Lack of prospective associations between plasma and urinary phytoestrogens and risk of prostate or colorectal cancer in the European Prospective into Cancer-Norfolk study

Dietary phytoestrogens are suggested to reduce the risk of prostate and colorectal cancer, but the results of epidemiologic studies have not yielded consistent support for this proposed effect, possibly due to inadequate databases of phytoestrogen levels in foods. Biomarkers of phytoestrogen intakes may provide a clearer insight into the relationship between phytoestrogen exposure and the risk of prostate or colorectal cancer risks. From the European Prospective into Cancer-Norfolk cohort (ages 45-75), serum and urine samples were analyzed for seven phytoestrogens [daidzein, enterodiol, enterolactone, genistein, glycitein, O-desmethylangolensin (O-DMA), and equol] among 193 cases of prostate cancer and 828 controls, and 221 cases of colorectal cancer with 889 controls. Summary variables of total lignans (enterodiol and enterolactone) and total isoflavones (daidzein, genistein, O-DMA, equol, and glycitein) were created and analyzed in conjunction with individual phytoestrogens. Logistic regression analyses revealed that there was no significant association between prostate cancer risk and total serum isoflavones [odds ratio (OR), 1.01; 95% confidence interval (CI), 0.93-1.10] or total serum lignans (OR, 0.94; 95% CI, 0.86-1.04) or between colorectal cancer risk and total serum isoflavones (OR, 1.01; 95% CI, 0.94-1.08) or total serum lignans (OR, 1.03; 95% CI, 0.94-1.12). Similarly, null associations were observed for individual serum phytoestrogens and for all urinary phytoestrogen biomarkers. In conclusion, we have found no evidence to support an inverse association between phytoestrogen exposure and prostate or colorectal cancer risk.     

Urinary phytoestrogen excretion and prostate cancer risk: a nested case�Ccontrol study in the Multiethnic Cohort

Background:

Phytoestrogens are of special interest in prostate cancer research because populations in Asia with a high consumption of phytoestrogens have a lower incidence of the disease than comparable populations in Western countries.

Methods:

This case–control study is nested within a large multiethnic cohort in Hawaii and California. Urine samples were analysed for daidzein, genistein, equol, and enterolactone among 249 incident prostate cancer cases and 404 controls matched on age, race/ethnicity, date/time of specimen collection, and fasting status.

Results:

The median excretion of daidzein was 0.173 nmol mg⁻¹ creatinine in cases and 0.291 in controls (P=0.01), and the median excretion of genistein was 0.048 in cases and 0.078 in controls (P=0.05). An inverse association was seen for daidzein overall (odds ratio for the highest vs lowest quintile=0.55, 95% confidence interval=0.31–0.98, P_trend=0.03) and seemed to apply to localized (P_trend=0.08) as well as advanced or high-grade cancer (P_trend=0.09). This association was consistent across the four ethnic groups examined. Although the relationship was weaker for genistein, the odds ratios and trends were similarly inverse. Urinary excretion of equol and enterolactone was not significantly related to prostate cancer risk.

Conclusion:

Our findings suggest that high intake of isoflavones, as reflected by urinary excretion of daidzein and genistein, may be protective against prostate cancer.     

Lignans and breast cancer risk in pre- and post-menopausal women: meta-analyses of observational studies

Phyto-oestrogens are plant compounds structurally similar to oestradiol, which have been proposed to have protective effects against breast cancer. The main class of phyto-oestrogens in the Western diet is lignans. Literature reports on the effect of lignans in breast cancer risk have been conflicting. We performed three separate meta-analyses to examine the relationships between (i) plant lignan intake, (ii) enterolignan exposure and (iii) blood enterolactone levels and breast cancer risk. Medline, BIOSIS and EMBASE databases were searched for publications up to 30 September 2008, and 23 studies were included in the random effects meta-analyses. Overall, there was little association between high plant lignan intake and breast cancer risk (11 studies, combined odds ratio (OR): 0.93, 95% confidence interval (95% CI): 0.83–1.03, P=0.15), but this association was subjected to marked heterogeneity (I²=44%). Restricting the analysis to post-menopausal women, high levels of plant lignan intake were associated with reduced breast cancer risk (7 studies, combined OR: 0.85, 95% CI: 0.78, 0.93, P<0.001) and heterogeneity was markedly reduced (I²=0%). High enterolignan exposure was also associated with breast cancer (5 studies, combined OR: 0.73, 95% CI: 0.57, 0.92, P=0.009) but, again, there was marked heterogeneity (I²=63%). No association was found with blood enterolactone levels (combined OR: 0.82, 95% CI: 0.59–1.14, P=0.24). In conclusion, plant lignans may be associated with a small reduction in post-menopausal breast cancer risk, but further studies are required to confirm these results.     

Urinary phytoestrogens and risk of prostate cancer in Jamaican men

We evaluated the relationship of spot urinary concentrations of phytoestrogens with total prostate cancer and tumor grade in a hospital-based case–control study in Jamaica. Urine samples were analyzed for genistein, daidzein, equol (isoflavones), and enterolactone (lignan) among newly diagnosed cases (n = 175) and controls (n = 194). Urinary concentrations of enterolactone (lignan) were higher among cases. There were no significant differences in median concentrations of isoflavone excretion. Compared with non-producers of equol (reference tertile), men who produced equol were at decreased risk of total prostate cancer (tertile 2: OR, 0.42; CI, 0.23–0.75) (tertile 3: OR, 0.48; CI, 0.26–0.87) (p _trend, 0.020) and high-grade disease (tertile 2: OR, 0.31; CI, 0.15–0.61) (tertile 3: OR, 0.29; CI, 0.13–0.60) (p _trend, 0.001). Higher concentrations of enterolactone were positively related to total prostate cancer (OR, 1.85; CI, 1.01–3.44; p _trend, 0.027) as well as high-grade disease (OR, 2.46; CI, 1.11–5.46; p _trend, 0.023). There were no associations between urinary excretion of genistein and daidzein with risk of prostate cancer. Producers of equol (isoflavone) may be at reduced risk of total- and high-grade prostate cancer whereas enterolactone may increase the likelihood of disease.     

Phytoestrogen concentrations in serum and spot urine as biomarkers for dietary phytoestrogen intake and their relation to breast cancer risk in European prospective investigation of cancer and nutrition-norfolk.

Subjects of this study consisted of 333 women (aged 45-75 years) drawn from a large United Kingdom prospective study of diet and cancer, the European Prospective Investigation of Cancer and Nutrition-Norfolk study. Using newly developed gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry methods incorporating triply (13)C-labeled standards, seven phytoestrogens (daidzein, genistein, glycitein, O-desmethylangolensin, equol, enterodiol, and enterolactone) were measured in 114 spot urines and 97 available serum samples from women who later developed breast cancer. Results were compared with those from 219 urines and 187 serum samples from healthy controls matched by age and date of recruitment. Dietary levels were low, but even so, mean serum levels of phytoestrogens were up to 600 times greater than postmenopausal estradiol levels. Phytoestrogen concentrations in spot urine (adjusted for urinary creatinine) correlated strongly with that in serum, with Pearson correlation coefficients > 0.8. There were significant relationships (P < 0.02) between both urinary and serum concentrations of isoflavones across increasing tertiles of dietary intakes. Urinary enterodiol and enterolactone and serum enterolactone were significantly correlated with dietary fiber intake (r = 0.13-0.29). Exposure to all isoflavones was associated with increased breast cancer risk, significantly so for equol and daidzein. For a doubling of levels, odds ratios increased by 20-45% [log(2) odds ratio = 1.34 (1.06-1.70; P = 0.013) for urine equol, 1.46 (1.05-2.02; P = 0.024) for serum equol, and 1.22 (1.01-1.48; P = 0.044) for serum daidzein]. These estimates of risk are similar to those established for estrogens and androgens in postmenopausal breast cancer but need confirmation in larger studies.     

Dietary phytoestrogen intake and premenopausal breast cancer risk in a German case-control study

A diet high in isoflavonoids (soy) is associated with lower breast cancer risk in Asian populations. Due to the low soy intake, dietary lignans may be the more important phytoestrogen class in Western populations. We used a population-based case-control study of breast cancer by age 50 in southern Germany to evaluate the association between dietary intake of different phytoestrogens and premenopausal breast cancer risk. Dietary information was collected from 278 premenopausal cases and 666 age-matched controls, using a validated FFQ. Using multivariate logistic regression, the highest vs. lowest intake quartiles of daidzein and genistein yielded significantly reduced ORs (95% CI) for breast cancer risk of 0.62 (0.40-0.95) and 0.47 (0.29-0.74), respectively. The protective effects of daidzein and genistein were found only for hormone receptor-positive tumors. High intake of other isoflavonoids, e.g., formononetin and biochanin A, as well as the sum of isoflavonoids were not associated with a decrease in risk. Breast cancer risk significantly decreased with a high intake of the plant lignan matairesinol (OR = 0.58, 95% CI 0.37-0.94) but not secoisolariciresinol or the sum of plant lignans. However, both estimated mammalian lignans, enterodiol and enterolactone, were inversely associated with breast cancer risk, with ORs (95% CI) of 0.61 (0.39-0.98) and 0.57 (0.35-0.92), respectively. No effect was found for total phytoestrogen intake. Our results suggest an important role of dietary intake of daidzein and genistein, despite low levels, as well as of matairesinol and mammalian lignans to reduce premenopausal breast cancer risk in this study population.     

Phytoestrogen exposure is associated with circulating sex hormone levels in postmenopausal women and interact with ESR1 and NR1I2 gene variants.

In this large cross-sectional study, we investigated the relationship between phytoestrogen exposure and circulating sex hormones and sex hormone-binding globulin (SHBG) levels in 1988 healthy postmenopausal women and their interactions with polymorphisms in genes involved in estrogen signaling. Plasma estradiol, testosterone, androstenedione, estrone, and SHBG were measured. Urinary levels of five isoflavones (daidzein, genistein, glycitein, O-desmethylangolensin, and equol) and two lignans (enterodiol and enterolactone) were measured and used as biomarkers for dietary intakes. Eighteen polymorphisms in ESR1, ESR2, and NR1I2 genes were genotyped. Results showed that lignans were positively associated with plasma SHBG levels (eta(p)(2) = 1.2%; P < 0.001) and negatively associated with plasma testosterone (eta(p)(2) = 0.2%; P = 0.042). Equol was negatively associated with plasma estradiol levels (eta(p)(2) = 0.3%; P = 0.028), whereas O-desmethylangolensin was positively associated with plasma estradiol level (eta(p)(2) = 0.3%; P = 0.010). There were significant phytoestrogen interactions with polymorphisms in ESR1 and NR1I2 genes in affecting estrone levels. We conclude that phytoestrogens modulate sex hormone and SHBG levels in postmenopausal women and interact with gene variants involved in estrogen signaling. Such phytoestrogen-gene interactions may explain the conflicting literature on the hormonal effects of phytoestrogens.     

Stimulation of breast cancer cellsin vitro by the environmental estrogen enterolactone and the phytoestrogen equol

Summary The phenolic lignans enterolactone and enterodiol appear periodically in women's urine, dependent upon synthesis from plant-derived lignans by the intestinal microflora. The phytoestrogen equol is also present in women's urine, and is also derived from a vegetarian diet. Antiestrogenic or antiproliferative actions of these compounds have been postulated and related to the observation that there is a reduced incidence of breast cancer associated with diet. We evaluated the estrogenic and antiestrogenic activity of these compounds using four sensitive assays in tissue culture, including the use of human breast cancer cell lines T47D and MCF-7. Unexpectedly, we found that enterolactone and enterodiol, as well as equol, are weak estrogens, and that enterolactone and equol could stimulate the growth of estrogen-dependent breast cancer cell lines. We suggest that these environmental agents can promote the growth of breast cancer, particularly hormone-dependent metastases that may be located near the gut or in the mesenteries or liver, where the concentration of these intestinally produced compounds would be highest. Treatment with an antiestrogen such as tamoxifen blocks the estrogenic activity of these compounds. In the absence of treatment with an antiestrogen such as tamoxifen, hormonal therapy to block steroidal estrogen synthesis in a patient with breast cancer could conceivably be circumvented by a vegeterian diet rich in the precursors to estrogenic compounds such as enterolactone and equol.     

Dietary cadmium exposure and prostate cancer incidence: a population-based prospective cohort study

Background:

Experimental data convincingly propose the toxic metal cadmium as a prostate carcinogen. Cadmium is widely dispersed into the environment and, consequently, food is contaminated.

Methods:

A population-based cohort of 41 089 Swedish men aged 45–79 years was followed prospectively from 1998 through 2009 to assess the association between food frequency questionnaire-based estimates of dietary cadmium exposure (at baseline, 1998) and incidence of prostate cancer (3085 cases, of which 894 were localised and 794 advanced) and through 2008 for prostate cancer mortality (326 fatal cases).

Results:

Mean dietary cadmium exposure was 19 μg per day±s.d. 3.7. Multivariable-adjusted dietary cadmium exposure was positively associated with overall prostate cancer, comparing extreme tertiles; rate ratio (RR) 1.13 (95% confidence interval (CI): 1.03–1.24). For subtypes of prostate cancer, the RR was 1.29 (95% CI: 1.08–1.53) for localised, 1.05 (95% CI: 0.87–1.25) for advanced, and 1.14 (95% CI: 0.86–1.51) for fatal cases. No statistically significant difference was observed in the multivariable-adjusted risk estimates between tumour subtypes (P_{heterogeneity}=0.27). For localised prostate cancer, RR was 1.55 (1.16–2.08) among men with a small waist circumference and RR 1.45 (1.15, 1.83) among ever smokers.

Conclusion:

Our findings provide support that dietary cadmium exposure may have a role in prostate cancer development.     

Height and risk of prostate cancer in the prostate, lung, colorectal, and ovarian cancer screening trial

Background:

The relationship between prostate cancer and height is uncertain.

Methods:

We prospectively examined the association of height with prostate cancer among 34268 men in the prostate, lung, colorectal, and ovarian cancer trial. Anthropometry was assessed at baseline and 2144 incident prostate cancer cases were identified upto 8.9 years of follow-up.

Results:

Overall, tallness was not associated with the risk of prostate cancer or with the risk of non-aggressive disease, but the risk for aggressive prostate cancer tended to be greater in taller men (Gleason score ⩾7 or stage ⩾III; P trend=0.05; relative risk (RR) for 190 cm+ vs ⩽170 cm=1.39, 95% confidence interval (95% CI): 0.96–2.01). This association was largely limited to men below the age of 65 years (P trend=0.008; RR for 190 cm+ vs ⩽170 cm=1.76, 95% CI: 1.06–2.93; P for interaction=0.009), although the number of cases was small and risk estimates were somewhat unstable.

Conclusion:

The results of this large prospective prostate cancer screening trial suggest that tallness is associated with increased risk for younger onset aggressive prostate cancer.     

Is daidzein non-metabolizer a high risk for prostate cancer? A case-controlled study of serum soybean isoflavone concentration

BACKGROUND: It has been postulated that soybean isoflavones act as inhibitory factors in prostate cancer. However, to date there have been no case-controlled clinical studies carried out to compare the circulating concentrations of isoflavones in prostate cancer patients and control subjects. METHODS: The serum levels of genistein, daidzein and equol were determined and compared in 253 experimental subjects (141 prostate cancer patients and 112 cancer-free controls). RESULTS: The serum concentrations of isoflavones were compared in hospitalized and non-hospitalized subjects and for both the prostate cancer patients and the controls the concentrations were lower in the hospitalized subjects. The serum concentrations of genistein and daidzein were compared in subjects <70 years of age and subjects >/=70 years old and the levels were significantly lower in the younger group. Contrary to our expectation, comparison of the patient group and the control group revealed the serum concentrations of isoflavones to be higher in the patient group. Daidzein non-metabolizers were compared in the hospitalized experimental subjects of the patient group and the control group and they were significantly more common in the patient group. The poorly differentiated cancer patient group included a significantly lower percentage of daidzein metabolizers. CONCLUSIONS: The above findings revealed that equol itself or some unknown factor regulating the metabolism of daidzein is deeply involved in the biology of prostate cancer. Future studies are urgently needed to compare the incidence of daidzein metabolizers among various countries.     

A prospective study of lifetime physical activity and prostate cancer incidence and mortality

Background:

The possible benefit of lifetime physical activity (PA) in reducing prostate cancer incidence and mortality is unclear.

Methods:

A prospective cohort of 45 887 men aged 45–79 years was followed up from January 1998 to December 2007 for prostate cancer incidence (n=2735) and to December 2006 for its subtypes and for fatal (n=190) prostate cancer.

Results:

We observed an inverse association between lifetime (average of age 30 and 50 years, and baseline age) total PA levels and prostate cancer risk. Multivariate-adjusted incidence in the top quartile of lifetime total PA decreased by 16% (95% confidence interval (CI)=2–27%) compared with that in the bottom quartile. We also observed an inverse association between average lifetime work or occupational activity and walking or bicycling duration and prostate cancer risk. Compared with men who mostly sit during their main work or occupation, men who sit half of the time experienced a 20% lower risk (95% CI=7–31%). The rate ratio linearly decreased by 7% (95% CI=1–12%) for total, 8% (95% CI=0–16%) for localised and 12% (95% CI=2–20%) for advanced prostate cancer for every 30 min per day increment of lifetime walking or bicycling in the range of 30 to 120 min per day.

Conclusions:

Our results suggest that not sitting for most of the time during work or occupational activity and walking or bicycling more than 30 min per day during adult life is associated with reduced incidence of prostate cancer.     

Plasma enterolactone and genistein and the risk of premenopausal breast cancer.

BACKGROUND: The scientific debate on the role of dietary phytoestrogens for prevention of breast cancer is still ongoing. We previously reported an inverse association between dietary phytoestrogen intake and premenopausal breast cancer risk and now examine the relationship with plasma phytoestrogen concentrations. METHODS: We measured enterolactone (mammalian lignan) and genistein (isoflavone) concentrations in plasma samples of 220 premenopausal cases and 237 age-matched controls from a population-based case-control study in Germany. RESULTS: Median plasma enterolactone concentrations in cases and controls were 6.3 and 9.7 nmol/l, respectively, and median genistein concentrations were 4.5 and 3.7 nmol/l, respectively. Premenopausal breast cancer risk decreased with increasing plasma enterolactone concentrations. Adjusted odds ratios (95% confidence intervals) were 0.42 (0.20-0.90) and 0.38 (0.17-0.85) (P for trend 0.007) for women in the third and fourth quartile of plasma enterolactone compared to those in the lowest quartile. There was no significant association between plasma genistein concentration and premenopausal breast cancer risk. CONCLUSION: Using biomarkers of phytoestrogen intake, we confirmed the strong inverse association between enterolactone and premenopausal breast cancer risk as found with dietary intake estimates. This result gives support to the potential role of mammalian lignans for breast cancer prevention among premenopausal women in Western populations.     

Serum phytoestrogens and prostate cancer risk in a nested case-control study among Japanese men

The purpose of this study was to examine whether a high serum concentration of phytoestrogens reduces the risk of prostate cancer in a case-control study nested in a community-based cohort in Japan (Japan Collaborative Cohort (JACC) Study). Information on lifestyles and sera of the subjects were collected in 1988–90, and they were followed up to 1999. Incident and dead cases of prostate cancer and controls were matched for study area and age. Phytoestrogens and sex hormones in sera stored at −80°C were measured in 2002. Of 14,105 male subjects of the cohort who donated their sera, 52 cases and 151 controls were identified. Three datasets were analyzed; 1) all subjects, 2) 40 cases and 101 controls after excluding subjects with low testosterone levels who were suspected of having had medical intervention, and 3) 28 cases and 69 controls with prostate specific antigen level of ∼10.0 ng/ml. The odds ratio (OR) for the highest level to the lowest was 0.38 (95% confidence interval (CI); 0.13, 1.13) for genistein, 0.41 (0.15, 1.11) for daidzein, and 0.34 (0.11, 1.10) for equol for the second dataset. Genistein and daidzein showed similar findings in the third one. Equol and equol/daidzein ratio showed consistent findings in all three datasets (OR=0.39, 95% CI; 0.13, 0.89, trend P=0.02 for the first dataset). Their effects seemed to be independent of serum sex hormones. In conclusion, serum genistein, daidzein, and equol seemed to dose-dependently reduce prostate cancer risk. (Cancer Sci 2004; 95: 65–71)     

Urinary isoflavonoid and lignan excretion on a Western diet: relation to soy, vegetable, and fruit intake.

Dietary isoflavone and lignan phytoestrogens are potential chemopreventive agents. This has led to a need to monitor exposure to these compounds in human populations and to determine which components of a mixed diet contribute to the exposure. Typically, urinary isoflavonoid excretion is associated with soy consumption and that of lignans is associated with whole grains. However, other plant foods are known to contain phytoestrogen precursors. The purpose of this study was to examine the association between urinary isoflavonoid and lignan excretion and intakes of vegetables and fruits (V&F). Isoflavonoids (genistein, daidzein, O-desmethylangolensin, and equol) and lignans (enterolactone, enterodiol, and matairesinol) were measured in urine collected for 3 days from 49 male and 49 female volunteers (age, 18-37 years) reporting a wide range of habitual V&F intakes. Dietary intakes were assessed using 5-day diet records and a food frequency questionnaire. V&F groupings (total V&F, total V, total F, soyfoods, and V&F grouped by botanical families) were used to assess the relationship between V&F intake and urinary isoflavonoid and lignan excretion. Pearson correlations were performed. Intake of soyfoods was correlated significantly with urinary genistein (r = 0.40; P = 0.0001), O-desmethylangolensin (r = 0.37; P = 0.0002), daidzein (r = 034; P = 0.0007), and the sum of isoflavonoids (r = 0.39; P = 0.0001). There was no association between equol excretion and soy intake or between the isoflavonoids and any other V&F groupings. In addition, isoflavonoid excretion was correlated positively with intake of high-fat and processed meats, particularly among men who did not consume soy. This suggests that, even in the United States, on a Western diet, soyfoods are the primary contributors to isoflavone intake; however, additional "hidden sources" of soy may also contribute to exposure. In contrast, a variety of fiber-containing foods contributed to lignan excretion; the sum of the urinary lignans, enterodiol, enterolactone, and matairesinol, was associated with intake of total F (r = 0.27; P = 0.008), total V&F (r = 0.25; P = 0.01), soyfoods (r = 0.28; P = 0.006), and dietary fiber (r = 0.36; P = 0.0003). Overall, urinary phytoestrogens (isoflavonoids + lignans) were significantly higher in "high" compared with "low" V&F consumers. Compared with the "low" V&F group, the "high" group consumed diets that were, on average, higher in fiber and carbohydrate and soyfoods and lower in fat; thus, the urinary phytoestrogens may also be a useful marker of healthier dietary patterns.     

Plasma enterolignans are associated with lower colorectal adenoma risk.

Lignans are biphenolic compounds that occur in foods of plant origin such as whole grains, seeds, fruits and vegetables, and beverages, such as coffee and tea. Plant lignans are converted by intestinal bacteria into the enterolignans, enterodiol and enterolactone. Enterolignans possess several biological activities, whereby they may influence carcinogenesis. We studied the associations between plasma enterolignans and the risk of colorectal adenomas in a Dutch case-control study. Colorectal adenomas are considered to be precursors of colorectal cancer. Cases (n = 532) with at least one histologically confirmed colorectal adenoma and controls (n = 503) with no history of any type of adenoma were included. Plasma enterodiol and enterolactone concentrations were measured by liquid chromatography with tandem mass spectrometry. Associations were stronger for incident than for prevalent cases. When only incident cases (n = 262) were included, high compared to low plasma concentrations of enterodiol were associated with a reduction in colorectal adenoma risk after adjustment for confounding variables. Enterodiol odds ratios (95% confidence intervals) were 1.00, 0.69 (0.42-1.13), 0.60 (0.37-0.99), and 0.53 (0.32-0.88) with a significant trend (P = 0.01) through the quartiles. Although enterolactone plasma concentrations were 10-fold higher, enterolactone's reduction in risk was not statistically significant (P for trend = 0.09). Use of oral antibiotic therapy could decrease the plasma concentrations of enterolactone. Exclusion of antibiotic users resulted in similar odds ratios for both enterolignans, but the association for enterolactone became somewhat stronger (P = 0.05 versus P = 0.09). We observed a substantial reduction in colorectal adenoma risk among subjects with high plasma concentrations of enterolignans, in particular, enterodiol. These findings could be important in the prevention of colorectal adenomas.     

Cancer risks in first-degree relatives of CHEK2 mutation carriers: effects of mutation type and cancer site in proband

It is important to have accurate knowledge of the range of cancers associated with various CHEK2 mutations, and of the lifetime risks of cancer associated with each. We wished to establish the relationship between family history, mutation type and cancer risk in families with a CHEK2 mutation. We obtained a blood sample and pedigree information from 2012 unselected women with breast cancer, from 2007 men with prostate cancer and from 1934 patients with colon cancer, from hospitals throughout Poland. Genetic testing was carried out for four founder CHEK2 mutations on all 5953 specimens and 533 carriers were identified. We estimated the risk to age 75 for any cancer in the 2544 first-degree relatives to be 22.3%. After adjusting for mutation type, the risk of breast cancer was much higher among relatives of probands with breast cancer than among relatives of patients with prostate or colon cancer (HR=3.6; 95% CI=2.1–6.2; P=0.0001). Similarly, the risk of prostate cancer was higher among relatives of probands with prostate cancer than among relatives of patients with breast or colon cancer (HR=4.4; 95% CI=2.2–8.7; P=0.0001) and the risk of colon cancer was higher among relatives of probands with colon cancer than among relatives of patients with prostate or breast cancer (HR=4.2; 95% CI=2.4–7.8; P=0.0001). These analyses suggest that the risk of cancer in a carrier of a CHEK2 mutation is dependent on the family history of cancer.     

Plasma pepsinogens, antibodies against Helicobacter pylori, and risk of gastric cancer in the Shanghai Women's Health Study Cohort

Background:

Circulating pepsinogens can indicate atrophic gastritis, a precursor of gastric cancer. We tested the association between gastric cancer and plasma pepsinogens and antibodies against Helicobacter pylori in a case–control study nested in a prospective cohort.

Methods:

We selected 141 gastric cancer cases and 282 incidence-density sampled controls. Plasma concentrations of pepsinogens 1 and 2 were measured using ELISA kits, and anti-H. pylori antibodies were measured using a kit specific to Chinese strains. Associations were estimated using conditional logistic regression models adjusted for potential confounders.

Results:

Gastric cancer subjects were more likely to be anti-H. pylori positive than controls, 97 vs 92%. A plasma pepsinogen 1 (PG1) concentration <50 ng ml^–1 (15% of cases) was associated with a significantly increased risk of gastric cancer (OR 4.23; (95% CI: 1.86–9.63), whereas a plasma pepsinogen 2 (PG2) concentration >6.6 ng ml^–1 (75% of cases) was also associated with a significantly increased risk of gastric cancer (OR 3.62; (95% CI: 1.85–7.09). We also found that the PG1 : 2 ratio had a nearly linear association with gastric cancer risk.

Conclusion:

Lower plasma PG1 : 2 ratios are associated with a higher risk of gastric cancer. Furthermore, it appears that circulating pepsinogens 1 and 2 may be independently associated with the risk of gastric cancer.     

Serum triglyceride concentrations and cancer risk in a large cohort study in Austria

Background:

Blood lipid levels as part of the metabolic syndrome are thought to be linked to cancer risk. Few epidemiological studies have addressed the association between serum triglyceride (STG) concentrations and cancer risk.

Methods:

Serum triglyceride concentrations were collected in a health investigation (1988–2003). The analyses included 156 153 subjects (71 693 men and 84 460 women), with 5079 incident cancers in men and 4738 cancers in women, and an average of 10.6 years of follow-up. All malignancies were ascertained from the population cancer registry. Multivariate Cox proportional hazard models stratified by age and sex were used to determine adjusted cancer risk estimates and 95% confidence interval (95% CI).

Results:

In men and women combined, higher STG concentrations were associated with increased risk of lung (4th vs 1st quartile: HR, 1.94; 95% CI, 1.47–2.54), rectal (HR, 1.56; 95% CI, 1.00–2.44), and thyroid cancer (HR, 1.96; 95% CI, 1.00–3.84). Serum triglyceride concentrations were inversely associated with non-Hodgkin''s lymphoma. In men, STG concentrations were inversely associated with prostate cancer and positively with renal cancer. In women, STG concentrations were positively associated with gynaecological cancers. Stratification by BMI revealed a higher risk of gynaecological cancers in overweight than in normal weight women. No other associations were found.

Conclusions:

Our findings support the hypothesis that STG concentrations are involved in the pathogenesis of lung, rectal, thyroid, prostate, and gynaecological cancers.     

Red and processed meat consumption and risk of pancreatic cancer: meta-analysis of prospective studies

Background:

Whether red and processed meat consumption is a risk factor for pancreatic cancer remains unclear. We conducted a meta-analysis to summarise the evidence from prospective studies of red and processed meat consumption and pancreatic cancer risk.

Methods:

Relevant studies were identified by searching PubMed and EMBASE databases through November 2011. Study-specific results were pooled using a random-effects model.

Results:

Eleven prospective studies, with 6643 pancreatic cancer cases, were included in the meta-analysis. An increase in red meat consumption of 120 g per day was associated with an overall relative risk (RR) of 1.13 (95% confidence interval (CI)=0.93–1.39; P_{heterogeneity}<0.001). Red meat consumption was positively associated with pancreatic cancer risk in men (RR=1.29; 95% CI=1.08–1.53; P_{heterogeneity}=0.28; five studies), but not in women (RR=0.93; 95% CI=0.74–1.16; P_{heterogeneity}=0.21; six studies). The RR of pancreatic cancer for a 50 g per day increase in processed meat consumption was 1.19 (95% CI=1.04–1.36; P_{heterogeneity}=0.46).

Conclusion:

Findings from this meta-analysis indicate that processed meat consumption is positively associated with pancreatic cancer risk. Red meat consumption was associated with an increased risk of pancreatic cancer in men. Further prospective studies are needed to confirm these findings.