Prospective Study of Dietary Phytoestrogen Intake and the Risk of Colorectal Cancer.

Dietary phytoestrogen intake has been inversely associated with the risk of prostate and breast cancer and might also affect the risk of colorectal cancer. We evaluated the associations between dietary lignan intake, dietary isoflavonoid intake, dietary coumestrol intake, and dietary enterolignans and equol intake, and risk of colorectal cancer. Data from the Women's Lifestyle and Health (WLH) Cohort study was used. The WLH study is a prospective population-based cohort study including 48,268 Swedish women aged 30-49 years at the time of enrolment in 1991-92. Follow-up for colorectal cancer incidence, death, and emigration until the end of 2010 was performed through record linkage to the Swedish Cancer Registry and Total Population Register. During follow-up 206 incident colorectal cancer cases were identified. Cox proportional hazards models were fitted to estimate adjusted risk ratios with 95% confidence intervals. We found no statistically significant association between the intake of dietary lignans, dietary isoflavonoids, coumestrol, or enterolignans and equol, and risk of colorectal cancer. We found no association between dietary phytoestrogen intake and the risk of colorectal cancer. However, since the number of cancer cases was small, our results need to be confirmed. Future studies should investigate colon and rectal cancer separately.

Intrusive thoughts and quality of life among men with prostate cancer before and three months after surgery.

BACKGROUND: Sudden, unwelcome and repetitive thoughts about a traumatic event--intrusive thoughts--could relate to how men assess their quality of life after prostate-cancer diagnosis. We aimed to study the prevalence of intrusive thoughts about prostate cancer and their association with quality-of-life outcomes before and after radical prostatectomy. METHODS: During the first year of the LAPPRO-trial, 971 men scheduled for radical prostatectomy were prospectively included from 14 urological centers in Sweden. Of those, 833 men responded to two consecutive study-specific questionnaires before and three months after surgery (participation rate 86%). The association of intrusive thoughts with three quality-of-life outcomes, i.e. self-assessed quality of life, depressive mood and waking up with anxiety was estimated by prevalence ratios that were calculated, together with a 95% confidence interval, at the same time-point as well as over time. Fisher's exact-test was used to analyze differences between respondents and non-respondents. Wilcoxon signed-ranks and Cochran-Armitage trend tests were used for analysis of change over time. To validate new questions on intrusive thoughts, written answers to open-ended questions were read and analyzed by qualitative content analysis. RESULTS: Before surgery, 603 men (73%) reported negative intrusive thoughts about their cancer at some time in the past month and 593 men (59%) reported such thoughts three months after surgery. Comparing those reporting intrusive thoughts at least weekly or once a week before surgery with those who did not, the prevalence ratio (95% confidence interval), three months after surgery, for waking up in the middle of the night with anxiety was 3.9 (2.7 to 5.5), for depressed mood 1.8 (1.6 to 2.1) and for impaired self-assessed quality of life 1.3 (1.2 to 1.5). CONCLUSION: The prevalence of negative intrusive thoughts about prostate cancer at the time of surgery associates with studied quality-of-life outcomes three months later. TRIAL REGISTRATION: Current Controlled Trials, ISRCTN06393679.

Effects on Serum Hormone Concentrations after a Dietary Phytoestrogen Intervention in Patients with Prostate Cancer: A Randomized Controlled Trial.

Phytoestrogens have been suggested to have an anti-proliferative role in prostate cancer, potentially by acting through estrogen receptor beta (ERß) and modulating several hormones. We primarily aimed to investigate the effect of a phytoestrogen intervention on hormone concentrations in blood depending on the ERß genotype. Patients with low and intermediate-risk prostate cancer, scheduled for radical prostatectomy, were randomized to an intervention group provided with soybeans and flaxseeds (∼200 mg phytoestrogens/d) added to their diet until their surgery, or a control group that was not provided with any food items. Both groups received official dietary recommendations. Blood samples were collected at baseline and endpoint and blood concentrations of different hormones and phytoestrogens were analyzed. The phytoestrogen-rich diet did not affect serum concentrations of testosterone, insulin-like growth factor 1, or sex hormone-binding globulin (SHBG). However, we found a trend of decreased risk of increased serum concentration of estradiol in the intervention group compared to the control group but only in a specific genotype of ERß (p = 0.058). In conclusion, a high daily intake of phytoestrogen-rich foods has no major effect on hormone concentrations but may lower the concentration of estradiol in patients with prostate cancer with a specific genetic upset of ERß.

The effect of a phytoestrogen intervention and impact of genetic factors on tumor proliferation markers among Swedish patients with prostate cancer: study protocol for the randomized controlled PRODICA trial.

BACKGROUND: A high intake of phytoestrogens, found in soy, rye, and seeds, is associated with a reduced risk of a prostate cancer diagnosis. Previously, we found that the overall decreased risk of prostate cancer diagnosis in males with a high intake of phytoestrogens was strongly modified by a nucleotide sequence variant in the estrogen receptor-beta (ERß) gene. However, we do not know if phytoestrogens can inhibit the growth of prostate cancer in males with established diseases. If there is an inhibition or a delay, there is reason to believe that different variants of the ERß gene will modify the effect. Therefore, we designed an intervention study to investigate the effect of the addition of foods high in phytoestrogens and their interaction with the ERß genotype on prostate tumor proliferation in patients with prostate cancer. METHOD: The PRODICA trial is a randomized ongoing intervention study in patients with low- and intermediate-risk prostate cancer with a Gleason score < 8, prostate-specific antigen (PSA) < 20, and scheduled for radical prostatectomy. The study is conducted at Sahlgrenska University Hospital in Gothenburg, Sweden. The intervention consists of a daily intake of soybeans and flaxseeds (~ 200 mg of phytoestrogens) until the surgery, approximately 6 weeks. The aim is to recruit 200 participants. The primary outcome is the difference in the proliferation marker Ki-67 between the intervention and the control groups. The genotype of ERß will be investigated as an effect-modifying factor. Secondary outcomes include, e.g., concentrations of PSA and steroid hormones in the blood. DISCUSSION: The results of the PRODICA trial will contribute important information on the relevance of increasing the intake of phytoestrogens in patients with prostate cancer who want to make dietary changes to improve the prognosis of their cancer. If genetic factors turn out to influence the effect of the intervention diet, dietary advice can be given to patients who most likely benefit from it. Dietary interventions are cost-effective, non-invasive, and result in few mild side effects. Lastly, the project will provide basic pathophysiological insights which could be relevant to the development of treatment strategies for patients with prostate cancer. CLINICALTRIALS: gov NCT02759380. Registered on 3 May 2016.

Development and Validation of a Mobile Phone Application Developed for Measuring Dietary Fiber Intake.

We have developed a mobile phone application for measuring the intake of dietary fiber and validated the ability of the application to accurately capture this intake against measurements registered by a dietary record. We also investigated what food groups contributed most to the total, soluble, and insoluble dietary fiber intake. Twenty-six randomly selected Swedish women aged 35-85 years were included and randomized to either start to register dietary intake in the application or by a dietary record, during three consecutive days. After a washout period of at least two weeks, the participants used the other method. We found that the difference in measured mean fiber intake between the dietary record and the application was two grams independent of the total intake per day. A statistically significant correlation between fiber intake as measured by the two methods was found (rho = 0.65, p < 0.001). Vegetables and roots were the predominantly contributing foods to total and soluble fiber intake. Bread and crackers contributed most to insoluble fiber intake. In conclusion, the application may be considered as a useful and easy-to-use method to measure dietary fiber intake.

A Preparatory Study for a Randomized Controlled Trial of Dietary Fiber Intake During Adult Pelvic Radiotherapy.

Background: Patients undergoing pelvic radiotherapy are often advised to omit fiber-rich foods from their diet to reduce the adverse effects of treatment. Scientific evidence supporting this recommendation is lacking, and recent studies on animals and humans have suggested that there is a beneficial effect of dietary fiber for the alleviation of symptoms. Randomized controlled studies on dietary fiber intake during pelvic radiotherapy of sufficient size and duration are needed. As preparation for such a large-scale study, we evaluated the feasibility, compliance, participation rate, and logistics and report our findings here in this preparatory study. Methods: In this preparatory study of a fiber intervention trial, Swedish gynecological cancer patients scheduled for radiotherapy were recruited between January 2019 and August 2020. During the intervention, the participants filled out questionnaires and used an application. They also consumed a fiber supplement at first in powder form, later in capsules. Blood- and fecal samples were collected. The study is registered in clinicaltrials.gov (https://clinicaltrials.gov/ct2/show/NCT04534075?cond=fidura&draw=2&rank=1). Results: Among 136 approached patients, 57 started the study and the participation rate for primary outcomes was 63% (third blood sample) and 65% (third questionnaire). Barely half of the participants provided fecal samples. Providing concise and relevant information to the patients at the right time was crucial in getting them to participate and stay in the study. The most common reasons for declining participation or dropping out were the expected burden of radiotherapy or acute side effects. Tailoring the ambition level to each patient concerning the collection of data beyond the primary endpoints was an important strategy to keep the dropout rate at an acceptable level. Using capsules rather than psyllium in powder form made it much easier to document intake and to create a control group. During the course of the preparatory study, we improved the logistics and for the last 12 participants included, the participation rate was 100% for the earliest primary outcome. Conclusion: A variety of adjustments in this preparatory study resulted in an improved participation rate, which allowed us to set a final protocol and proceed with the main study.

Dietary intake of fish, omega-3, omega-6 polyunsaturated fatty acids and vitamin D and the prevalence of psychotic-like symptoms in a cohort of 33,000 women from the general population.

BACKGROUND: Low intake of fish, polyunsaturated fatty acids (PUFA) and vitamin D deficiency has been suggested to play a role in the development of schizophrenia. Our aim was to evaluate the association between the intake of different fish species, PUFA and vitamin D and the prevalence of psychotic-like symptoms in a population-based study among Swedish women. METHODS: Dietary intake was estimated using a food frequency questionnaire among 33,623 women aged 30-49 years at enrollment (1991/92). Information on psychotic-like symptoms was derived from a follow-up questionnaire in the years 2002/03. Participants were classified into three predefined levels: low, middle and high frequency of symptoms. The association between diet and psychotic-like symptoms was summarized in terms of relative risks (RR) and corresponding 95% confidence intervals and was evaluated by energy-adjusted multinomial logistic regression. RESULTS: 18,411 women were classified as having a low level of psychotic-like symptoms, 14 395 as middle and 817 as having a high level. The risk of high level symptoms was 53% (95% CI, 30-69%) lower among women who ate fish 3-4 times per week compared to women who never ate fish. The risk was also lower for women with a high intake of omega-3 and omega-6 PUFA compared to women with a lower intake of these fatty acids. The effect was most pronounced for omega-6 PUFAs. The RR comparing the highest to the lowest quartile of omega-6 PUFAs intake was 0.78 (95% CI, 0.64-0.97). The associations were J-shaped with the strongest reduced risk for an intermediate intake of fish or PUFA. For fatty fish (herring/mackerel, salmon-type fish), the strongest inverse association was found for an intermediate intake (RR: 0.81, 95% CI, 0.66-0.98), whereas a high intake of fatty fish was associated with an increased risk of psychotic-like symptoms (RR: 1.90, 95% CI, 1.34-2.70). Women in the highest compared with the lowest quartile of vitamin D consumption experienced a 37% (95% CI, 22-50%) lower risk of psychotic-like symptoms. CONCLUSION: Our findings raise a possibility that adult women with a high intake of fish, omega-3 or omega-6 PUFA and vitamin D have a lower rate of psychotic-like symptoms.

Intake of citrus fruits and vegetables and the intensity of defecation urgency syndrome among gynecological cancer survivors.

BACKGROUND: Despite the experimental evidence that certain dietary compounds lower the risk of radiation-induced damage to the intestine, clinical data are missing and dietary advice to irradiated patients is not evidence-based. MATERIALS AND METHODS: We have previously identified 28 intestinal health-related symptoms among 623 gynaecological-cancer survivors (three to fifteen years after radiotherapy) and 344 matched population-based controls. The 28 symptoms were grouped into five radiation-induced survivorship syndromes: defecation-urgency syndrome, fecal-leakage syndrome, excessive mucus discharge, excessive gas discharge and blood discharge. The grouping was based on factor scores produced by Exploratory Factor Analysis in combination with the Variable Cutoff Method. Frequency of food intake was measured by a questionnaire. We evaluated the relationship between dietary intake and the intensity of the five syndromes. RESULTS: With the exception of excessive mucus discharge, the intensity of all syndromes declined with increasing intake of citrus fruits. The intensity of defecation-urgency and fecal-leakage syndrome declined with combined intake of vegetables and citrus fruits. The intensity of excessive mucus discharge was increased with increasing intake of gluten. CONCLUSION: In this observational study, we found an association between a high intake of citrus fruits and vegetables and a lower intensity of the studied radiation-induced cancer survivorship syndromes. Our data suggest it may be worthwhile to continue to search for a role of the diet before, during and after radiotherapy to help the cancer survivor restore her or his intestinal health after irradiation.

Dietary phytoestrogens are not associated with risk of overall breast cancer but diets rich in coumestrol are inversely associated with risk of estrogen receptor and progesterone receptor negative breast tumors in Swedish women.

Results from epidemiological and experimental studies indicate that phytoestrogens may protect against breast cancer. Because one of the biological effects of phytoestrogens is probably estrogenic, it's possible that the preventive effect on breast cancer differs by estrogen receptor (ER) or progesterone receptor (PR) status of the tumor. We evaluated the associations between dietary phytoestrogen (isoflavonoids, lignans, and coumestrol) intake and risk of breast cancer and whether the ER/PR statuses of the tumor influence this relationship. In 1991-2 a prospective population-based cohort study among Swedish pre- and postmenopausal women was performed, making questionnaire data available for 45,448 women. A total of 1014 invasive breast cancers were diagnosed until December 2004. Cox proportional hazards models were performed to estimate multivariate risk ratios, 95% CI for associations with risk of breast cancer. Intakes of lignan, isoflavonoid, or coumestrol were not associated with breast cancer risk overall or before or after 50 y of age. The effects of lignans or isoflavonoids were independent of receptor status. However, intake of coumestrol was associated with decreased risk of receptor negative tumors (ER-PR-) but not positive tumors. The risk of ER-PR- tumors was significantly lower (50%) in women with intermediate coumestrol intake compared with those who did not consume any. In conclusion, we found no association between intake of isoflavonoids or lignans and breast cancer risk. Our results of a decreased risk of ER-PR- tumors in women with intermediate intake of coumestrol could be due to chance because of the low intake. The results should be confirmed in other studies.

[Differing dietary advice are given to gynaecological and prostate cancer patients receiving radiotherapy in Sweden]. / Stor variation i kostråden vid strålbehandling av lilla bäckenet - Kost har potential att förebygga följdsjukdomar till strålning och ge bättre tarmhälsa ­ men vetenskaplig evidens saknas.

Preclinical studies indicate that an optimal diet during pelvic radiotherapy may be able to prevent radiation-induced survivorship diseases that diminish cancer survivors' intestinal health. We do not yet know what this optimal diet might be because scientific studies needed to determine what dietary advice might best be given to patients during treatment. Oncology clinics in Sweden were contacted to determine the nature of dietary advice given to gynaecological and prostate cancer patients at each clinic before, during and after radiotherapy. Reports from these clinics revealed that dietary advice given to patients differs from one clinic to another. This was as expected, since it was known that the scientific evidence needed to identify the best possible diet is not yet available. Clinical studies of the effects of different diets are urgently needed if we are to prevent survivorship diseases that decrease intestinal health.

Lactase persistence, dietary intake of milk, and the risk for prostate cancer in Sweden and Finland.

Prostate carcinoma is the most common cancer in men. Its primary pathogenesis is mostly unknown. Dairy products containing lactose have been suggested to be risk factors for prostate cancer. Digestion of lactose is dependent on lactase activity in the intestinal wall. A single nucleotide polymorphism C to T residing 13,910 bp upstream of the lactase gene has been shown to associate with the developmental down-regulation of lactase activity underlying persistence/nonpersistence trait. To find out whether lactase persistence is related to the risk for prostate cancer, we genotyped 1,229 Finnish and 2,924 Swedish patients and their 473 Finnish and 1,842 Swedish controls using solid-phase minisequencing. To explore if dairy products have an association with prostate cancer, we analyzed the milk consumption in the Swedish study consisting of 1,499 prostate cancer patients and 1,130 controls (Cancer Prostate in Sweden I study) using a questionnaire. Only the consumption of low-fat milk was found to be associated with increased risk of prostate cancer [odds ratio (OR), 1.73; 95% confidence interval (95% CI), 1.16-2.39]. A statistically significantly higher (P < 0.01) lactose intake was observed among subjects with high lactase activity (C/T and T/T genotypes) compared with those with low lactase activity (C/C genotype). Lactase persistence did not associate with increased risk for prostate carcinoma in the Finnish (OR, 1.11; 95% CI, 0.83-1.47; P = 0.488) or in the Swedish populations (OR, 1.16; 95% CI, 0.91-1.46; P = 0.23). In conclusion, lactase persistence/nonpersistence contains no risk for prostate cancer. Analysis of different milk products showed some evidence for low-fat milk as a potential risk factor for prostate cancer.

Sequence variants of toll-like receptor 4 are associated with prostate cancer risk: results from the CAncer Prostate in Sweden Study.

Inflammation has been implicated as an etiological factor in several human cancers. Growing evidence suggests that chronic inflammation may also play a role in the etiology of prostate cancer. Considering that genetic susceptibility is a major risk factor for this disease, we hypothesize that sequence variants in genes that regulate inflammation may modify individual susceptibility to prostate cancer. The lipopolysaccharide receptor Toll-like receptor 4 (TLR4) is a central player in the signaling pathways of the innate immune response to infection by Gram-negative bacteria and is an important candidate inflammatory gene. We performed a systematic genetic analysis of TLR4 sequence variants by evaluating eight single-nucleotide polymorphisms that span the entire gene among 1383 newly diagnosed prostate cancer patients and 780 age- and residence-matched controls in Sweden. We found an association between a sequence variant (11381G/C) in the 3'-untranslated region of the TLR4 gene and prostate cancer risk. The frequency of the variant genotypes (CG or CC) was significantly higher in the patients (24.1%) than in the controls (19.7%; P = 0.02). The frequency of risk genotypes among patients diagnosed before the age of 65 years was even higher (26.3%). Compared with men who had the wild-type genotype of this single-nucleotide polymorphism (GG), those with GC or CC genotypes had a 26% increased risk for prostate cancer (odds ratio, 1.26; 95% confidence interval, 1.01-1.57) and 39% increased risk increased risk for early onset prostate cancer (before age 65 years; odds ratio, 1.39; 95% confidence interval, 1.02-1.91). The risk attributable to this variant for prostate cancer in Sweden was estimated to be 4.9%. Although the biological mechanism of the observed association remains to be elucidated, our finding supports a role for a bacteria-associated response pathway, possibly acting via inflammation, in the development of prostate cancer.

Validity of a web-based dietary questionnaire designed especially to measure the intake of phyto-oestrogens.

A diet questionnaire (DQ) designed to assess habitual diet and phyto-oestrogen intake was developed. This study aimed to examine the validity of the DQ in men, with and without having prostate cancer. The DQ was validated against alkylresorcinol metabolites measured in urine as objective biomarkers of whole grain wheat and rye (WG) intake, and a 4-d estimated food record (FR) was used for relative comparison. Participants (n 61) completed both methods and provided spot urine samples. We found a statistically significant correlation between the DQ and FR for reported whole grain intake and isoflavonoids, as well as for intake of macronutrients, except protein. The correlation coefficient between the two methods was on average r 0·30, lowest for lignans (r -0·11) and highest for alcohol (r 0·65). Reported energy intake was lower in the DQ compared with FR (8523 v. 9249 kJ (2037 v. 2211 kcal), respectively; P = 0·014). Bland-Altman plots showed an acceptable agreement; most cases were within the limits (95 % CI) of agreement on reported energy intake, as well as intake of macronutrients, except protein (which was underestimated in the DQ compared with the FR). The correlation of alkylresorcinol with WG intake was statistically significant in the DQ (r 0·31, P = 0·015), but not in the FR (r 0·18, P = 0·12) and the weighted κ was 0·29 and 0·11, respectively. In conclusion, the results showed that the DQ have a reasonable validity for measuring WG intake and most nutrients, and, after some adjustments regarding protein intake assessment have been made, the DQ will be a promising tool.

Mean absorbed dose to the anal-sphincter region and fecal leakage among irradiated prostate cancer survivors.

PURPOSE: To supplement previous findings that the absorbed dose of ionizing radiation to the anal sphincter or lower rectum affects the occurrence of fecal leakage among irradiated prostate-cancer survivors. We also wanted to determine whether anatomically defining the anal-sphincter region as the organ at risk could increase the degree of evidence underlying clinical guidelines for restriction doses to eliminate this excess risk. METHODS AND MATERIALS: We identified 985 men irradiated for prostate cancer between 1993 and 2006. In 2008, we assessed long-term gastrointestinal symptoms among these men using a study-specific questionnaire. We restrict the analysis to the 414 men who had been treated with external beam radiation therapy only (no brachytherapy) to a total dose of 70 Gy in 2-Gy daily fractions to the prostate or postoperative prostatic region. On reconstructed original radiation therapy dose plans, we delineated the anal-sphincter region as an organ at risk. RESULTS: We found that the prevalence of long-term fecal leakage at least once per month was strongly correlated with the mean dose to the anal-sphincter region. Examining different dose intervals, we found a large increase at 40 Gy; ≥ 40 Gy compared with <40 Gy gave a prevalence ratio of 3.8 (95% confidence interval 1.6-8.6). CONCLUSIONS: This long-term study shows that mean absorbed dose to the anal-sphincter region is associated with the occurrence of long-term fecal leakage among irradiated prostate-cancer survivors; delineating the anal-sphincter region separately from the rectum and applying a restriction of a mean dose <40 Gy will, according to our data, reduce the risk considerably.

Dietary phytoestrogens and the risk of ovarian cancer in the women's lifestyle and health cohort study.

BACKGROUND: Dietary intake of phytoestrogens has been inversely associated to hormone-dependent cancers, such as prostate and breast cancers. Few studies have investigated the association between ovarian cancer and intake of phytoestrogens. We evaluated the associations between intake of phytoestrogens (isoflavonoids/lignans/coumestrol) and fiber (vegetable/cereal) and risk of ovarian cancer. METHODS: In 1991-1992 a prospective population-based cohort study among Swedish women was conducted, including 47,140 women with complete dietary questionnaire data. During follow-up until December 2007, 163 women developed invasive (n = 117) and borderline (n = 46) ovarian cancers. The median follow-up time was 16 years and total person year was 747,178. Cox proportional hazards models were conducted to estimate multivariate risk ratios, 95% CI for associations with risk of ovarian cancer. RESULTS: We found no association between intake of phytoestrogens or fiber and overall ovarian cancer risk. In addition, we found no statistically significant association between intake of specific food items rich in phytoestrogens (berries, nuts, beans/soy, and crisp or whole-grain bread) and ovarian cancer risk overall. Fiber and coumestrol was inversely associated with borderline ovarian cancer, but not with invasive ovarian cancer. CONCLUSIONS: We found no association between intake of phytoestrogens or fiber and overall ovarian cancer risk. IMPACT: Phytoestrogens do not play a major etiologic role in ovarian cancer, at least among women in this Swedish cohort with low bean/soy intake. However, our results of a difference in the effect of fiber or coumestrol between invasive and borderline ovarian cancer need to be evaluated in larger studies.

Tobacco smoking and long-lasting symptoms from the bowel and the anal-sphincter region after radiotherapy for prostate cancer.

BACKGROUND AND PURPOSE: Tobacco smoking can cause vascular injury, tissue hypoxia and fibrosis as can ionizing radiation. However, we do not know if tobacco smoking increases the risk of long-term side effects after radiotherapy for prostate cancer. METHODS: We identified 985 men treated with radiotherapy for prostate cancer between 1993 and 2006. In 2008, long-lasting symptoms appearing after radiotherapy for prostate cancer were assessed through a study-specific questionnaire as were smoking habits and demographic factors of all these men. In the questionnaire the prostate-cancer survivors were asked to report symptom occurrence the previous six months. RESULTS: We obtained information on tobacco smoking from 836 of the 985 prostate-cancer survivors with a median time to follow-up of six years (range 2-14 years). The prevalence ratio of defecation urgency among current smokers compared to never smokers was 1.6 (95% CI 1.2-2.2). Corresponding prevalence ratio for diarrhea was 2.8 (95% CI 1.2-6.5), the sensation of bowel not completely emptied after defecation 2.1 (95% CI 1.3-3.3) and for sudden emptying of all stools into clothing without forewarning 4.7 (95% CI 2.3-9.7). CONCLUSION: Tobacco smoking among prostate-cancer survivors treated with radiotherapy increases the risk of certain long-lasting symptoms from the bowel and anal-sphincter region.

Association of frequent consumption of fatty fish with prostate cancer risk is modified by COX-2 polymorphism.

Dietary intake of marine fatty acids from fish may protect against prostate cancer development. We studied this association and whether it is modified by genetic variation in cyclooxygenase (COX)-2, a key enzyme in fatty acid metabolism and inflammation. We assessed dietary intake of fish among 1,499 incident prostate cancer cases and 1,130 population controls in Sweden. Five single nucleotide polymorphisms (SNPs) were identified and genotyped in available blood samples for 1,378 cases and 782 controls. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by multivariate logistic regression. Multiplicative and additive interactions between fish intake and COX-2 SNPs on prostate cancer risk were evaluated. Eating fatty fish (e.g., salmon-type fish) once or more per week, compared to never, was associated with reduced risk of prostate cancer (OR: 0.57, 95% CI: 0.43-0.76). The OR comparing the highest to the lowest quartile of marine fatty acids intake was 0.70 (95% CI: 0.51-0.97). We found a significant interaction (p < 0.001) between salmon-type fish intake and a SNP in the COX-2 gene (rs5275: +6365 T/C), but not with the 4 other SNPs examined. We found strong inverse associations with increasing intake of salmon-type fish among carriers of the variant allele (OR for once per week or more vs. never = 0.28, 95% CI: 0.18-0.45; p(trend) < 0.01), but no association among carriers of the more common allele. Frequent consumption of fatty fish and marine fatty acids appears to reduce the risk of prostate cancer, and this association is modified by genetic variation in the COX-2 gene.

Dietary intake of phytoestrogens, estrogen receptor-beta polymorphisms and the risk of prostate cancer.

BACKGROUND: The causes of prostate cancer are poorly understood, but genetic factors may be more important than for many other malignancies, and dietary phytoestrogens may be protective. Because phytoestrogens bind tightly to the estrogen receptor-beta, we conducted an epidemiologic investigation of synergistic effects between phytoestrogen intake and estrogen receptor-beta gene polymorphisms. METHODS: We performed a population-based case-control study in Sweden. All participants reported their phytoestrogen intake and donated a blood sample. We identified four haplotype-tagging single nucleotide polymorphisms (htSNPs) and genotyped these htSNPs in 1314 prostate cancer patients and 782 controls. Odds ratios were estimated by multivariate logistic regression. Interactions between phytoestrogen intake and estrogen receptor-beta SNPs on prostate cancer risk were evaluated considering both multiplicative and additive effect scales. RESULTS: We found a significant multiplicative interaction (P = 0.04) between dietary intake of phytoestrogens and a promoter SNP in the estrogen receptor-beta gene (rs 2987983-13950), but not with any of the three other htSNPs (P = 0.11, 0.69, 0.85). Among carriers of the variant promoter alleles, we found strong inverse associations with increasing intake of total phytoestrogens (odds ratio for highest vs. lowest quartile = 0.43; P for trend <0.001), isoflavonoids (odds ratio = 0.63; P for trend = 0.05), and coumestrol (odds ratio = 0.57; P for trend = 0.003). We found no association between phytoestrogens and prostate cancer among carriers homozygous for the wild-type allele (TT). CONCLUSIONS: Our study provides strong evidence that high intake of phytoestrogens substantially reduce prostate cancer risk among men with specific polymorphic variation in the promoter region of the estrogen receptor-beta gene.