Alcohol intake and ovarian cancer risk: a pooled analysis of 10 cohort studies

Alcohol has been hypothesized to promote ovarian carcinogenesis by its potential to increase circulating levels of estrogen and other hormones; through its oxidation byproduct, acetaldehyde, which may act as a cocarcinogen; and by depletion of folate and other nutrients. Case-control and cohort studies have reported conflicting results relating alcohol intake to ovarian cancer risk. We conducted a pooled analysis of the primary data from ten prospective cohort studies. The analysis included 529 638 women among whom 2001 incident epithelial ovarian cases were documented. After study-specific relative risks (RR) and 95% confidence intervals (CI) were calculated by Cox proportional hazards models, and then were pooled using a random effects model; no associations were observed for intakes of total alcohol (pooled multivariate RR=1.12, 95% CI 0.86-1.44 comparing > or =30 to 0 g day(-1) of alcohol) or alcohol from wine, beer or spirits and ovarian cancer risk. The association with alcohol consumption was not modified by oral contraceptive use, hormone replacement therapy, parity, menopausal status, folate intake, body mass index, or smoking. Associations for endometrioid, mucinous, and serous ovarian cancer were similar to the overall findings. This pooled analysis does not support an association between moderate alcohol intake and ovarian cancer risk.     

Relationship between dietary and supplemental intake of folate,methionine, vitamin B6 and folate receptor α expression in ovarian tumors

Because folate receptor α (FRα) is frequently over‐expressed in epithelial ovarian tumors, we hypothesized that its association with folate may differ by FRα expression or by the timing of intake. We examined the association between folate and other cofactors in 152 ovarian cancers evaluated for FRα expression from the Nurses' Health Study. Multivariate odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression. FRα expression was higher in serous invasive and advanced stage ovarian tumors. Recent dietary folate intake ≥ 300 μg/day compared to < 300 μg/day was associated with decreased risk of developing ovarian cancer (OR = 0.62; 95%CI 0.40–0.96). There was suggestion of an increased risk with total folate (dietary and supplemental) (OR=1.42; 95%CI 0.94–2.14 for past and OR = 1.53; 95%CI 0.99–2.37 for recent intake). These results did not vary by FRα status of the tumor. Methyl group score, a marker of high dietary folate and methionine intake but low alcohol consumption, was inversely associated with risk of ovarian cancer (OR = 0.44; 95%CI 0.23–0.84 for past and OR=0.46; 95%CI 0.24–0.88 for recent intake). There were no clear individual associations between methionine, vitamin B₆, or multivitamin use and ovarian cancer risk overall or by FRα tumor status. Our data do not support the hypothesis that the relationship between factors involved in one‐carbon metabolism and ovarian cancer risk differs by FRα status of the tumor.     

Association of folate and alcohol with risk of ovarian cancer in a prospective study of postmenopausal women

Studies evaluating the association of ovarian cancer with alcohol intake are inconsistent, and few have evaluated this association in the context of folate consumption. Dietary folate and alcohol intakes and lifestyle and medical information were collected with self-administered questionnaires in 1986 from postmenopausal women aged 55–69 followed prospectively for 15 years for risk of epithelial ovarian cancer in the Iowa Women's Health Study. Among 27,205 eligible women free of baseline cancer, 147 incident epithelial ovarian cancer cases were identified by linkage to a cancer registry. Compared to the lowest quartile of total folate (food plus supplement) intake, the multivariable risk ratios (RR) for increasing quartiles were 1.0 (referent), 1.59, 1.24, 1.73 (95% confidence interval [CI], 0.90–3.33; p for trend, 0.20). Compared to non-drinkers, the RRs for increasing alcohol intake were 1.0 (referent), 0.78 for 0.01–3.9 g/d, 0.75 for 4.0–9.9 g/d and 0.58 for 10 g/d (95% CI, 0.30–1.11; p for trend, 0.08). Among women with alcohol intake 4 g/d compared to <4 g/d, the apparent risk reduction was limited to those with total folate intake 331 g/d (RR, 0.52; 95% CI, 0.22–1.19; p for interaction, 0.04) although this estimate was based on only seven cases. The association did not change appreciably when we excluded tumors of mucinous histology. These findings suggest that alcohol consumption is inversely related to postmenopausal ovarian cancer, and that the association of folate with ovarian cancer may vary by the amount of alcohol consumed.     

Caffeine, alcohol, smoking, and the risk of incident epithelial ovarian cancer

BACKGROUND: Smoking, caffeine, and alcohol intake are all potentially modifiable factors that have an unclear association with ovarian cancer risk. Therefore, the associations between these exposures and ovarian cancer risk were prospectively examined among 110,454 women in the Nurses' Health Study (NHS) for the smoking analyses and 80,253 women for the dietary analyses. METHODS: Women completed biennial questionnaires assessing ovarian cancer risk factors beginning in 1976, with food frequency questionnaires administered every 2 to 4 years starting in 1980. For the smoking analyses, 737 confirmed cases of epithelial ovarian cancer were identified and for the dietary aims, 507 cases were identified through June 1, 2004. RESULTS: Compared with never-smokers, neither current nor past smoking was associated with ovarian cancer risk overall; however, both were associated with mucinous tumors (n = 69; rate ratio [RR], past = 2.02 [95% confidence interval (CI), 1.15-3.55]; RR, current = 2.22 [95% CI, 1.16-4.24]). A modest inverse association between caffeine intake and ovarian cancer risk was observed (RR, top vs bottom quintile = 0.80; 95% CI, 0.60-1.07 [P = .03]), which was strongest for women who had never used either oral contraceptives (RR = 0.65; 95% CI, 0.46-0.92 [P for heterogeneity = .02]) or postmenopausal hormones (RR = 0.57; 95% CI, 0.36-0.91 [P for heterogeneity = .13]). Alcohol was not associated with ovarian cancer risk. CONCLUSIONS: The results of the current study suggest that cigarette smoking may only increase the risk for mucinous ovarian tumors, and alcohol intake was not associated with risk. However, an inverse association was observed between caffeine intake and ovarian cancer risk, particularly in women not using hormones; this finding merits further study.     

Does folate intake decrease risk of postmenopausal breast cancer among women with a family history?

BACKGROUND: Several recent studies suggest that adequate dietary folate may attenuate the risk of breast cancer associated with intake of alcohol. We examined whether the putative benefit extends to women with a family history (FH) of breast cancer using a cohort of 33,552 postmenopausal women aged 55-69 years in 1986. METHOD: Folate and alcohol intake was estimated from a food frequency questionnaire completed at baseline. Folate was categorized as upper 50th, 31st-50th, 11th-30th, and <10th percentiles. Alcohol use was initially classified into three levels; never drinkers, less than the median and greater than the median. Subsequent models collapsed levels of intake to any versus none. Occurrence of breast cancer was determined through linkage to the Iowa SEER registry. Multivariate-adjusted relative risks (RR) and 95% confidence intervals (CI) were estimated through Cox proportional hazards regression, stratified on FH using non-drinkers with high folate and no FH as the referent group. RESULTS: Through 14 years, 1823 incident cases were identified, 308 among FH+ women. Among FH- women, low folate was not a risk factor among non-drinkers (RR = 0.96, CI = 0.73-1.26), but was among drinkers (RR = 1.40, CI = 1.05-1.86). Drinkers with high folate were not at elevated risk (RR = 1.03, CI = 0.89-1.19). Among FH+ women, low folate was a risk factor among drinkers (RR = 2.21, CI = 1.43-3.41) and non-drinkers (RR = 2.39, CI = 1.36-4.20). Further, drinkers with high folate remained at increased risk (RR = 1.67, CI= 1.30-2.14). However, FH+ women with high folate who did not drink alcohol had no elevated risk. CONCLUSION: These results suggest that folate may attenuate the risks of postmenopausal breast cancer associated with family history, but only if alcohol use is avoided or minimized.     

Alcohol, wine, and risk of epithelial ovarian cancer.

Moderate alcohol intake can influence sex hormone levels and affect ovarian function as well as increasing breast cancer risk. This suggests that alcohol might also influence ovarian cancer risk. We have evaluated this among 696 Australian women with histologically confirmed epithelial ovarian cancer and 786 cancer-free control women, selected at random from the electoral roll. Sociodemographic information and a detailed reproductive history were collected in a face-to-face interview, and information about diet and alcohol consumption was obtained from a food frequency questionnaire. Logistic regression was used to calculate adjusted odds ratios (OR) and 95% confidence intervals (95% CI). Overall, 59% of women drank <1 standard drink/week and only 5% of cases and 8% of controls drank an average of > or =2 standard drinks/day. Compared with nondrinkers, the OR for women who drank an average of > or =2 standard drinks/day was 0.49 (95% CI = 0.30-0.81). This effect did not vary for the different subtypes but was restricted to wine (OR = 0.56, 95% CI = 0.33-0.93 for > or =1 glass/day versus nondrinkers) with no effect for beer (OR = 1.26, 95% CI = 0.65-2.46) or sherry/spirits (OR = 1.07, 95% CI = 0.59-1.95). Combining our results with the six previous population-based studies gave a pooled OR of 0.72 (95% CI = 0.54-0.97) for the highest alcohol intake group versus nondrinkers. These data suggest that alcohol does not increase risk of ovarian cancer. In this Australian population, the inverse association with alcohol was due solely to wine consumption and so may be a consequence of antioxidants and/or phytoestrogens in wine rather than the alcohol itself.     

Dietary folate intake and k-ras mutations in sporadic colon and rectal cancer in The Netherlands Cohort Study

We studied the association between dietary folate and specific K-ras mutations in colon and rectal cancer in The Netherlands Cohort Study on diet and cancer. After 7.3 years of follow-up, 448 colon and 160 rectal cancer patients and 3,048 sub-cohort members (55-69 years at baseline) were available for data analyses. Mutation analysis of the K-ras gene was carried out on all archival adenocarcinoma specimens. Case-cohort analyses were used to compute adjusted incidence rate ratios (RR) and 95% confidence intervals (CI) for colon and rectal cancer overall and for K-ras mutation status subgroups according to 100 mug/day increased intake in dietary folate. Dietary folate intake was not significantly associated with colon cancer risk for men or women, neither overall nor with K-ras mutation status. For rectal cancer, folate intake was associated with a decreased disease risk in men and was most pronounced for K-ras mutated tumors, whereas an increased association was observed for women. Regarding the K-ras mutation status in women, an increased association was observed for both wild-type and mutated K-ras tumors. Specifically, folate intake was associated with an increased risk of G>T and G>C transversions in rectal tumors (RR = 2.69, 95% CI = 1.43-5.09), but inversely associated with G>A transitions (RR = 0.08, 95% CI = 0.01-0.53). Our data suggest that the effect of folate on rectal cancer risk is different for men and women and depends on the K-ras mutation status of the tumor.     

5,10-Methylenetetrahydrofolate reductase codon 677 and 1298 polymorphisms and colon cancer in African Americans and whites.

We evaluated polymorphisms in methylenetetrahydrofolate reductase (MTHFR), folate intake and alcohol consumption in relation to risk of colon cancer in a population-based case-control study in North Carolina. The study included 555 cases (244 African Americans and 311 whites) and 875 controls (331 African Americans and 544 whites). Total folate intake of <400 versus > or =400 microg/day showed a weak positive association with colon cancer among both African Americans [adjusted odds ratio (OR) = 1.4, 95% confidence interval (CI) = 1.0-2.0] and whites (OR = 1.6, 95% CI = 1.2-2.2). No association was observed with use of alcohol. Compared with wild-type genotypes, there was no association between the low activity MTHFR codon 677 TT genotype and colon cancer, but the low activity codon 1298 CC genotype was inversely associated with colon cancer in whites (OR = 0.5, 95% CI = 0.3-0.9). Unlike previous studies, we did not observe a strong protective effect of the codon 677 TT low-activity genotype when folate intake was high. Instead, we observed an increased risk of colon cancer when folate intake was low for participants with wild- type genotypes. Adjusted ORs for the combined effects of codon 677 CC and codon 1298 AA genotypes and folate intake <400 microg/day were 1.9 (95% CI = 1.1-3.4) in African Americans and 2.5 (95% CI = 1.2-5.2) in whites. Our results suggest that variation at MTHFR codon 1298 (within the COOH-terminal region) may be more important for colon cancer than variation at codon 677 (NH(2)-terminal region), and in populations where folate intake is low, wild-type MTHFR activity may increase risk for colon cancer.     

Genetic variation in the one-carbon transfer pathway and ovarian cancer risk

Dysfunction in enzymes involved in one-carbon (1-C) metabolism can lead to increased chromosomal strand breaking and abnormal methylation patterns, which are both associated with cancer risk. Availability of 1-C units may modify risk. We investigated the association of single-nucleotide polymorphisms (SNP) in 21 genes in the 1-C transfer pathway among 829 Caucasian cases with primary epithelial ovarian cancer and 941 frequency-matched unaffected controls enrolled at Mayo Clinic (Rochester, MN) and Duke University (Durham, NC) and examined risk modification by multivitamin supplement use. Multivariable-adjusted SNP-specific logistic regression and haplotype analyses were done for 180 SNPs and false positive report probabilities (FPRP) were calculated. Each copy of the minor allele in SHMT1 intron 5 A>G (rs9909104) was associated with epithelial ovarian cancer [odds ratio (OR), 1.2; 95% confidence interval (95% CI), 1.0-1.4; P trend = 0.02; FPRP = 0.16] and a 5-SNP SHMT1 haplotype was associated with decreased risk (P = 0.01; FPRP = 0.09). Three SNPs in DNMT3A were associated with risk among multivitamin supplement users: 3' untranslated region (UTR) C>G (rs13420827: OR, 0.8; 95% CI, 0.6-1.0; P interaction = 0.006; FPRP = 0.54), intron 6 G>A (rs11887120: OR, 0.8; 95% CI, 0.7-1.0; P interaction = 0.007; FPRP = 0.57), and intron 22 A>T (rs11695471: OR, 1.2; 95% CI, 1.0-1.5; P interaction = 0.01; FPRP = 0.66). These data extend previous findings from other cancers of a role for SHMT1 in ovarian cancer, and provide evidence that SNPs in methylation and DNA synthesis reactions are associated with risk of ovarian cancer. Interventions with modifiable factors such as multivitamin intake may reduce risk.     

Dietary folate consumption and risk of ovarian cancer: a prospective cohort study.

Deficient dietary folate intake may be associated with increased cancer risk in humans owing to DNA damage resulting from impaired nucleotide excision repair. It is conceivable that an association with folate may be modified by alcohol and/or methionine intake given that alcohol consumption and low methionine intakes both increase dietary folate requirements. In the cohort study reported here, we examined the association between dietary folate intake and ovarian cancer risk, overall and within strata defined by alcohol and methionine intakes. The investigation was conducted in 49 613 Canadian women who were participants in the National Breast Screening Study and who completed self-administered lifestyle and food frequency questionnaires between 1980 and 1985. Linkages to cancer and national mortality databases yielded data on cancer incidence and deaths among cohort members, with follow-up ending between 1998 and 2000. During a mean 16.4 years of follow-up, we observed 264 incident ovarian cancer cases among 48 766 women for whom data were available. Dietary folate intake was associated with a 25% decrease in risk of ovarian cancer for the highest versus the lowest quartile level of intake (hazard ratio=0.75, 95% confidence interval=0.42-1.34, Ptrend=0.25). On stratification by alcohol intake, dietary folate was not associated with ovarian cancer risk among women consuming <4 g/day of alcohol, but there was some suggestion of reduced risk at relatively high levels of folate intake among women consuming > or =4 g/day of alcohol/day (Ptrend=0.09; Pinteraction=0.22). The association between folate and ovarian cancer risk did not vary by strata of methionine intake (Pinteraction=0.98). Our findings, while not statistically significant, suggest that relatively high dietary folate intake may be associated with a reduction in ovarian cancer risk among women with relatively high alcohol consumption and among those with relatively high methionine intake.     

Folate intake and risk of breast cancer characterized by hormone receptor status.

Folate plays an important role in DNA methylation, and aberrant methylation of the estrogen receptor (ER) gene may be related to the loss of ER gene expression in breast tumors. Thus, deficient folate status has been hypothesized to be associated primarily with ER gene-negative breast tumors, but data relating folate intake to breast cancer risk according to ER status are sparse. We conducted a prospective cohort analysis of folate intake among 88,744 women in the Nurses' Health Study who completed a food frequency questionnaire in 1980 and every 2 to 4 years thereafter. During 20 years of follow-up, 2,812 ER+ and 985 ER- invasive breast cancer cases were documented. Higher total folate intake was significantly associated with lower risk of developing ER- but not ER+ breast cancer; the multivariable relative risks (RR) and 95% confidence intervals (95% CI) comparing the highest to the lowest quintile were 0.81 (0.66-0.99) for ER- tumors and 1.00 (0.89-1.14) for ER+ tumors. The inverse association between total folate intake and ER- breast cancer was mainly present among women consuming at least 15 g/d of alcohol (multivariable RR, 0.46; 95% CI,=0.25-0.86; top versus bottom quintile). These findings support the hypothesis that higher folate intake reduces the risk of developing ER- breast cancer. Ensuring adequate folate intake seems particularly important for women at higher risk of breast cancer because of alcohol consumption.     

A prospective study of dietary flavonoid intake and incidence of epithelial ovarian cancer

Flavonoids are antioxidant compounds found in plants, including fruits, vegetables and tea. No prior prospective studies have examined the association between intake of flavonoids in the flavonol and flavone subclasses and ovarian cancer risk. We analyzed the association between intake of 5 common dietary flavonoids and incidence of epithelial ovarian cancer among 66,940 women in the Nurses' Health Study. We calculated each participant's intake of myricetin, kaempferol, quercetin, luteolin and apigenin from dietary data collected at multiple time points, and used Cox proportional hazards regression to model the incidence rate ratio (RR) of ovarian cancer for each quintile of intake. Our analysis included 347 cases diagnosed between 1984 and 2002, and 950,347 person-years of follow-up. There was no clear association between total intake of the 5 flavonoids examined and incidence of ovarian cancer (RR = 0.75 for the highest versus lowest quintile, 95% confidence interval [CI] = 0.51-1.09). However, there was a significant 40% decrease in ovarian cancer incidence for the highest versus lowest quintile of kaempferol intake (RR = 0.60, 95% CI = 0.42-0.87; p-trend = 0.002), and a significant 34% decrease in incidence for the highest versus lowest quintile of luteolin intake (RR = 0.66, 95% CI = 0.49-0.91; p-trend = 0.01). There was evidence of an inverse association with consumption of tea (nonherbal) and broccoli, the primary contributors to kaempferol intake in our population. These data suggest that dietary intake of certain flavonoids may reduce ovarian cancer risk, although additional prospective studies are needed to further evaluate this association. If confirmed, these results would provide an important target for ovarian cancer prevention.     

Alcohol, folate, methionine, and risk of incident breast cancer in the American Cancer Society Cancer Prevention Study II Nutrition Cohort.

Recent studies suggest that the increased risk of breast cancer associated with alcohol consumption may be reduced by adequate folate intake. We examined this question among 66,561 postmenopausal women in the American Cancer Society Cancer Prevention Study II Nutrition Cohort. A total of 1,303 incident cases had accrued during the first 5 years of follow-up. Cox proportional hazards models and stratified analysis were used to examine the relationship between alcohol, dietary and total folate intake, multivitamin use, dietary methionine, and breast cancer. We observed an increasing risk of breast cancer with increasing alcohol consumption (P for trend = 0.01). In the highest category of consumption (15 or more grams of ethanol/day), the risk of breast cancer was 1.26 (95% confidence interval, 1.04-1.53) compared with nonusers. We observed this association with higher alcohol consumption for in situ, localized, and regional disease. We found no association between risk of breast cancer and dietary folate, total folate, multivitamin use, or methionine intake. Furthermore, we found no evidence of an interaction between levels of dietary folate (P for interaction = 0.10) or total folate (P for interaction = 0.61) and alcohol. Nor did we find evidence of an interaction between alcohol consumption and recent or long-term multivitamin use (P for interaction = 0.27). Our results are consistent with a positive association with alcohol but do not support an association with folate or methionine intake or an interaction between folate and alcohol intake on risk of breast cancer.     

Plasma folate,vitamin B6, vitamin B12, homocysteine,and risk of breast cancer

BACKGROUND: In several epidemiologic investigations, folate intake has appeared to reduce the elevated risk of breast cancer associated with moderate alcohol consumption. However, data relating plasma folate levels to breast cancer risk are sparse. We investigated the association between plasma folate and other vitamins with breast cancer in a prospective, nested case-control study. METHODS: Blood samples were obtained during 1989 and 1990 from 32 826 women in the Nurses' Health Study who were followed through 1996 for the development of breast cancer. We identified 712 breast cancer case patients and selected 712 individually matched control subjects. Dietary information was obtained using food frequency questionnaires given in 1980, 1984, 1986, and 1990. Logistic regression was used to estimate the relative risks (RRs) of breast cancer (after adjustment for potential risk factors), and a generalized linear model was used to calculate the Pearson correlation coefficients between plasma estimates of folate, vitamin B(6), vitamin B(12), and homocysteine, and intakes of folate, vitamin B(6), and vitamin B(12). All statistical tests were two-sided. RESULTS: The multivariable RR comparing women in the highest quintile of plasma folate with those in the lowest was 0.73 (95% confidence interval [CI] = 0.50 to 1.07; P(trend) =.06). The inverse association between plasma folate and breast cancer risk was highly statistically significant among women consuming at least 15 g/day (i.e., approximately 1 drink/day) of alcohol (multivariable RR = 0.11, 95% CI = 0.02 to 0.59 for highest versus lowest quintile) in contrast with that of women consuming less than 15 g/day (multivariable RR = 0.72, 95% CI = 0.49 to 1.05). The multivariable RR comparing women in the highest quintile of plasma vitamin B(6) levels with those in the lowest quintile was 0.70 (95% CI = 0.48 to 1.02; P(trend) =.09). Plasma vitamin B(12) levels were inversely associated with breast cancer risk among premenopausal women (multivariable RR = 0.36, 95% CI = 0.15 to 0.86 for highest versus lowest quintile) but not among postmenopausal women. Plasma homocysteine was not associated with breast cancer risk. CONCLUSIONS: Higher plasma levels of folate and possibly vitamin B(6) may reduce the risk of developing breast cancer. Achieving adequate circulating levels of folate may be particularly important for women at higher risk of developing breast cancer because of higher alcohol consumption.     

Fruits and vegetables and ovarian cancer risk in a pooled analysis of 12 cohort studies.

Because fruits and vegetables are rich in bioactive compounds with potential cancer-preventive actions, increased consumption may reduce the risk of ovarian cancer. Evidence on the association between fruit and vegetable intake and ovarian cancer risk has not been consistent. We analyzed and pooled the primary data from 12 prospective studies in North America and Europe. Fruit and vegetable intake was measured at baseline in each study using a validated food-frequency questionnaire. To summarize the association between fruit and vegetable intake and ovarian cancer, study-specific relative risks (RR) were estimated using the Cox proportional hazards model, and then combined using a random-effects model. Among 560,441 women, 2,130 cases of invasive epithelial ovarian cancer occurred during a maximum follow-up of 7 to 22 years across studies. Total fruit intake was not associated with ovarian cancer risk-the pooled multivariate RR for the highest versus the lowest quartile of intake was 1.06 [95% confidence interval (95% CI), 0.92-1.21; P value, test for trend = 0.73; P value, test for between-studies heterogeneity = 0.74]. Similarly, results for total vegetable intake indicated no significant association (pooled multivariate RR, 0.90; 95% CI, 0.78-1.04, for the highest versus the lowest quartile; P value, test for trend = 0.06; P value, test for between-studies heterogeneity = 0.31). Intakes of botanically defined fruit and vegetable groups and individual fruits and vegetables were also not associated with ovarian cancer risk. Associations for total fruits and vegetables were similar for different histologic types. These results suggest that fruit and vegetable consumption in adulthood has no important association with the risk of ovarian cancer.     

Consumption of vegetables and fruits and risk of ovarian carcinoma

BACKGROUND: To the authors' knowledge, only a few prospective studies to date have investigated the correlation between vegetable and fruit consumption and the risk of ovarian carcinoma and their results have been inconclusive. METHODS: Vegetable and fruit intake was assessed in relation to ovarian carcinoma, among 62,573 postmenopausal women participating in The Netherlands Cohort Study on Diet and Cancer. Women reported on dietary habits and on other risk factors for cancer in a self-administered questionnaire in 1986. Follow-up of cancer was implemented by annual record linkage with The Netherlands Cancer Registry and a pathology register. After 11.3 years of follow-up, data regarding 252 incident invasive epithelial ovarian carcinoma cases and of 2216 subcohort members were available for case-cohort analyses. RESULTS: Multivariable-adjusted rate ratios (RR) of ovarian carcinoma for women in the highest compared with the lowest quintile of intake (RR(Q5 vs. Q1)) were 0.98 (95% confidence interval [95% CI], 0.61-1.58) for total vegetables and 1.11 (95% CI, 0.70-1.78) for total fruit. The RR(Q5 vs. Q1) values of ovarian carcinoma with intake of cooked vegetables, raw vegetables, brassicas, legumes, cooked leafy vegetables, and raw leafy vegetables were 1.35 (95% CI, 0.83-2.21), 0.75 (95% CI, 0.48-1.18), 1.42 (95% CI, 0.88-2.29), 0.93 (95% CI, 0.60-1.44), 1.05 (95% CI, 0.66-1.67), and 1.23 (95% CI, 0.75-2.02), respectively. With the exception of raw endive (multivariable-adjusted RR, 0.24; 95% CI, 0.07-0.78), none of the individual vegetable or fruit items showed a statistically significant association with ovarian carcinoma. CONCLUSIONS: The results of the current study did not support a significant association between vegetable or fruit consumption and ovarian carcinoma risk in a cohort of postmenopausal women.     

Gestational age and fetal growth in relation to maternal ovarian cancer risk in a Swedish cohort.

BACKGROUND: Pregnancy influences subsequent maternal ovarian cancer risk. To date, there is limited evidence whether two characteristics of pregnancy, gestational age and birth weight, could modify risk. MATERIALS AND METHODS: We studied 1.1 million Swedish women who delivered singleton births between 1973 and 2001. Information on infant gestational age and birth weight was abstracted from the nationwide Swedish Birth Register. Women were followed prospectively through linkage with other population-based registers for occurrence of ovarian cancer, death, or emigration through 2001. Hazard ratios [relative risk (RR), 95% confidence interval (95% CI)] from Cox models were used to estimate associations between gestational age, birth weight, and epithelial ovarian cancer risk. RESULTS: During 12.6 million person-years, 1,017 epithelial ovarian cancers occurred. Mean age at diagnosis was 43 years. Compared with women with term deliveries (>/=40 weeks), women with moderately (35-36 weeks) or very (<35 weeks) preterm deliveries had increased risks of epithelial ovarian cancer (RR 1.4, 95% CI 1.0-2.0 and RR 2.3, 95% CI 1.3-3.8, respectively). In contrast, women giving birth to small-for-gestational-age babies had a reduced risk (RR 0.7, 95% CI 0.4-1.0). Stratifying on birth weight and gestational age, there was a strong protective effect of low birth weight on maternal risk of epithelial ovarian cancer among term deliveries, whereas birth weight seemed to have little effect among preterm births (P(interaction) = 0.022). CONCLUSIONS: Our results lend further support that the hormonal milieu of a pregnancy may modify long-term risk of developing ovarian cancer. 32).     

Height, body mass index, and ovarian cancer: a pooled analysis of 12 cohort studies.

BACKGROUND: Although many studies have investigated the association between anthropometry and ovarian cancer risk, results have been inconsistent. METHODS: The associations of height, body mass index (BMI), and ovarian cancer risk were examined in a pooled analysis of primary data from 12 prospective cohort studies from North America and Europe. The study population consisted of 531,583 women among whom 2,036 epithelial ovarian cancer cases were identified. To summarize associations, study-specific relative risks (RR) were estimated using the Cox proportional hazards model and then combined using a random-effects model. RESULTS: Women with height > or =1.70 m had a pooled multivariate RR of 1.38 [95% confidence interval (95% CI), 1.16-1.65] compared with those with height <1.60 m. For the same comparison, multivariate RRs were 1.79 (95% CI, 1.07-3.00) for premenopausal and 1.25 (95% CI, 1.04-1.49) for postmenopausal ovarian cancer (P(interaction) = 0.14). The multivariate RR for women with a BMI > or =30 kg/m(2) was 1.03 (95% CI, 0.86-1.22) compared with women with a BMI from 18.5 to 23 kg/m(2). For the same comparison, multivariate RRs were 1.72 (95% CI, 1.02-2.89) for premenopausal and 1.07 (95% CI, 0.87-1.33) for postmenopausal women (P(interaction) = 0.07). There was no statistically significant heterogeneity between studies with respect to height or BMI. BMI in early adulthood was not associated with ovarian cancer risk. CONCLUSION: Height was associated with an increased ovarian cancer risk, especially in premenopausal women. BMI was not associated with ovarian cancer risk in postmenopausal women but was positively associated with risk in premenopausal women.     

Intake of flavonoids and risk of cancer in Finnish men: The Kuopio Ischaemic Heart Disease Risk Factor Study

Limited amount of evidence suggests that high intake of flavonoids could be associated with decreased risk of lung and colorectal cancer, but more studies are needed. In this prospective cohort study, we assessed the relation between the intakes of 26 flavonoids from 5 subclasses; flavonols, flavones, flavanones, flavan-3-ols and anthocyanidins, and the risk of lung, prostate and colorectal cancer. The study population consisted of 2,590 middle-aged eastern Finnish men of the prospective population-based Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study. The mean intake of flavonoids was 131.0 +/- 214.7 mg/day. During the mean follow-up time of 16.2 years, 62 lung, 138 prostate, and 55 colorectal cancers occurred. All lung cancer cases occurred among either current smokers (n = 50) or previous smokers (n = 12). After adjustment for age, examination years, body mass index, smoking status, pack-years of smoking, physical activity and intakes of alcohol, total fat, saturated fat, fiber, vitamin C and E, relative risk (RR) for lung cancer was 0.27 (95% CI: 0.11-0.66) for the highest quarter of total flavonoid intake as compared with the lowest quarter. Out of 5 flavonoid subclasses, flavonols and flavan-3-ols were associated with lung cancer, for the highest quarter of intake the RR were 0.29 (95% CI: 0.11-0.78) and 0.24 (95% CI: 0.09-0.64), respectively. No association between flavonoid intake and risk of prostate or colorectal cancer were found. We conclude that high intake of flavonoids is associated with decreased risk of lung cancer in middle-aged Finnish smoking men.     

A comparative case-control study of colorectal cancer and adenoma

We conducted a comparative case-control study of colorectal cancer and adenoma involving 221 cases with colorectal cancer, 525 cases with colorectal adenoma and 578 neighborhood controls. Daily vegetables intake was associated with lower risks of distal colon adenoma (relative risks (RR) = 0.59, 95% confidence interval (CI): 0.39-0.89) and rectal cancer (RR = 0.46, 95% CI: 0.25-0.84). Daily beans intake was associated with lower risk of colon adenoma (RR = 0.58, 95% CI: 0.37-0.91 for the proximal colon and RR = 0.63, 95% CI: 0.45-0.88 for the distal colon) and daily intake of seaweeds was associated with lower risk of rectal cancer (RR = 0.42, 95% CI: 0.22-0.82). Daily intake of fish and shellfish also showed an inverse association with the risk of colon adenoma (RR = 0.67, 95% CI: 0.45-0.99 for the proximal colon and RR = 0.70, 0.52-0.94 for the distal colon). Generally, intakes of animal or vegetable fat-rich foods, especially meats, were associated with decreases in risks of both adenoma and cancer, though the association of cancer was not statistically significant. Other than dietary factors, daily alcohol drinking was associated with an increased risk of adenoma in the proximal colon (RR = 1.95, 95% CI: 1.15-3.29) and ex-drinkers showed higher risks for colon adenoma and colorectal cancer. Sports or occupational activities and coffee drinking were inversely associated and family history of colorectal cancer was positively associated with the risk of both colorectal adenoma and cancer.