Italian Case-control Study Research Articles

Gender differences in the VDR-FokI polymorphism and conventional non-genetic risk factors in association with lumbar spine pathologies in an Italian case-control study.

Recently, the FokI polymorphism (rs2228570) in the vitamin D receptor gene (VDR) and conventional risk factors were associated with spine disorders in the Italian population, but without gender analysis. Two-hundred and sixty-seven patients (149 males, 118 females) with lumbar spine disorders were assessed by magnetic resonance imaging (MRI) and 254 (127 males, 127 females) asymptomatic controls were enrolled. The exposure to putative risk factors was evaluated and FokI polymorphism was detected by PCR-restriction fragment length polymorphism (PCR-RFLP). An association between lumbar spine pathologies and higher than average age; overweight; family history; lower leisure physical activity; smoking habit; higher number of hours/day exposure to vibration and more sedentary or intense physical job demand was observed in male patients. In contrast, in females, only higher age, overweight, family history and lower leisure physical activity were risk factors. FF genotype was a 2-fold risk factor to develop discopathies and/or osteochondrosis concomitant with disc herniation for both gender patients, while heterozygous Ff was protective for females only. In males only ff genotype was protective for discopathies and/or osteochondrosis and F allele was a 2-fold risk factor for hernia; discopathies; discopathies and/or osteochondrosis. Sex-related differences in voluntary behaviors, exposure to environmental risks and genetic background could be crucial for a gender-differentiated management of patients with spine disorders.

Childhood leukemia and 50 Hz magnetic fields: findings from the Italian SETIL case-control study.

We report on an Italian case-control study on childhood leukemia and exposure to extremely low frequency magnetic fields (ELF-MF). Eligible for inclusion were 745 leukemia cases, aged 0–10 years at diagnosis in 1998–2001, and 1475 sex- and age-matched population controls. Parents of 683 cases and 1044 controls (92% vs. 71%) were interviewed. ELF-MF measurements (24–48 h), in the child’s bedroom of the dwelling inhabited one year before diagnosis, were available for 412 cases and 587 controls included in the main conditional regression analyses. The magnetic field induction was 0.04 μT on average (geometric mean), with 0.6% of cases and 1.6% of controls exposed to >0.3 μT. The impact of changes in the statistical model, exposure metric, and data-set restriction criteria was explored via sensitivity analyses. No exposure-disease association was observed in analyses based on continuous exposure, while analyses based on categorical variables were characterized by incoherent exposure-outcome relationships. In conclusion, our results may be affected by several sources of bias and they are noninformative at exposure levels >0.3 μT. Nonetheless, the study may contribute to future meta- or pooled analyses. Furthermore, exposure levels among population controls are useful to estimate attributable risk.

Nutrient-based dietary patterns and endometrial cancer risk: an Italian case–control study

Diet has been suggested to have a role on endometrial cancer risk, but few data are available on the role of dietary patterns on this neoplasm. A case–control study was carried out in Italy, including 454 women with endometrial cancer and 908 hospital controls admitted to the same hospitals for acute, non-neoplastic diseases. Dietary information was based on a reproducible and valid food frequency questionnaire. A posteriori dietary patterns were obtained using principal component factor analysis on 28 nutrients. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were obtained from multiple logistic regression models conditioned on age and study center, and adjusted for major known confounding factors. Positive associations were found for the “Western-type diet” (OR=1.63, 95% CI: 1.12–2.38, for the highest versus the lowest quartile category) and the “Animal-derived nutrients and polyunsaturated fatty acids” patterns (OR=1.76, 95% CI: 1.23–2.52). The corresponding risk estimates among women with a body mass index ≥30 were 2.08 (95% CI: 0.92–4.69) and 2.30 (95% CI: 1.03–5.16) for the two patterns, respectively. No association was found for the other three patterns (i.e., “Vitamins and fiber”, OR=0.96, 95% CI: 0.67–1.37, “Starch-rich”, OR=0.99, 95% CI: 0.69–1.42, and “Other fats”, OR=1.03, 95% CI: 0.70–1.52). This study indicates that dietary habits characterized by high intakes of animal products increase endometrial cancer risk, the association being appreciably stronger for obese women.

Dietary inflammatory index and risk of pancreatic cancer in an Italian case-control study.

Previous studies have shown that various dietary components may be implicated in the aetiology of pancreatic cancer. However, the possible relationship between diet-related inflammation and the risk of pancreatic cancer has not yet been investigated. We examined the ability of a newly developed literature-derived dietary inflammatory index (DII) to predict the risk of pancreatic cancer in a case-control study conducted in Italy between 1991 and 2008. This included 326 incident cases and 652 controls admitted to the major teaching and general hospitals for non-neoplastic diseases, frequency-matched to cases by study centre, sex and age. The DII was computed based on dietary intake assessed using a validated and reproducible seventy-eight-item FFQ. Logistic regression models were used to estimate multivariable OR adjusted for age, sex, study centre, education, BMI, smoking status, alcohol drinking and history of diabetes. Energy adjustment was performed using the residual method. Subjects with higher DII scores (i.e., representing a more pro-inflammatory diet) had a higher risk of pancreatic cancer, with the DII being used as both a continuous variable (ORcontinuous 1.24, 95% CI 1.11, 1.38) and a categorical variable (i.e., compared with the subjects in the lowest quintile of the DII, those in the second, third, fourth and fifth quintiles had, respectively, OR(quintile2 v. 1) 1.70, 95% CI 1.02, 2.80; OR(quintile3 v. 1) 1.91, 95% CI 1.16, 3.16; OR(quintile4 v. 1) 1.98, 95% CI 1.20, 3.27; OR(quintile5 v. 1) 2.48, 95% CI 1.50, 4.10; P trend= 0.0015). These data suggest that a pro-inflammatory diet increases the risk of pancreatic cancer.

HPV infection and triple-negative breast cancers: an Italian case-control study.

BackgroundBreast cancer is one of the most important neoplasia among women. To reduce its incidence and mortality impact it would be desirable to early identify risk factors associated with its development. It was recently suggested that biological agents could be the etiological cause, particularly Human Papilloma Virus (HPV). No specific relationship with different breast cancer types has been demonstrated until now. In particular, the triple-negative breast cancer (TNBC), characterized by a receptor negative pattern (ER/PgR/HER2–negative) and poor prognosis, can represent one of the most relevant clinical and public health priority in terms of observational research.FindingsAim of the study was to evaluate the HPV-positivity prevalence in two breast cancer series (TNBC vs. non-TNBC) in Northern Sardinia, Italy. The sample size of each group was represented by 40 formalin-fixed and paraffin-embedded specimens. The mean age was 60.3 years. The majority of the cancers were ductal (84%). The grading distribution was different: G2 was the most prevalent grade in the non-TNBC series, whereas G3 was the most frequent in the TNBC series (70% and 72%, respectively). Six biological samples were HPV-positive (7.5%): the positivity was assessed only in the TNBC group (15%; p-value: 0.026). The isolated genotypes were: 16, 31, 45, 52, 6, and 66. Only one co-infection was found (i.e., HPV-6 and -66).ConclusionsThe prevalence of HPV-positivity in TNBC specimens was 15%. On the basis of its carcinogenetic ability, an etiological role in the pathogenesis of the cancer could be supposed. This association should be confirmed with longitudinal studies to better assess the role of the HPV infection in TNBC and non-TNBC tumors.

Allium vegetable intake and gastric cancer: a case-control study and meta-analysis.

To provide new epidemiological data and summarize evidence on the association between allium vegetable intake and gastric cancer risk. Data were from an Italian case-control study including 230 cases and 547 controls. Odds ratios were derived using multiple logistic regression. We combined results from all published studies using random-effect models. In our case-control study, the odds ratios were 0.59 (95% confidence interval, CI, 0.25-1.41) for ≥2 portions of onion per week, 0.69 (95% CI, 0.41-1.15) for high garlic intake, and 0.70 (95% CI, 0.39-1.28) for frequent use of both onion and garlic. Besides our study, 22 case-control and four cohort studies were included in the meta-analyses (>10000 cases). The pooled relative risks for the highest versus lowest intake category were 0.78 (95% CI, 0.67-0.91) for allium vegetables (ten case-control and four cohort studies), 0.60 (95% CI, 0.47-0.76) for garlic (12 case-control studies), and 0.55 (95% CI, 0.41-0.73) for onion (13 case-control studies). The pooled relative risk for high allium vegetable intake from the four cohorts was 1.02 (95% CI, 0.88-1.18). High allium vegetable consumption is likely to reduce gastric cancer risk. This evidence is derived mainly from case-control studies. Further data from large cohorts are desirable for conclusive confirmation.

Risk of neuroblastoma, maternal characteristics and perinatal exposures: The SETIL study

PurposeNeuroblastoma (NB) is the most common extra-cranial paediatric solid tumour. Incidence peaks in infancy, suggesting a role of in-utero and neonatal exposures but its aetiology is largely unknown. The aim of the present study is to evaluate the association between maternal characteristics and perinatal factors with the risk of NB, using data from the SETIL database. MethodsSETIL is a large Italian population-based case-control study established to evaluate several potential cancer risk factors in 0–10 year olds. Information about maternal characteristics, reproductive history, environmental and occupational exposures during pregnancy, as well as newborns’ characteristics were obtained using a structured questionnaire. Extremely low frequency magnetic field (ELF-MF) home exposure was measured. The study included 1044 healthy controls and 153 NB cases, diagnosed between 1998 and 2001. ResultsA twofold risk was associated to exposure in pregnancy to chemical products for domestic work and to hair dye. The risk associated with the latter was higher among 0–17 month old children (OR=5.5, 95%CI: 1.0–29.3). Risk was increased for children whose mothers had suffered work related exposure in the preconception period to solvents (OR=2.0 95%CI: 1.0–4.1) and in particular to aromatic hydrocarbons (OR=9.2, 95%CI: 2.4–34.3). No association was observed with ELF-MF exposure. A higher risk was found among children with congenital malformations (OR=4.9, 95%CI: 1.8–13.6) or neurofibromatosis (2 cases and 0 controls, p=0.016). ConclusionsOur study suggests maternal exposure to hair dyes and aromatic hydrocarbons plays a role and deserves further investigation. The association with congenital malformations might also be explained by over-diagnosis.External exposure, in particular during and before pregnancy might contribute to NB occurrence.

Reproductive and hormonal factors, family history, and breast cancer according to the hormonal receptor status

The aim of this study was to investigate the association between breast cancer risk, reproductive factors, and family history of breast cancer by the estrogen receptor (ER) and progesterone receptor (PR) status. We analyzed data from an Italian case-control study including 1075 women with incident breast cancer and 1477 hospital controls. We estimated the odds ratios (ORs) of breast cancer using unconditional logistic regression models including major recognized risk factors for breast cancer. Stronger associations with ER+ than with ER- breast cancer were observed for parity (OR: 0.7 vs. 0.9 for ≥ 3 births vs. nulliparae), age at first birth (OR: 1.6 vs. 1.2 for age ≥ 30 vs. <25 years), menopausal status (OR: 0.7 vs. 0.8 for postmenopause vs. pre/perimenopause), age at menopause (OR: 1.3 vs. 1.2 for menopause at age ≥ 50 vs. <50 years), and family history of breast cancer (OR: 2.2 vs. 1.4). Among the ER+ patients, the presence of PR+ did not appreciably modify any of the risk estimates. The association with age at menarche and hormone replacement therapy use was neither significant nor heterogeneous across ER and PR subtypes. In conclusion, we found stronger associations with selected menstrual and reproductive factors for ER+ (PR+) than for ER- (PR-) breast cancers, though in the absence of significant heterogeneity.

Dietary glycemic index, glycemic load and risk of age-related cataract extraction: a case-control study in Italy.

Although a role of glycemic index (GI) and glycemic load (GL) in age-related cataract development is plausible, a few studies, all conducted in USA or Australia, provided results on this issue. The aim of the present study was to provide new original data from a Mediterranean population. We analyzed data from an Italian case-control study including 761 cases with cataract extraction and 1,522 hospital controls, frequency-matched with cases by center, sex, and age. Multivariate odds ratios (ORs) for GI and GL intakes were obtained from logistic regression models after allowance for major confounding factors, including non carbohydrate energy intake, smoking, and diabetes. The ORs of cataract extraction for the highest versus the lowest tertile were 1.20 (95% confidence interval, CI 0.91-1.57) for GI and 1.57 (95% CI 1.16-2.13) for GL, with a statistically significant trend in risk for GL (p < 0.01). Results were materially unchanged when diabetics were excluded from the analysis. No heterogeneity emerged across strata of sex, age, education, smoking habits and body mass index. The present study supports a positive association between dietary GL and the risk of cataract extraction, independently from diabetes, and a lack of association for GI.

0169 Sinonasal cancers: is intestinal type adenocarcinoma the only related to occupational exposures? Results from an Italian case-control study

ObjectivesEpithelial sinonasal cancers (SNC) are rare, severe diseases associated to the exposure to several well-established carcinogens (IARC). The etiologic role of these carcinogens in different histological subtypes is still disputed,...

Nutrient-based dietary patterns and prostate cancer risk: a case–control study from Italy

The role of various foods and nutrients, and their combinations, on prostate cancer risk remains largely undefined. We addressed therefore the issue of complex dietary patterns. We analyzed data from an Italian case-control study, including 1,294 men with prostate cancer and 1,451 hospital controls. We carried out an exploratory principal component factor analysis on 28 selected nutrients in order to identify dietary patterns. We estimated odds ratios (ORs) and corresponding confidence intervals (CIs) using logistic regression models on quintiles of factor scores, adjusting for major confounding variables. We identified five dietary patterns, labeled "Animal Products," "Vitamins and Fiber," "Starch-rich," "Vegetable Unsaturated Fatty Acids (VUFA)," and "Animal Unsaturated Fatty Acids (AUFA)." We found positive associations between prostate cancer and "Animal Products" (OR for the highest vs. the lowest score quintile: 1.51, 95 % CI 1.16-1.96), "Starch-rich" (OR 1.50, 95 % CI 1.16 1.93), and "AUFA" (OR 1.32, 95 % CI 1.02-1.70) patterns. No significant associations emerged with "Vitamins and Fiber" (OR 0.93) and "VUFA" (OR 1.16) patterns. Our findings suggest that a diet rich in animal products, including several types of meat and dairy products, as well as of (refined) cereals and sugars has an unfavorable role on prostate cancer.

A study of tumour growth based on stoichiometric principles: a continuous model and its discrete analogue

In this paper, we consider a continuous mathematically tractable model and its discrete analogue for the tumour growth. The model formulation is based on stoichiometric principles considering tumour-immune cell interactions in potassium (K +)-limited environment. Our both continuous and discrete models illustrate ‘cancer immunoediting’ as a dynamic process having all three phases namely elimination, equilibrium and escape. The stoichiometric principles introduced into the model allow us to study its dynamics with the variation in the total potassium in the surrounding of the tumour region. It is found that an increase in the total potassium may help the patient fight the disease for a longer period of time. This result seems to be in line with the protective role of the potassium against the risk of pancreatic cancer as has been reported by Bravi et al. [Dietary intake of selected micronutrients and risk of pancreatic cancer: An Italian case-control study, Ann. Oncol. 22 (2011), pp. 202–206].

Smoking and Body Mass Index and Survival in Pancreatic Cancer Patients

The objective of this study was to provide further information on the role of personal characteristics and lifestyle factors, including obesity, diabetes, and tobacco smoking, on survival from pancreatic cancer. We obtained follow-up data of pancreatic cancer patients enrolled in 2 Italian case-control studies. Information on characteristics and habits up to the time of diagnosis was collected by trained interviewers. Vital status was ascertained through population registers and record linkage with health system databases. Hazard ratios (HRs) of all-cause mortality and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. Follow-up information was retrieved for 648 cancer patients. Compared with subjects with body mass index of less than 25 kg/m, the HRs were 1.14 (95% CI, 0.94-1.39) for overweight (ie, 25-29.9 kg/m) and 1.32 (95% CI, 0.98-1.79) for obese (ie, ≥30 kg/m) patients (trend P = 0.046). The HRs were 1.37 (95% CI, 1.14-1.65) for ever, 1.30 (95% CI, 1.03-1.65) for ex-smokers, and 1.42 (95% CI, 1.16-1.73) for current versus never smokers. Increasing amount and duration of smoking were associated with reduced survival after pancreatic cancer. No association emerged with diabetes, alcohol consumption, and diet. Smoking and overweight before diagnosis may play a role in the prognosis of pancreatic cancer, besides its etiology.

Associations of bread and pasta with the risk of cancer of the breast and colorectum

BackgroundCarbohydrate foods with high glycemic and insulinemic potential may influence cancer risk possibly through the insulin/growth-factor axis. Two staple carbohydrate foods of the Mediterranean diet, bread and pasta, have different glycemic and insulinemic responses and hence may affect cancer risk differently. Materials and methodsWe studied the association of bread and pasta with breast and colorectal cancer risk using data from two Italian case–control studies. These studies included 2569 women with histologically confirmed breast cancer and 1953 men and women with colorectal cancer. Controls were 2588 and 4154, respectively, admitted to the same hospitals as cases for acute, non-neoplastic conditions. Multivariate odds ratios (ORs) were obtained after allowance for relevant confounding factors. ResultsThe ORs of breast cancer for the highest versus the lowest quintile were 1.28 (95% confidence interval, CI: 1.03–1.58, P-trend = 0.0342) for bread and 1.07 (95% CI: 0.88–1.31, P-trend = 0.7072) for pasta. The association with bread remained virtually unchanged with postmenopause and overweight. The ORs of colorectal cancer in women for the highest versus the lowest quintile were 2.02 (95% CI: 1.46–2.80, P-trend = 0.0002) for bread and 1.37 (95% CI: 1.00–1.88, P-trend = 0.0164) for pasta. The associations remained significant only for bread in strata of menopausal status and in women with overweight. No significant associations were seen in men for either bread or pasta. ConclusionsOverall, these two cancer case–control studies showed stronger positive associations with bread than pasta in women, particularly if overweight, suggesting possible hormonal-related mechanisms.

267 Occupation and Multiple Sclerosis: an Italian case-control study

ObjectivesThe aim of the study is to explore possible relationships between occupational exposures and Multiple Sclerosis (MS), whose etiology is not well defined yet. To date, only few literature data...

Proanthocyanidins and other flavonoids in relation to endometrial cancer risk: a case–control study in Italy

Background:Because of their antioxidant and antimutagenic properties, flavonoids may reduce cancer risk. Some flavonoids have antiestrogenic effects that can inhibit the growth and proliferation of endometrial cancer cells.Methods:In order to examine the relation between dietary flavonoids and endometrial cancer, we analysed data from an Italian case–control study including 454 incident, histologically confirmed endometrial cancers and 908 hospital-based controls. Information was collected through a validated food-frequency questionnaire. We applied data on food and beverage composition to estimate the intake of flavanols, flavanones, flavonols, anthocyanidins, flavones, isoflavones, and proanthocyanidins. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from multiple logistic regression models conditioned on age and study centre and adjusted for major confounding factors.Results:Women in the highest quartile category of proanthocyanidins with ⩾3 mers vs the first three quartile categories had an OR for endometrial cancer of 0.66 (95% CI=0.48–0.89). For no other class of flavonoids, a significant overall association was found. There was a suggestion of an inverse association for flavanones and isoflavones among women with body mass index <25 kg m−2, and, for flavanones, among parous or non-users of hormone-replacement therapy women.Conclusion:High consumption of selected proanthocyanidins may reduce endometrial cancer risk.

Aspartame, low-calorie sweeteners and disease: Regulatory safety and epidemiological issues

Aspartame is a synthetic sweetener that has been used safely in food for more than 30 years. Its safety has been evaluated by various regulatory agencies in accordance with procedures internationally recognized, and decisions have been revised and updated regularly. The present review summarizes the most relevant conclusions of epidemiological studies concerning the use of low-calorie sweeteners (mainly aspartame), published between January 1990 and November 2012. In the Nurses' Health study and the Health Professionals Followup study some excess risk of Hodgkin lymphoma and multiple myeloma was found in men but not in women; no association was found with leukemia. In the NIH-AARP Diet and Health Study, there was no association between aspartame and haematopoietic neoplasms. US case-control studies of brain and haematopoietic neoplasms also showed no association. The NIH-AARP Diet and Health Study and case-control studies from California showed no association with pancreatic cancer, and a case-control study from Denmark found no relation with breast cancer risk. Italian case-control studies conducted in 1991-2008 reported no consistent association for cancers of the upper aerodigestive tract, digestive tract, breast, endometrium, ovary, prostate, and kidney. Low calorie sweeteners were not consistently related to vascular events and preterm deliveries.

Dietary total antioxidant capacity and colorectal cancer: A large case-control study in Italy

A favorable role of fruit and vegetables on colorectal cancer risk has been related to the antioxidant properties of their components. We used data from an Italian case-control study including 1,953 patients with incident, histologically confirmed colorectal cancer (1,225 colon and 728 rectal cancers). Controls were 4,154 patients admitted to hospital for acute, non-neoplastic conditions. A reproducible and valid food frequency questionnaire was used to assess subjects' usual diet. Total antioxidant capacity (TAC) was measured using Italian food composition tables in terms of ferric reducing-antioxidant power (FRAP), Trolox equivalent antioxidant capacity (TEAC) and total radical-trapping antioxidant parameter (TRAP). We estimated the odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) through multiple logistic regression models, including terms for potential confounding factors, and energy intake. TAC was inversely related with colorectal cancer risk: the OR for the highest versus the lowest quintile was 0.68 (95% CI, 0.57-0.82) for FRAP, 0.69 (95% CI, 0.57-0.83) for TEAC and 0.69 (95% CI, 0.57-0.83) for TRAP. Corresponding values, excluding TAC deriving from coffee, were 0.75 (95% CI, 0.61-0.93) for FRAP, 0.76 (95% CI, 0.61-0.93) for TEAC and 0.71 (95% CI, 0.57-0.89) for TRAP. The inverse association was apparently-though not significantly-stronger for rectal than for colon cancer. This is the first case-control study indicating consistent inverse relations between dietary TAC and colorectal cancer risk.

Erratum to “Increased lung cancer risk among bricklayers in an italian population-based case-control study”

Erratum to “Increased lung cancer risk among bricklayers in an italian population-based case-control study”

Nutrient-based dietary patterns and pancreatic cancer risk

PurposeFew data are available on the role of combinations of foods and/or nutrients on pancreatic cancer risk. To add further information on dietary patterns potentially associated to pancreatic cancer, we applied an exploratory principal component factor analysis on 28 major nutrients derived from an Italian case-control study. MethodsCases were 326 incident pancreatic cancer cases and controls 652 frequency-matched controls admitted to hospital for non-neoplastic diseases. Dietary information was collected through a validated and reproducible food frequency questionnaire. Multiple logistic regression models adjusted for sociodemographic variables and major recognized risk factors for pancreatic cancer were used to estimate the odds ratios (OR) of pancreatic cancer for each dietary pattern. ResultsWe identified four dietary patterns—named “animal products,” “unsaturated fats,” “vitamins and fiber,” and “starch rich,” that explain 75% of the total variance in nutrient intake in this population. After allowing for all the four patterns, positive associations were found for the animal products and the starch rich patterns, the OR for the highest versus the lowest quartiles being 2.03 (95% confidence interval [CI], 1.29–3.19) and 1.69 (95% CI, 1.02–2.79), respectively; an inverse association emerged for the vitamins and fiber pattern (OR, 0.55; 95% CI, 0.35–0.86), whereas no association was observed for the unsaturated fats pattern (OR, 1.13; 95% CI, 0.71–1.78). ConclusionsA diet characterized by a high consumption of meat and other animal products, as well as of (refined) cereals and sugars, is positively associated with pancreatic cancer risk, whereas a diet rich in fruit and vegetables is inversely associated.