Patrizia Gnagnarella

VALIDATION OF A FOOD-FREQUENCY QUESTIONNAIRE TO ASSESS DIETARY INTAKES IN CANCER STUDIES IN ITALY RESULTS FOR SPECIFIC NUTRIENTS

The validity of a 77-item food-frequency questionnaire (FFQ) developed for a multicenter case-control study on diet and cancer in Italy was assessed. Trained interviewers administered the same FFQ to 452 volunteers from three Italian provinces (Pordenone, Genoa, and Forli) completed in two different seasons, at an interval of 3 to 10 months. For 395 (130 males, 265 females; median age = 52 years; range = 35 to 69 years) volunteers, two 7-day dietary (7-DD) records were available. Average intake obtained by means of the FFQ was overestimated by approximately 18% in comparison with the corresponding values based on the two 7-DD records (reference method). Pearson partial correlation coefficients, adjusted for total energy intake between the nutrient intakes assessed by the FFQ and reference method, ranged from 0.19 for vegetable fat to 0.64 for sugar (median value r = 0.46). The unadjusted deattenuated coefficients, which took into account the interindividual variability of consumption, estimated by means of the two 7-DD records, ranged from 0.29 for vegetable fat to 0.72 for starch (median value r = 0.54). The proportion of subjects correctly classified within the lowest two quintiles ranged between 59% for vegetable fat and vitamin E, and 96% for alcohol, and those correctly classified within the highest two quintiles ranged between 44% for vegetable fat and 94% for alcohol. The average proportion of subjects correctly classified within one quintile was 73%. These data indicate that this FFQ provides valid estimates of intakes for major nutrients, comparable to those reported from other studies in North America and other European countries.

Reproducibility of an Italian food frequency questionnaire for cancer studies. Results for specific nutrients

The reproducibility of measures of the intake of total energy and 27 selected nutrients from a quantitative food frequency questionnaire (FFQ) used in a case-control study on cancer of the breast, ovary, and digestive tract was evaluated. The results of two FFQ administrations at an interval of 3 to 10 months (median = 5.4 months) to 452 volunteers (144 males and 308 females; median age = 50 years) from three Italian provinces (Pordenone, Genoa, and Forì) were compared. Pearson correlation coefficients (r) between crude nutrient intake (unadjusted for energy) ranged from 0.50 for vegetable fat to 0.80 for alcohol, with most values falling between 0.60 and 0.70 (median r = 0.67). Adjustment of nutrient intakes for total energy slightly decreased most coefficients (median r = 0.60). The agreement between the two measurements did not differ substantially by sex, age, education, and interval between interviews. The contribution of specific FFQ components (i.e., frequency-only questions, open questions, portion size, and fat intake pattern) was also assessed separately with respect to the performance and reproducibility of nutrient measures, yielding, in general, very similar results. The seven questions concerning individual fat intake pattern, which were used to modulate the composition of various recipes, led, however, to a significant increase in mean daily intake of vegetable fat, oleic acid, and vitamin E, but a reduction of estimated daily intake of linoleic acid and polyunsaturated fatty acids.(ABSTRACT TRUNCATED AT 250 WORDS)

Flavonoids and Breast Cancer Risk in Italy

Few epidemiologic studies have investigated the potential relation between flavonoids and breast cancer risk. We have applied recently published data on the composition of foods and beverages in terms of six principal classes of flavonoids (i.e., flavanones, flavan-3-ols, flavonols, flavones, anthocyanidines, and isoflavones) on dietary information collected in a large-case control study of breast cancer conducted in Italy between 1991 and 1994. The study included 2,569 women with incident, histologically confirmed breast cancer, and 2,588 hospital controls. Odds ratios (OR) and 95% confidence intervals were estimated by multiple logistic regression models. After allowance for major confounding factors and energy intake, a reduced risk of breast cancer was found for increasing intake of flavones (OR, 0.81, for the highest versus the lowest quintile; P-trend, 0.02), and flavonols (OR, 0.80; P-trend, 0.06). No significant association was found for other flavonoids, including flavanones (OR, 0.95), flavan-3-ols (OR, 0.86), anthocyanidins (OR, 1.09), as well as for isoflavones (OR, 1.05). The findings of this large study of an inverse association between flavones and breast cancer risk confirm the results of a Greek study.

Flavonoids and Colorectal Cancer in Italy

Because of their several biological activities, flavonoids may have an important role in explaining the protective effects of vegetables, fruit, and, possibly, tea against cancer. The potential relation between flavonoids and colorectal cancer risk was investigated using data from a multicentric Italian case-control study, including 1,953 cases of colorectal cancers (1,225 colon cancers and 728 rectal cancers) and 4,154 hospital controls admitted for acute nonneoplastic diseases. We have applied recently published data on the composition of foods and beverages, in terms of six principal classes of flavonoids, on dietary information collected through a validated food-frequency questionnaire. Odds ratios (OR) were estimated by multiple logistic regression models, including terms for sex, age, study center, family history of colorectal cancer, education, alcohol consumption, body mass index, physical activity, and energy intake. A reduced risk of colorectal cancer was found for increasing intake of isoflavones (OR, 0.76, for the highest versus the lowest quintile, Ptrend = 0.001), anthocyanidins (OR, 0.67, Ptrend < 0.001), flavones (OR, 0.78, Ptrend = 0.004), and flavonols (OR, 0.64, Ptrend < 0.001). No significant association was found for flavan-3-ols (OR, 0.98), flavanones (OR, 0.96), and total flavonoids (OR, 0.97). The estimates did not substantially differ for colon and rectal cancers, as well as in strata of sex, age, and body mass index. The findings of this large study provide support for an inverse association of selected classes of flavonoids with colorectal cancer risk. (Cancer Epidemiol Biomarker Prev 2006;15(8):1555–8)

Vitamin D and skin cancer: A meta-analysis

A comprehensive bibliographic search of the literature was conducted to identify studies on Cutaneous Malignant Melanoma (CMM) and non-melanoma skin cancer (NMSC), Vitamin D receptor (VDR) polymorphisms, Vitamin D intake and 25(OH)D serum levels. Fully adjusted risk estimates were found and extracted for the two polymorphisms FokI and BsmI and Vitamin D intake. Ten studies were included in the meta-analysis, with a total of 6805 skin cancer cases. We found an association with CMM for both polymorphisms. The summary relative risks (SRR) for the studies on CMM were: 1.21 (1.03-1.42) and 1.21 (0.95-1.54) for the Ff and ff versus wild-type of FokI, respectively. The SRR for ff versus wild-type became significant with the inclusion of NMSC. The SRR for the studies on CMM were: 0.78 (0.65-0.92) and 0.75 (0.59-0.95) for the Bb and BB versus wild-type of BsmI, respectively. There is also a slight indication of a role of dietary Vitamin D in CMM development. In conclusion, this meta-analysis suggests a possible significant role of VDR FokI and BsmI polymorphism in CMM and NMSC risk. The association with Vitamin D intake is less clear and further studies could be useful to clarify the role of diet.

Intake of specific flavonoids and risk of acute myocardial infarction in Italy

OBJECTIVE As intake of flavonoids has been associated with reduced risk of coronary heart disease but data on the relation with specific classes of flavonoids are scarce, we assessed the relation between dietary intake of specific classes of flavonoids and the risk of acute myocardial infarction (AMI) in an Italian population. DESIGN Case-control study. Dietary information was collected by interviewers on a questionnaire tested for validity and reproducibility. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were obtained by multiple logistic regression models including terms for energy and alcohol intake, as well as sociodemographic factors, tobacco and other major recognised risk factors for AMI. SETTING Milan, Italy, between 1995 and 2003. SUBJECTS Cases were 760 patients, below age 79 years, with a first episode of non-fatal AMI, and controls were 682 patients admitted to hospital for acute conditions unrelated to diet. RESULTS A reduced risk of AMI was found for increasing intake of anthocyanidins (OR=0.45, 95% CI 0.26-0.78 for the highest vs. the lowest quintile, Ptrend=0.003) and flavonols (OR=0.65, 95% CI 0.41-1.02, Ptrend=0.02). A tendency towards reduced risks, although not significant, was observed for flavan-3-ols (OR=0.73, 95% CI 0.48-1.10) and total flavonoids (OR=0.74, 95% CI 0.49-1.14). No meaningful heterogeneity was found between the sexes. No association emerged for other flavonoids, including isoflavones, flavanones and flavones. CONCLUSIONS High intake of anthocyanidins reduced the risk of AMI even after allowance for alcohol, fruit and vegetables, supporting a real inverse association between this class of flavonoids and AMI risk.

Vitamin D receptor polymorphisms and cancer.

It was suggested that vitamin D levels influence cancer development. The vitamin D receptor (VDR) is a crucial mediator for the cellular effects of vitamin D. In fact It has been hypothesized that polymorphisms in the VDR gene affect cancer risk and the relevance of VDR gene restriction fragment length polymorphisms for various types of cancer has been investigated by a great number of studies. However, results from previous studies on the association of VDR polymorphisms with different cancer types are somewhat contradictory, and the role of VDR in the etiology of cancer is still equivocal. We have performed a systematic review of the literature to analyze the relevance of more VDR polymorphisms (Fok1, Bsm1, Taq1, Apa1, and Cdx2) for individual malignancies, including cancer of the skin (melanoma and nonmelanoma skin cancer), ovarian cancer, renal cell carcinoma, bladder cancer, non-Hodgkin lymphoma, leukemia, thyroid carcinoma, esophageal adenocarcinoma, hepatocellular carcinoma, sarcoma, head and neck and oral squamous cell carcinoma. Up to June 2012, we identified 79 independent studies for a total of 52427 cases and 62225 controls. Significant associations with VDR polymorphisms have been reported for prostate (Fok1, Bsm1, Taq1), breast (Fok1, Bsm1, Apa1), colon-rectum (Fok1, Bsm1, Taq1) and skin cancer (Fok1, Bsm1, Taq1). Very few studies reported risk estimates for the other cancer sites. Conflicting data have been reported for most malignancies and at present it is still not possible to make any definitive statements about the importance of the VDR genotype for cancer risk. It seems probable that interactions with other factors such as calcium and vitamin D intake, 25(OH)D plasma levels and UV radiation exposure play a decisive role in cancer risk. To conclude, there is some indication that VDR polymorphisms may modulate the risk of some cancer sites and in future studies VDR genetic variation should be integrated also with prediagnostic indicator of vitamin D status.

Vitamin D receptor polymorphism FokI and cancer risk: a comprehensive meta-analysis

Numerous studies investigated the associations of VDR polymorphisms with various types of cancer, suggesting an influence on cancer risk. FokI is one of the most frequently analysed polymorphisms but the results from single studies are contradictory. We performed a meta-analysis looking at the association between the FokI and all cancer sites and investigating sources of heterogeneity. We identified 77 independent studies up to April 2014. We presented the summary odds ratios (SORs) by cancer sites, ethnicity and study features. We found a significant association between FokI and ovarian cancer for ff genotype versus FF with no heterogeneity: SOR = 1.20 (95% CI: 1.02-1.41, I (2) = 0%). Moreover, we found a significant increased risk of any cancer: SOR = 1.08 (95% CI: 1.01-1.16, I (2) = 58%). A significant increased risk of any cancer is confirmed among Caucasian, among studies in Hardy-Weinberg equilibrium and nested case-control studies. Furthermore, among studies in Hardy-Weinberg equilibrium, skin cancer was found significantly associated with FokI: SOR = 1.24 (95% CI: 1.01-1.54; I (2) = 24%) for ff versus FF. The estimated number of cases attributable to ff genotype is 4221 for ovarian cancer and 52858 for skin cancer worldwide each year. No indication for publication bias was found for any cancer site. In conclusion, we found an overall significant association of FokI polymorphism with any cancer, with differential effect by ethnicity. In particular, the summary estimates indicate an increase risk for ovarian and skin cancer for ff versus FF. However, other factors may act modifying the association, and further studies are needed to clarify the impact on cancer risk.

Vitamin supplement consumption and breast cancer risk: a review

Background: Breast cancer is the most frequently diagnosed cancer globally, and studies provide contradictory results about the possible effects of vitamin supplementation to reduce cancer risk. Our aim was to conduct a review to better investigate whether vitamin supplements given orally modify breast cancer risk. Methods: We conducted a comprehensive, systematic bibliographic search of the medical literature to identify relevant studies. Case-control, cohort studies, and randomised controlled trials (RCTs) published up to August 2013 that reported cancer risk estimates for vitamin supplementation were included. For each study, we retrieved study characteristics, study population, exposure evaluation, and risk estimates. Results: We identified 26 studies (14 cohort, 11 case-control, and one RCT) and overall, we found 104 estimates. We grouped all the estimates into six supplementation categories: vitamin A and beta-carotene, B-group vitamins and folic acid, vitamin C, vitamin D, vitamin E, and multivitamins. Only a few studies showed a statistically significant association between the consumption of supplemental vitamins and the occurrence of breast cancer, and most of the significant estimates were found in case-control studies. The results found in prospective studies seem to be in the opposite direction. Conclusion: The role of vitamin supplements in preventing breast cancer still remains unclear, considering our review. Although biologic mechanisms exist to support the anticancer effects of vitamins, there is no clear evidence for an effect in cancer prevention for vitamin supplements. Further investigations are warranted to elucidate the mechanisms by which vitamin supplementation can modify breast cancer development.

Meta-analysis on vitamin D receptor and cancer risk: focus on the role of TaqI, ApaI, and Cdx2 polymorphisms.

Vitamin D plays a significant role in our health, including cancer incidence and mortality. Vitamin D receptor (VDR) single-nucleotide polymorphisms (SNPs) may affect its activity, influencing the risk of cancer. Several studies have investigated VDR SNPs, but the association with the risk of cancer is controversial. Here, we present a meta-analysis to assess the association of TaqI, ApaI, and Cdx2 SNPs with the risk of cancer. A systematic literature search was performed following a predefined protocol and using validated search strategies. This meta-analysis shows the summary odd ratio (SOR) overall, by cancer sites and by ethnicity. Up to January 2014, we identified 73 independent studies with 35 525 cases and 38 675 controls. The meta-analysis of Cdx2 gg versus GG showed a significant 12% increased risk for all cancers [SOR=1.12; 95% confidence interval (CI): 1.00–1.25]. The other SNPs analyzed did not show an overall significant association with the risk of cancer: SOR=0.98 (95% CI: 0.90–1.07) and 1.06 (95% CI: 0.95–1.19) for TaqI tt versus TT and ApaI aa versus AA, respectively. TaqI shows a significant 43% increased risk for colorectal cancer (SOR=1.43; 95% CI: 1.30–1.58 for tt vs. TT). Strong frequency variations are present among different ethnic groups. This meta-analysis showed an overall increased risk of cancer associated with Cdx2 SNP and a specific higher risk of colorectal cancer associated with the TaqI polymorphism. The VDR genotype might become more relevant when clustered in a specific haplotype, associated with other SNPs of genes involved in vitamin D metabolism, or for specific tumors and/or patient characteristics.