Publications

The relationship between alcohol drinking (mainly wine) and risk of colon and rectal cancer was considered in a case-control study conducted between 1991 and 1996 in six Italian centers. Cases were 1,225 patients < 75 years of age with histologically confirmed cancer of the colon and 728 patients with cancer of the rectum; controls were 4,154 patients admitted to hospital for a wide spectrum of acute, nonneoplastic diseases. Compared with never drinkers, the odds ratios (OR) for current drinkers in the higher quintile of total alcohol intake (> 51.82 g ethanol/day) were 1.01 for colon cancer and 0.90 for rectal cancer, and those for ex-drinkers were 1.20 and 1.07, respectively. The OR for wine drinkers in the highest quartile of intake were 1.07 for colon cancer and 0.97 for rectal cancer. No association was found with duration of the habit, time since starting, or age at starting. Among ex-drinkers, no association appeared with time since stopping. No significant heterogeneity was found across strata of age at diagnosis, sex, education, smoking status, physical activity, family history of colorectal cancer, beta-carotene, vitamin C, coffee, total fiber and folate intake, and number of meals per day. No significant association appeared for various intestinal subsites.

We studied the determinants of low bone mineral density, using data from a population-based screening program of osteoporosis carried out among 1,373 women (age 40-64 years) in the province of Pordenone, Italy, by means of dual photon absorptiometry of the lumbar spine. Menopause had a major effect on bone mineral density. Age had little influence before menopause. In multivariate linear regression analyses, weight was the strongest predictor of bone mineral density in pre- as well as postmenopausal women. After the inclusion in a single model of a term for current weight, weight at ages 12 and 30 years explained some additional variance, whereas high waist-to-hip ratio (an indicator of central adiposity) had no influence. Smoking 15 or more cigarettes per day entailed a small increased risk of osteoporosis, but this effect, independent of weight, appeared to be restricted to premenopausal women. No food or micronutrient that we examined was predictive of bone mineral density, nor was coffee or alcoholic beverage intake.

Alcohol and tobacco consumption are well-recognized risk factors for head and neck cancer (HNC). Evidence suggests that genetic predisposition may also play a role. Only a few epidemiologic studies, however, have considered the relation between HNC risk and family history of HNC and other cancers. We pooled individual-level data across 12 case-control studies including 8,967 HNC cases and 13,627 controls. We obtained pooled odds ratios (OR) using fixed and random effect models and adjusting for potential confounding factors. All statistical tests were two-sided. A family history of HNC in first-degree relatives increased the risk of HNC (OR=1.7, 95% confidence interval, CI, 1.2-2.3). The risk was higher when the affected relative was a sibling (OR=2.2, 95% CI 1.6-3.1) rather than a parent (OR=1.5, 95% CI 1.1-1.8) and for more distal HNC anatomic sites (hypopharynx and larynx). The risk was also higher, or limited to, in subjects exposed to tobacco. The OR rose to 7.2 (95% CI 5.5-9.5) among subjects with family history, who were alcohol and tobacco users. A weak but significant association (OR=1.1, 95% CI 1.0-1.2) emerged for family history of other tobacco-related neoplasms, particularly with laryngeal cancer (OR=1.3, 95% CI 1.1-1.5). No association was observed for family history of nontobacco-related neoplasms and the risk of HNC (OR=1.0, 95% CI 0.9-1.1). Familial factors play a role in the etiology of HNC. In both subjects with and without family history of HNC, avoidance of tobacco and alcohol exposure may be the best way to avoid HNC.

In a comprehensive study of the Swedish Family Cancer Database (including 10.2 million individuals, with 190,000 mothers' and 26,000 daughters' breast cancers), Hemminki et al.1 estimated a population-attributable fraction (PAF) of 7.05% of all breast cancers (3.6% for mother history, 3.0% for sister, 0.4% for both). These figures represent a reference standard for familiar breast cancer, given the unbiased design of the study and its uniquely large dataset. Using data from a hospital-based case-control study of 2,569 incident, histologically confirmed breast cancer cases and 2,588 controls from 6 Italian geographic areas,2, 3 including information on family history of breast cancer in first-degree relatives and age at occurrence of each neoplasm, we estimated an overall odds ratio (OR) for familial history of 2.4, corresponding to an overall PAF of approximately 7%. Table I gives more detailed analyses of the same dataset in strata of age and history of mother, sister and other/more than one relative with history of breast cancer. Multivariate ORs of breast cancer were derived from unconditional multiple logistic regression models, including terms for age, study center, education, age at first birth and age at menopause. A term for number of sisters was also included to obtain ORs and PAFs for breast cancer history in sisters, which is a function of number of sisters. Using the distribution of risk factors in the cases and the ORs from the models, PAFs were computed for various combinations of family history and age, using the method described by Bruzzi et al.4 This implies knowledge of the risk estimates and of the distribution of the risk factors of interest in the population of cases only and can therefore be applied to data of hospital-based case-control studies. PAFs were expressed as percent terms, together with the corresponding 95% CI.5 The PAF at all ages was 2.86% for mothers' history, 3.15% for sisters' and 1.11% for other/combined. As in the Swedish dataset, the PAF tended to decline with increasing probands' age at diagnosis for maternal history from 4.01 at age <45 to 1.25 at age ≥60, but to increase with sister history from 1.10 at age <45 to 5.74 at age ≥60, reflecting the low proportion of sisters with breast cancer in younger women. The overall multivariate PAF for any familial breast cancer was 7.12% (8.62% below age 45). In epidemiology, replication of findings using different methodologic approaches is a key factor for any quantitative inference. The strict consistency of the PAF estimates from a population-based record-linkage study and a hospital-based case-control study gives reassuring evidence of the reliability and validity of information on family history of breast cancer collected through interviews.6 Yours sincerely, The authors thank Ivana Garimoldi for editorial assistance. Claudio Pelucchi*, Eva Negri*, Alessandra Tavani*, Silvia Franceschi , Carlo La Vecchia* , * Istituto di Ricerche Farmacologiche “Mario Negri”, Milano, Italy, Field and Intervention Studies Unit, International Agency for Research on Cancer, Lyon Cedex, France, Istituto di Statistica Medica e Biometria, Università degli Studi di Milano, Milano, Italy.

Epidemiological and toxicological evidence suggests that PFOA and PFOS elicit a decrease in BrthW both in humans and rodents. However, the effective animal extrapolated serum concentrations are 10²-10³ times higher than those in humans. Thus, there is no quantitative toxicological evidence to support the epidemiological association, thus reducing the biological plausibility of a causal relationship.

Inflammation and immunity are linked to intestinal adenoma (IA) and colorectal cancer (CRC) development. The gut microbiota is associated with CRC risk. Epithelial barrier dysfunction can occur, possibly leading to increased intestinal permeability in CRC patients. We conducted a case-control study including 100 incident histologically confirmed CRC cases, and 100 IA and 100 healthy subjects, matched to cases by center, sex and age. We performed 16S rRNA gene analysis of blood and applied conditional logistic regression. Further analyses were based on negative binomial distribution normalization and Random Forest algorithm. We found an overrepresentation of blood 16S rRNA gene copies in colon cancer as compared to tumor-free controls. For high levels of gene copies, community diversity was higher in colon cancer cases than controls. Bacterial taxa and operational taxonomic unit abundances were different between groups and were able to predict CRC with an accuracy of 0.70. Our data support the hypothesis of a higher passage of bacteria from gastrointestinal tract to bloodstream in colon cancer. This result can be applied on non-invasive diagnostic tests for colon cancer control.