake and lung cancer risk in both strata of current and never smokers.     

Folate intake and the risk of oral cavity and pharyngeal cancer: A pooled analysis within the International Head and Neck Cancer Epidemiology Consortium

There are suggestions of an inverse association between folate intake and serum folate levels and the risk of oral cavity and pharyngeal cancers (OPCs), but most studies are limited in sample size, with only few reporting information on the source of dietary folate. Our study aims to investigate the association between folate intake and the risk of OPC within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium. We analyzed pooled individual‐level data from ten case–control studies participating in the INHANCE consortium, including 5,127 cases and 13,249 controls. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were estimated for the associations between total folate intake (natural, fortification and supplementation) and natural folate only, and OPC risk. We found an inverse association between total folate intake and overall OPC risk (the adjusted OR for the highest vs. the lowest quintile was 0.65, 95% CI: 0.43–0.99), with a stronger association for oral cavity (OR = 0.57, 95% CI: 0.43–0.75). A similar inverse association, though somewhat weaker, was observed for folate intake from natural sources only in oral cavity cancer (OR = 0.64, 95% CI: 0.45–0.91). The highest OPC risk was observed in heavy alcohol drinkers with low folate intake as compared to never/light drinkers with high folate (OR = 4.05, 95% CI: 3.43–4.79); the attributable proportion (AP) owing to interaction was 11.1% (95% CI: 1.4–20.8%). Lastly, we reported an OR of 2.73 (95% CI:2.34‐3.19) for those ever tobacco users with low folate intake, compared with nevere tobacco users and high folate intake (AP of interaction =10.6%, 95% CI: 0.41‐20.8%). Our project of a large pool of case–control studies supports a protective effect of total folate intake on OPC risk.     

Folate intake and colorectal cancer risk: a meta-analytical approach

Adequate consumption of folate may reduce the risk of colorectal cancer. We performed a meta-analysis of 7 cohort and 9 case-control studies that examined the association between folate consumption and colorectal cancer risk. In cohort studies, the association between folate consumption and colorectal cancer risk was stronger for dietary folate (folate from foods alone; relative risk for high vs. low intake = 0.75; 95% CI = 0.64-0.89) than for total folate (folate from foods and supplements; relative risk for high vs. low intake = 0.95; 95% CI = 0.81-1.11) and there was no significant heterogeneity between studies. There was significant heterogeneity between case-control studies. These results offer some support for the hypothesis that folate has a small protective effect against colorectal cancer but confounding by other dietary factors cannot be ruled out.     

Folate intake and risk of oral and pharyngeal cancer.

BACKGROUND: Diet has been recognised as having a role in the aetiology of oral and pharyngeal cancer, and dietary factors may account for 10-15% of cases in Europe. Folate deficiency has been linked to risk of several cancers, but has not been studied adequately with respect to oral cancer. PATIENTS AND METHODS: This case-control study, conducted in Italy and French-speaking Switzerland, included 749 patients with incident cancer of the oral cavity and pharynx, and 1772 hospital controls with acute, non-neoplastic conditions. The interviews used a validated food frequency questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using multiple logistic regression. RESULTS: The ORs were 0.68 (95% CI 0.52-0.88) for the intermediate tertile and 0.53 (95% CI 0.40-0.69) for the highest tertile of dietary folate intake, compared with the lowest tertile. No heterogeneity was found in strata of gender, age, methionine intake or alcohol consumption. The combined OR for low-folate and high-alcohol intake versus high-folate and low-alcohol intake was 22.3 (95% CI 13.1-38). CONCLUSIONS: Our study supports a protective role of folate against oral and pharyngeal carcinogenesis. Compared with low folate intake, a consistent reduction in risk was already observed from intermediate levels of intake, suggesting that cancer risk may be related to relative folate deficiency.     

B-vitamin intake,metabolic genes,and colorectal cancer risk (United States)

Objective: This population-based case–control study was designed to investigate the interrelationships between polymorphisms in the methylenetetrahydrofolate (MTHFR C677T and A1298C) gene and other genes (MTR A2756G; MTRR A66G and CBS 844ins68), intake of B-vitamins and colorectal cancer risk (CRC). Methods: We interviewed 727 CRC cases of Japanese, Caucasian, or Native Hawaiian origin and 727 controls matched on sex, age, and ethnicity. Results: Compared to the homozygous wild-type genotype, the odds ratios for subjects with one or two MTHFR 677T variant alleles were 0.8 (0.6–1.1) and 0.7 (0.5–1.1), respectively (p for gene–dosage effect: 0.04). The TT genotype was associated with a 50–60% decrease in CRC risk among subjects with high intake of folate or vitamin B6, compared to those with the CC genotype and low levels of intake. The MTHFR 1298C and CBS8 44ins68 variant alleles were also found to be weakly protective against CRC and to act jointly with the 677T allele. Conclusions: This study provides additional evidence for a decreased CRC risk for subjects with the MTHFR 677T allele, particularly at high levels of folate and vitamin B6 intake. Our data also suggest that the relationships between CRC and the MTHFR A1298C and CBS 844ins68 polymorphisms warrant further study.     

Iron intake,oxidative stress-related genes and breast cancer risk

Iron has been suggested to contribute to breast cancer development through oxidative stress generation. Our study investigated associations between iron intake and breast cancer risk, overall and by menopausal and estrogen receptor/progesterone receptor (ER/PR) status, and modification by oxidative stress-related genetic polymorphisms (MnSOD, GSTM1 and GSTT1). A population-based case–control study (3,030 cases and 3,402 controls) was conducted in Ontario, Canada. Iron intake (total, dietary, supplemental, heme, nonheme) was assessed using a validated food frequency questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were estimated from multivariable logistic regression models. Interactions between iron intake and genotypes were assessed among 1,696 cases and 1,761 controls providing DNA. Overall, no associations were observed between iron intake and breast cancer risk. Among premenopausal women, total, dietary and dietary nonheme iron were positively associated with ER–/PR– breast cancer risk (all p_trend < 0.05). Among postmenopausal women, supplemental iron was associated with reduced breast cancer risk (OR_{>18 vs. 0 mg/day} = 0.68, 95% CI: 0.51–0.91), and dietary heme iron was associated with an increased risk, particularly the ER–/PR– subtype (OR_{highest vs. lowest quintile} = 1.69, 95% CI: 1.16–2.47; p_trend = 0.02). Furthermore, GSTT1 and combined GSTM1/GSTT1 polymorphisms modified some of the associations. For example, higher dietary iron was most strongly associated with increased breast cancer risk among women with GSTT1 deletion or GSTM1/GSTT1 double deletions (p_interaction < 0.05). Findings suggest that iron intake may have different effects on breast cancer risk according to menopausal and hormone receptor status, as well as genotypes affecting antioxidant capacity.     

MTHFR polymorphisms, folate intake and carcinogen DNA adducts in the lung

The methylenetetrahydrofolate reductase (MTHFR) genes and folate in one-carbon metabolism are essential for DNA methylation and synthesis. However, their role in carcinogen DNA damage in target lung tissue, a dosimeter for cancer risk, is not known. Our study aimed to investigate the association between genetic and nutritional one-carbon metabolism factors and DNA adducts in target lung. Data on 135 lung cancer cases from the Massachusetts General Hospital were studied. Genotyping was completed for MTHFR C677T (rs1801133) and A1298C (rs1801131). Information on dietary intake for one-carbon related micronutrients, folate and other B vitamin was derived from a validated food frequency questionnaire. DNA adducts in lung were measured by (32) P-postlabeling. After adjusting for potential confounders, DNA adduct levels in lung significantly increased by 69.2% [95% confidence interval (CI), 5.5% to 171.5%] for the MTHFR 1298AC+CC genotype. The high risk group, combining the A1298C (AC+CC) plus C677T (CT+TT) genotypes, had significantly enhanced levels of lung adducts by 210.7% (95% CI, 21.4% to 695.2%) in contrast to the A1298C (AA) plus C677T (CC) genotypes. Elevation of DNA adduct was pronounced-111.3% (95% CI, -3.0 to 360.5%) among 1298AC+CC patients, who consumed the lowest level of folate intake as compared to 1298AA individuals with highest tertile of intake. These results indicate that DNA adducts levels are influenced by MTHFR polymorphisms and low folate consumption, suggesting an important role of genetic and nutritional factors in protecting DNA damage from lung carcinogen in at-risk populations.     

Genetic polymorphisms in alcohol metabolism, alcohol intake and the risk of stomach cancer in Warsaw, Poland

Genetic variations increasing blood levels of acetaldehyde, the first metabolite of alcohol, refrain their carriers from drinking alcohol but may also put them at increased risk of cancer because of the mutagenic and carcinogenic effect of acetaldehyde. In a population-based study of 305 cases and 428 controls in Warsaw, Poland, we evaluated the effect of polymorphisms in alcohol metabolizing genes, including ADH1B (Ex9+5C>T, Ex3+23A>G, Ex3+58A>T and Ex9+77A>G), ADH1C (Ex8-56A>G and Ex6-14G>A) and ALDH2 (Ex1+82A>G), on levels of alcohol drinking and susceptibility of stomach cancer. We found that among control subjects frequency of alcohol drinking varied by alcohol metabolizing genotype. In particular, the weekly consumption of individuals carrying the AA, GA and GG genotypes of ALDH2 Ex1+82A>G polymorphism were 3.75, 2.26 and 1.53 drinks, respectively (p=0.04). However, none of the assessed polymorphisms in these 3 genes had a measurable effect on stomach cancer risk. When stratified by ALDH2 Ex1+82A>G polymorphism, alcohol-related increases in stomach cancer risk were restricted to individuals with the AG/GG genotypes, with a more than 2-fold risk among daily drinkers (OR=2.63, 95% CI=1.00-6.88) and 3-fold risk (OR=3.66, 95% CI=1.19-11.24) among those with 40 or more drink-years. In summary, our results suggested that the ALDH2 Ex1+82 G allele may be functionally deficient in eliminating acetaldehyde and discourage alcohol drinking. Furthermore, heavy drinkers of alcohol who were genetically prone to accumulate acetaldehyde may face an increased risk of stomach cancer.     

Folate, vitamin B(6) , vitamin B(12) , methionine and alcohol intake in relation to ovarian cancer risk

Folate, methionine, vitamin B(6) and vitamin B(12) may influence carcinogenesis due to their roles in the one-carbon metabolism pathway, which is critical for DNA synthesis, methylation and repair. Low intake of these nutrients has been associated with an increased risk of breast, colon and endometrial cancers. Previous studies that have examined the relation between these nutrients and ovarian cancer risk have been inconsistent and have had limited power to examine the relation by histologic subtype. We investigated the association between folate, methionine, vitamin B(6) , vitamin B(12) and alcohol among 1910 women with ovarian cancer and 1989 controls from a case-control study conducted in eastern Massachusetts and New Hampshire from 1992 to 2008. Diet was assessed via food frequency questionnaire. Participants were asked to recall diet one-year before diagnosis or interview. Logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (95% CIs). We also examined whether the associations varied by ovarian cancer histologies using polytomous logistic regression. We observed an inverse association between dietary vitamin B(6) (covariate-adjusted OR = 0.76, 95% CI 0.64-0.92; p(trend) = 0.002) and methionine intake (covariate-adjusted OR = 0.72, 95% CI = 0.60-0.87; p(trend) < 0.001) and ovarian cancer risk comparing the highest to lowest quartile. The association with dietary vitamin B(6) was strongest for serous borderline (covariate-adjusted OR = 0.49, 95% CI = 0.32-0.77; p(trend) = 0.001) and serous invasive (covariate-adjusted OR = 0.74, 95% CI = 0.58-0.94; p(trend) = 0.012) subtypes. Overall, we observed no significant association between folate and ovarian cancer risk. One-carbon metabolism related nutrients, especially vitamin B(6) and methionine, may lower ovarian cancer risk.     

Carcinogen metabolism genes, red meat and poultry intake, and colorectal cancer risk

Diets high in red meat are established risk factors for colorectal cancer (CRC). Carcinogenic compounds generated during meat cooking have been implicated as causal agents. We conducted a family-based case-control study to investigate the association between polymorphisms in carcinogen metabolism genes (CYP1A2 -154A>C, CYP1B1 Leu432Val, CYP2E1 -1054C>T, GSTP1 Ile105Val, PTGS2 5UTR -765, EPHX1 Tyr113His, NAT2 Ile114Thr, NAT2 Arg197Gln and NAT2 Gly286Glu) and CRC risk. We tested for gene-environment interactions using case-only analyses (N = 577) and compared statistically significant results to those obtained using case-unaffected sibling comparisons (N = 307 sibships). Our results suggested that CYP1A2 -154A>C might modify the association between intake of red meat cooked using high temperature methods and well done on the inside and CRC risk (case-only interaction OR = 1.53; 95% CI = 1.19-1.97; p = 0.0008) and the association between intake of red meat heavily browned on the outside and rectal cancer risk (case-only interaction OR = 0.65; 95% CI = 0.48-0.86; p = 0.003). We also found that GSTP1 Ile105Val might modify the association between intake of poultry cooked with high temperature methods and CRC risk (p = 0.0035), a finding that was stronger among rectal cancer cases. Our results support a role for heterocyclic amines that form in red meat as a potential explanation for the observed association between diets high in red meat and CRC. Our findings also suggest a possible role for diets high in poultry cooked at high temperatures in CRC risk.     

Dietary folate intake and pancreatic cancer risk: Results from the European prospective investigation into cancer and nutrition

Pancreatic cancer (PC) has an exceptionally low survival rate and primary prevention strategies are limited. Folate plays an important role in one-carbon metabolism and has been associated with the risk of several cancers, but not consistently with PC risk. We aimed to investigate the association between dietary folate intake and PC risk, using the standardised folate database across 10 European countries. A total of 477,206 participants were followed up for 11 years, during which 865 incident primary PC cases were recorded. Folate intake was energy-adjusted using the residual method. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. In multivariable analyses stratified by age, sex, study centre and adjusted for energy intake, smoking status, BMI, educational level, diabetes status, supplement use and dietary fibre intake, we found no significant association between folate intake and PC risk: the HR of PC risk for those in the highest quartile of folate intake (≥353 μg/day) compared to the lowest (<241 μg/day) was 0.81 (95% CI: 0.51, 1.31; p_trend = 0.38). In current smokers, a positive trend was observed in PC risk across folate quartiles [HR = 4.42 (95% CI: 1.05, 18.62) for ≥353 μg/day vs. <241 μg/day, p_trend = 0.01]. Nonetheless, there was no significant interaction between smoking and dietary folate intake (p_interaction = 0.99). We found no association between dietary folate intake and PC risk in this large European study.     

Dietary intake of nutrients involved in one‐carbon metabolism and risk of urothelial cell carcinoma: A prospective cohort study

Nutrients involved in one‐carbon metabolism may play a role in carcinogenesis through DNA replication, repair and methylation mechanisms. Most studies on urothelial cell carcinoma (UCC) have focused on folate. We sought to examine the association between B‐group vitamins and methionine intake and UCC risk, overall and by subtype, and to test whether these associations are different for population subgroups whose nutritional status may be compromised. We followed participants in the Melbourne Collaborative Cohort Study (N = 41,513) for over 20 years and observed 500 UCC cases (89% originating in the bladder; superficial: 279, invasive: 221). Energy‐adjusted dietary intakes of B vitamins (B1, B2, B3, B5, B6, B8, B9 and B12) and methionine were estimated from a 121‐item food frequency questionnaire administered at baseline (1990–1994), using the residuals method. We used Cox regression models to compute hazard ratios (HRs) of UCC risk per standard deviation (SD) of log‐transformed nutrient intakes and 95% confidence intervals, adjusted for potential confounders. We investigated associations by tumor subtype, and tested interactions with sex, country of birth, smoking and alcohol drinking. The risk of UCC appeared not to be associated with intake of B‐group vitamins or methionine, and findings were consistent across tumor subtypes and across demographic and lifestyle characteristics of the participants. A potential interaction between vitamin B1 and alcohol drinking was observed (all participants: HR per 1 SD = 0.99 (0.91–1.09), never drinkers: HR = 0.81 (0.69–0.97), p‐interaction = 0.02), which needs to be confirmed by other studies. Our findings do not indicate that dietary intake of nutrients involved in one‐carbon metabolism are associated with UCC risk.     

Fluid intake,genetic variants of UDP-glucuronosyltransferases,and bladder cancer risk

Background:

Results of studies of fluid consumption and its association with bladder cancer have been inconsistent. Few studies have considered modification effects from genetic variants that may interact with the type of consumed fluids. UDP-glucuronosyltransferases (UGTs), which are membrane-bound conjugating enzymes, catalyse the transformation of hydrophobic substrates to more water-soluble glucuronides to facilitate renal or biliary excretion. Whether genetic variants in UGTs could modulate the association between fluid intake and bladder cancer has not been studied.

Methods:

We conducted a case–control study with 1007 patients with histopathologically confirmed bladder cancer and 1299 healthy matched controls. Fluid intake and epidemiologic data were collected via in-person interview. Multivariate unconditional logistic regression was used to estimate odds ratios (ORs) and the 95% confidence intervals (95% CI).

Results:

After adjustment for potential confounders, high quantity of total fluid intake (⩾2789 vs <1696 ml per day) conferred a 41% increased risk of bladder cancer (OR=1.41; 95% CI=1.10–1.81). Specific fluids such as regular soft drinks and decaffeinated coffee were also associated with increased risks, whereas tea, wine, and liquor were associated with decreased risks. Among 83 single-nucleotide polymorphisms in the UGT gene family, 18 were significantly associated with bladder cancer risk. The most significant one was rs7571337, with the variant genotype conferring a 29% reduction in risk (OR=0.71; 95% CI=0.56–0.90).

Conclusions:

Total and specific fluid intakes are associated with bladder cancer risk in the study population and that genetic variants of UGT genes could modulate the effects. These results facilitate identification of high-risk individuals and have important implications in bladder cancer prevention.     

Variations in sex hormone metabolism genes, postmenopausal hormone therapy and risk of endometrial cancer

We investigated whether variants in sex steroid hormone metabolism genes modify the effect of hormone therapy (HT) on endometrial cancer risk in postmenopausal non-Hispanic white women. A nested case-control study was conducted within the California Teachers Study (CTS). We genotyped htSNPs in six genes involved in the hormone metabolism in 286 endometrial cancer cases and 488 controls. Odds ratio (OR) and 95% confidence interval (CI) were estimated for each haplotype using unconditional logistic regression, adjusting for age. The strongest interaction was observed between duration of estrogen therapy (ET) use and haplotype 1A in CYP11A1 (p(interaction) = 0.0027; p(interaction) = 0.010 after correcting for multiple testing within each gene). The OR for endometrial cancer per copy of haplotype 1A was 2.00 (95% CI: 1.05-3.96) for long-term ET users and 0.90 (95% CI: 0.69-1.18) for never users. The most significant interaction with estrogen-progestin therapy (EPT) was found for two haplotypes on CYP19A1 and EPT use (haplotype 4A, p(interaction) = 0.024 and haplotype 3B, p(interaction) = 0.043). However, neither this interaction, nor the ET or EPT interactions for any other genes, was statistically significant after correction for multiple testing. Variations in CYP11A1 may modify the effect of ET use on risk of postmenopausal endometrial cancer; however, larger studies are needed to explore these findings further.     

Fibre intake and prostate cancer risk

Dietary fibre has been reported to protect from several neoplasms, but the issue remains controversial. No previous study considered in depth the topic of fibres and prostate cancer. A multicentre case-control study was conducted in Italy from 1991 to 2002, including 1,294 men with incident, histologically confirmed prostate cancer and 1,451 controls admitted to the same network of hospitals as cases with acute nonmalignant conditions. Multivariate odds ratios (OR) and 95% confidence intervals (CI) were obtained after allowance for major identified confounding factors, including total energy intake. Compared to the lowest quintile, the OR of prostate cancer for the highest quintile of total fibre intake was 0.93 (95% CI 0.71-1.22). The risk was inversely related with soluble fibre (OR = 0.89, 95% CI 0.78-1.02, for a difference between 80th and 20th percentile), cellulose (OR = 0.88, 95% CI 0.78-1.01) and vegetable fibre (OR = 0.82, 95% CI 0.73-0.93). These relationships were consistent across strata of age, family history of prostate cancer, body mass index and education. Vegetable fibres appear, therefore, to have a favourable association with prostate cancer risk.     

Coffee intake, variants in genes involved in caffeine metabolism, and the risk of epithelial ovarian cancer

We evaluated whether genetic variability, as well as menopausal status, modify the association between coffee intake and risk of ovarian cancer. Risk factor information and biologic specimens from three large epidemiological studies, the Nurses’ Health Study (NHS), NHSII, and the New England based Case-Control Study of ovarian cancer (NECC) were pooled resulting in 1,354 ovarian cancer cases and 1,851 controls for analysis. Odds ratios (ORs) and 95% confidence intervals (CI) were estimated using conditional (NHS/NHSII) and unconditional (NECC) logistic regression. Coffee consumption was not associated with overall risk (OR = 0.99; 95% CI 0.77–1.28); however, there was a suggested increased risk of ovarian cancer among premenopausal women in the NECC only and an inverse association among postmenopausal women. Carrying one or both of the variant CYP19013 A or CYP19027 G alleles was associated with an 18% increased (P for trend = 0.02) and 15% decreased (P for trend = 0.05) risk of ovarian cancer, respectively. Variation in CYP1A1, CYP1A2, or CYP2A6 did not explain the inconsistent reports of coffee intake and risk. Furthermore, we did not observe any clear gene–environment interactions between caffeine metabolizing genes and ovarian cancer. Future studies evaluating mechanisms by which coffee mediates this relationship are warranted.

Relationship between vegetable and carotene intake and risk of prostate cancer: the JACC study

Background:

We examined the associations of intakes of vegetables and carotenes with risk of prostate cancer in Japanese.

Methods:

A total of 15 471 Japanese men participating in the Japan Collaborative Cohort study completed a questionnaire including food intake. Of them, 143 incident prostate cancers were documented. We examined the associations stated above by using Cox proportional hazard model.

Results:

Vegetable intake was not associated with the risk of prostate cancer, but so was dietary alpha-carotene intake. The multivariable hazard ratio (95%CI) in the secondary highest and highest quintiles of alpha-carotene intake was 0.50 (0.26–0.98) (P=0.043) and 0.46 (0.22–0.97) (P=0.041) (P for trend=0.224), respectively. Beta-carotene intake was not associated with the risk of prostate cancer.

Conclusion:

Alpha-carotene intake was associated with lower risk of prostate cancer among Japanese.