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Pathological correlates of potential autoimmune gastritis (AIG), defined by anti-parietal cell antibody (PCA) positivity in the absence of gastric atrophy, have never been described. We herein aimed to assess intraepithelial lymphocyte (IEL) infiltration in gastric corpus of AIG patients. From 2000 to 2021, among 53 potential AIG patients, we focused on nine (median age 61 years, IQR 53-82; four females) who subsequently developed overt AIG. IEL infiltration of the oxyntic mucosa was assessed before and after developing overt AIG by measuring deep and superficial CD3+ IEL. AIG patients with different degrees of corpus atrophy, healthy controls (HC), active H. pylori gastritis, celiac disease (CD), and Hashimoto’s thyroiditis patients were included as controls. Of note, deep, but not superficial, CD3+ IEL count was higher (p7/100 epithelial cells allowed discrimination of any AIG stage and severity (AUC=0.842). We conclude that an increased deep CD3+ IEL infiltration of the oxyntic mucosa could represent a marker of potential AIG. Prospective studies including a larger number of potential AIG patients are needed.

Recent studies support the hypothesis that microbes can seed some Alzheimer’s disease (AD) cases, leading to inflammation and overproduction of amyloid peptides. Porphyromonas gingivalis (Pg) is a keystone pathogen of chronic periodontitis and has been identified as risk factor for the development and progression of AD. The present preliminary study aimed to quantify Pg abundance in neurodegenerative disease (ND) patients compared with neurologic patients without neurodegenerative disorders (no-ND) and healthy controls (HC) to determine possible association between Pg abundance and neurodegenerative process. Pg was quantified on DNA extracted from the oral samples of 49 patients and 29 HC by quantitative polymerase chain reaction (qPCR). Anti-Pg antibodies were also detected on patient serum samples by enzyme-linked immunosorbent assays (ELISA). The Pg abundance in the oral cavity was significantly different among groups (p = 0.004). It was higher in ND than no-ND (p = 0.010) and HC (p = 0.008). The Pg abundance was correlated with the antibodies (p = 0.001) with different slopes between ND and no-ND (p = 0.037). Pg abundance was not correlated with oral indices and comorbidities. These results extend our understanding of the association between oral pathogens and AD to other neurodegenerative processes, confirming the hypothesis that oral pathogens can induce an antibody systemic response, influencing the progression of the disease.

BACKGROUND Autoimmune atrophic gastritis (AAG) is an immune-mediated disorder characterised by destruction of gastric oxyntic mucosa AIM: To explore gastric histopathological evolution in a cohort of AAG patients over a prolonged follow-up METHODS: Single centre prospective study enrolling consecutive patients with histologically confirmed AAG between 2000 and 2018. All AAG patients undergoing endoscopic follow-up every 1-3 years were classified as having stages 1, 2 or 3 according to atrophy severity (mild, moderate and severe). AAG patients with either glandular or neuroendocrine dysplasia/neoplasia were classified as having stage 4. Disease stage progression, and changes in serum anti-parietal cell antibody (PCA), chromogranin A and gastrin-17 were assessed. RESULTS In total, 282 AAG patients (mean age 60.3 years; F:M ratio 2.4:1; median follow-up 3 years, interquartile range 1-7) were enrolled. All patients with stages 1 or 2 progressed to stage 2 or 3 over time with a steady trend (P = .243) and regression from a severe to a milder stage was never noticed. Disease progression of patients with stages 1 or 2 occurred within the first 3 years. PCA positivity rate did not change over time. Stage 3 patients had higher gastrin-17 levels compared to patients with stages 1 and 2 (median 606 vs 295 pg/mL; P

Ribatti D, Marzullo A, Gentile A, Longo V, Nico B, Vacca A & Dammacco F (2007) Histopathology 50, 591–596 Erythropoietin/erythropoietin-receptor system is involved in angiogenesis in human hepatocellular carcinoma Aims To correlate microvascular density and erythropoietin (Epo)/Epo-receptor (EpoR) expression in endothelial and tumour cells with histopathological type in hepatocellular carcinoma (HCC). Methods and results Specimens of primary HCC obtained from 50 patients who had undergone curative hepatectomy were investigated immunohistochemically by using anti-CD31, anti-Epo and anti-EpoR antibodies. Poorly differentiated HCC had a higher degree of vascularization than other stages and Epo/EpoR expression in both tumour and endothelial cells increased in parallel with grade of malignancy and was highly correlated with the extent of angiogenesis. Conclusions Epo/EpoR levels correlate with angiogenesis and progression of patients with HCC and these findings suggest the presence of a loop in the Epo/EpoR system, i.e. Epo is secreted by hepatic tumour cells and it affects vascular endothelial cells via its receptors and promotes angiogenesis in a paracrine manner. It is thus suggested that Epo is an important factor in hepatic tumour angiogenesis. Understanding the mechanisms of HCC angiogenesis provides a basis for a rational approach to the development of antiangiogenic therapy in patients with hepatic cancer.

The relationship between the consumption of salt and the risk of gastrointestinal cancer was examined using data from a case-control study conducted in northern Italy. The study was conducted on 526 incident cases of gastric cancer, 621 of colon cancers, 382 of rectal cancers, and 1,223 controls admitted to hospital for acute, nonneoplastic, nondigestive tract disorders. Compared with those for people with low salt intakes, the relative risks (and 95% confidence intervals) for those with intermediate and high salt intakes were 1.3 (1.0-1.8) and 1.2 (0.8-1.7) for stomach, 1.0 (0.8-1.3) and 1.1 (0.8-1.5) for colon, and 1.2 (0.9-1.6) and 0.9 (0.6-1.3) for rectum. None of the trends in risk were statistically significant, and the risk estimates were not materially modified by allowance for major identified potential confounding factors. Thus, this study gives little support to the existence of any strong association between salt intake and gastrointestinal cancers. However, in view of the results obtained and of the uncertainties of salt intake measurement, the possibility exists of a real, although moderate, association of salt intake with gastric cancer.

STUDY OBJECTIVE--The aim was to investigate the relationship between oral contraceptives, non-contraceptive oestrogens, and the risk of gallstone disease requiring surgery. DESIGN--This was a hospital based case-control study carried out between 1987 and 1990. Main outcome measures were frequency of consumption of oral contraceptives and non-contraceptive oestrogens, and the corresponding multivariate relative risk estimates and 95% confidence intervals (CI) in relation to various measures of use of the preparations. SETTING--A network including major teaching and general hospitals in the greater Milan area, northern Italy. SUBJECTS--Subjects were 235 women with gallstones requiring surgery and 538 controls admitted for acute diseases, other than digestive or hormonal diseases or those potentially influencing the use of female hormone preparations. MAIN RESULTS--For oral contraceptives, the relative risk for ever use was 0.8 with 95% CI 0.4 to 1.5. With reference to duration of use, the multivariate relative risk was 1.0 for less than two and 0.5 for two or more years of use. The relative risk was 1.7 (95% CI 0.6 to 4.7) in women who had last used the pill less than five years before diagnosis, but declined to 0.4 (95% CI 0.2 to 1.0) in those who had stopped more than five years before. With reference to oestrogen replacement treatment, the relative risk for ever use was 1.9 (95% CI 1.0 to 3.1). The relative risk, however, was not related to duration of use, since it was 1.8 for less than two and 1.5 for two or more years of use. Relative risk was higher for women who had last used non-contraceptive oestrogens 10 or more years before diagnosis (2.4) than for shorter periods since last use (1.3). CONCLUSIONS--On a clinical and public health scale, oral contraceptives and non-contraceptive oestrogens are unlikely to have an important influence in the aetiology of gallbladder disease.

The relation between selected anthropometric indicators and the risk of endometrial cancer was evaluated using data from a case-control study conducted in Northern Italy on 562 cases and 1780 controls in hospital for acute, non-neoplastic or hormone-related disease. There was no appreciable association between height and endometrial cancer: compared with the lowest quintile, the multivariate relative risks (RR) were 0.9, 0.9, 0.7 and 0.8 for each subsequent quintile. Weight was directly associated with risk (RR = 2.7 for top vs. bottom quintile), and the positive association was even stronger when indices of body mass which make allowance for height were considered: the relative risks for extreme quintiles were 3.4 for W/H2 (Quetelet's index, weight and height), 3.8 for W/H1.5 and 3.5 for W0.33/H. Surface area, which was positively correlated both with height and weight, showed a weaker direct association (RR = 2.4 between extreme quintiles). The relations with measures of body weight were apparently stronger in postmenopause, but the point estimates for the upper quintile were also around 2 in premenopausal women. Although the major findings of this study are not new, they provide more detailed information that was hitherto available on the relation between various anthropometric indicators and endometrial cancer risk. In relation to height, with the sample size of this study it was possible to exclude, at the conventional 95% probability, relative risks above 1.0 for the fourth and above 1.1 for the fifth as compared with the lowest quintile. This provides indirect evidence against the hypothesis that nutritional status early in life is related to the subsequent development of endometrial cancer.

STUDY OBJECTIVE--To examine the relation between selected foods and acute myocardial infarction in women. DESIGN--Case-control study conducted over five years. SETTING--30 Hospitals with coronary care units in northern Italy. SUBJECTS--287 Women who had had an acute myocardial infarction (median age 49, range 22-69 years) and 649 controls with acute disorders unrelated to ischaemic heart disease (median age 50, range 21-69 years) admitted to hospital during 1983-9. MAIN OUTCOME MEASURES--Frequency of consumption of various foods and odds ratios of risks associated with these foods. RESULTS--The risk of acute myocardial infarction was directly associated with frequency of consumption of meat (odds ratio 1.5 for upper v lower thirds of consumption), ham and salami (1.4), butter (2.3), total fat added to food (1.6), and coffee (2.8). Significant inverse relations were observed for fish (0.6), carrots (0.4), green vegetables (0.6), and fresh fruit (0.4). The risk was below one for moderate alcohol consumption (0.7) and above one for heavier intake (1.2). Allowance for major non-dietary covariates, including years of education, smoking, hyperlipidaemia, diabetes, hypertension, and body mass index, did not appreciably alter the estimates of risk for most of the foods; for coffee, however, the odds ratio fell to 1.8 on account of its high correlation with smoking. CONCLUSIONS--The frequency of consumption of a few simple foods may provide useful indicators of the risk of myocardial infarction. Furthermore, specific foods such as fish, alcohol, or vegetables and fruits may have an independent protective role in the risk of cardiovascular diseases.

The relationship between self-reported height and cancer risk was investigated in an integrated series of case-control studies including 273 cases of cancer of the oesophagus, 474 of the stomach, 558 of the colon, 352 of the rectum, 227 of the liver, 267 of the pancreas, 110 of the larynx, 2,388 of the breast, 545 of the cervix uteri, 563 of the endometrium, 688 of the ovary, 80 of the prostate, 263 of the bladder, 105 of the kidney, 43 Hodgkin's disease, 152 non-Hodgkin's lymphomas, 109 multiple myelomas, and a total of 5,574 controls admitted to hospital for acute, non-neoplastic conditions. No significant positive trend in risk was observed for any of the cancer sites considered, and some suggestion of elevated risks for the upper quintile of height was observed only for prostate (relative risk, RR = 1.4), kidney (RR = 2.7) and colon (RR = 1.2) in males (but not in females). For breast cancer, all the RRs for subsequent quintiles of height were close to unity. Four neoplasms showed significant inverse trends with height: oesophagus (RR = 0.7 for highest vs. lowest quintile), cervix (RR = 0.4), endometrium (RR = 0.7) and ovary (RR = 0.6). For oesophagus and cervix the trends could be explained, at least in part, in terms of social class correlates (multivariate RR 0.8 and 0.5, respectively), while for endometrium they could possibly be related to an inverse correlation between height and body mass (multivariate RR 0.9). Thus, our study did not support the hypothesis that nutrition in childhood and adolescence (which in this population is a determinant of adult height) is directly related to the subsequent risk of cancer at several major cancer sites. A number of inverse associations emerged, which may be either spurious and incidental, or suggest that poorer nutrition early in life may be an unfavourable indicator of the subsequent risk of selected neoplasms.

The relationship between use of non-contraceptive oestrogens and risk of breast cancer was investigated using data from a hospital-based case-control study from Northern Italy. This study covered 1,108 patients with histologically confirmed breast cancers and 1,281 control subjects with a large spectrum of acute conditions unrelated to any of the known or suspected risk factors for breast cancer. Compared with "never-users", the age-adjusted relative risk for "ever-users" was 1.93 (95% confidence interval = 1.35-2.75). The risk increased with duration of use (relative risk = 2.08 for over 2 years), but was unrelated to time elapsed since first or last use. Allowance for a large number of identified potential confounding factors, including indicators of socio-economic status and the major determinants of breast cancer risk, failed to account for the observed association (multivariate relative risk = 1.84 for ever use and 2.04 for greater than 2 year use). Possible explanations for these findings and for their apparent discrepancy with some American data are discussed in terms of different baseline incidence of breast cancer in the two populations, and hence of potential baseline differences in availability of endogenous serum oestrogens. Nonetheless, the results of this study should be interpreted cautiously and viewed as a further contribution to a topic still open to debate.

We evaluated the risk of breast cancer in relation to the frequency of consumption of a few selected dietary items. Data were used from a case-control study of 1,108 histologically confirmed breast cancer patients and 1,281 control subjects who were in the hospital for acute conditions unrelated to any of the established or suspected risk factors for breast cancer. Moderately elevated risk estimates were associated with higher levels of fat consumption in seasonings [butter, margarine, and oil, relative risk (RR) = 1.34, 95% confidence interval (CI) = 1.06-1.71] and meat (RR = 1.36, 95% CI = 1.12-1.65), whereas a reduced risk (RR = 0.42, 95% CI = 0.34-0.51) was associated with a more frequent green vegetable consumption. It was not possible to show that these associations were incidental, because allowance for several identified potential confounding factors, including the major identified or potential risk factors for breast cancer, did not materially modify the risk estimates. Further, no appreciable interaction emerged with age or menopausal status, because the diet-related risk estimates were similar in pre- or postmenopausal women. However, the implications of these findings in terms of specific micronutrients (e.g., retinol or beta-carotene) and biological correlates are still unclear. Alcohol consumption was significantly greater among breast cancer cases, with a multivariate risk estimate of 2.92 for the highest level. Thus, the present findings confirm that various aspects of diet may influence the risk of breast cancer, although the small amount of available knowledge does introduce serious uncertainties in any discussion of the potential implications in terms of prevention on a public health scale.

The risk of breast cancer in relation to use of oral contraceptives was evaluated using data from a hospital-based case-control study from Northern Italy on 1517 cases below age 60 and 1351 controls admitted for acute diseases unrelated to any of the known or potential risk factors for breast cancer. The multivariate relative risk for ever vs. never users was 1.3 (95% confidence interval = 1.0-1.7). However, the risk was not related to duration of use: indeed the highest risk was observed among short-term users (less than 2 years), and the point estimate was 0.9 among users for 5 years or more. The elevated risk among short-term users, if not due to residual confounding or selection mechanisms, is probably explainable in terms of recall bias (i.e. more careful report of short or very short use by cases). No definite pattern was observed in relation to latency or recency of use, and the point estimates were 0.8 for women who had ever used the pill before age 25 and 0.8 for those who had ever used the pill before first full-term pregnancy. Thus, the study presents further reassuring information on the oral contraceptive/breast cancer debate. Its major limitation lies in the low prevalence of oral contraceptive users in Italy, with a consequently reduced statistical power, although, with the number of cases involved, it was possible to exclude a relative risk of 1.4 for long-term use or for ever use before first birth.

The risk of invasive and intraepithelial cervical neoplasia in relation to the frequency of intake of the major sources of preformed vitamin A (retinol) and β-carotene in the Italian diet was analyzed in a study of 392 cases of invasive cancer compared with 392 age-matched controls hospitalized for acute conditions unrelated to any of the established or suspected risk factors for cervical cancer, and of 247 cases of cervical intraepithelial neoplasia compared with 247 controls found to have normal smears at the same screening clinics where cases had been identified. Women with invasive cancer consumed milk, green vegetables, and carrots less frequently, but no significant relation was noted for meat or liver. Consequently, estimated β-carotene, but not retinol, intake was inversely and strongly related to the risk of invasive cervical cancer. Compared with women whose intake was over 150,000 international units (IU) per month, the relative risks were 3.0 for 100 to 149,999 and 4.7 for less than 100,000 IU. It was not possible to show that these relationships were incidental, since allowance for several identified potential distorting factors, including indicators of social status and the major risk factors for cervical cancer, did not materially modify the risk estimates. In contrast, no association emerged between any of the food items and vitamin A estimates considered and intraepithelial neoplasia. Thus, the results of this study can be interpreted in one of two ways: either some residual uncontrolled bias was responsible for the strong dietary correlates of invasive cervical cancer risk or β-carotene (or any other correlate of a vegetable-rich diet) has effect on one of the later stages of the process of carcinogenesis, thus influencing the risk of invasive carcinoma but not of its precursors.

The relation between ovarian cancer and coffee drinking habits was evaluated in a case-control study of 247 histologically confirmed epithelial ovarian cancers and 494 age-matched controls, admitted to hospital for acute conditions apparently unrelated to coffee consumption. Compared to rates for women who had never drunk coffee, the crude relative risk estimates for those who drank less than two, two or three, and four or more cups per day were 1.3, 1.5 and 1.4 respectively; however, when allowance was made for smoking habits, these risk estimates became 1.3, 1.7 and 1.8 respectively, and a significant linear trend of increasing risk with more elevated coffee consumption was evident. These results were not explained by various other potential confounding factors, including the major risk factors for ovarian cancer, but we had no information on dietary variables. The relative risk, however, did not increase with increasing duration of use. The findings of this study give apparent support in favour of the hypothesis that coffee consumption, or related dietary variables, may be associated with the risk of epithelial ovarian cancer. Further studies in different settings, however, are required in order to establish whether this association is real, and if so, whether it is causal.

The relationship between menstrual factors and the risk of ovarian cancer was evaluated in the framework of a hospital-based case-control study conducted in the greater Milan area on a total of 634 cases of ovarian cancer and 1626 control subjects with a spectrum of acute conditions unrelated to any of the established or potential risk factors for ovarian cancer. Compared with women whose menarche occurred at age 13 or later, the risk of ovarian cancer was moderately (and not significantly) elevated for earlier menarche (multivariate relative risk, RR = 1.13, 95% confidence interval, CI = 0.97–1.37). There was a positive association with age at menopause, the multivariate relative risk, compared with women aged 45 years or less at menopause, being 1.25 for those aged 45–49 years, 1.40 for 50–53 and 1.58 for 54 or over (gc12 trend = 8.86, p = 0.003). A lifelong irregular menstrual pattern (defined as frequent menstrual-like episodes of bleeding less than 21 or more than 35 days apart) was negatively associated with the risk of ovarian cancer (multivariate RR = 0.45, 95% CI = 0.31–0.65). The effect of age at menopause and lifelong menstrual pattern was similar in different strata of age, whereas there was a positive association with early menarche among younger women which disappeared with advancing age. The present findings confirm the influence of various menstrual factors on the risk of epithelial ovarian cancer. In particular, since it has been suggested that “irregular” menstrual cycles are frequently anovulatory, some support is provided to the theory that ovarian carcinogenesis is affected at a higher rate during “normal” ovulatory cycles than during anovulatory periods.

The relation between dietary factors and the risk of colo-rectal cancer was investigated in a case-control study conducted in Northern Italy on 339 cases of colon cancer, 236 cases of rectal cancer and 778 controls admitted to hospital for acute, non-neoplastic or digestive disorders. Consistent positive associations were observed with more frequent consumption of starchy foods (pasta or rice) (relative risk, RR = 3.0 for colon and I.S for rectum (or highest vs. lowest fertile) and beef/veal meats (RR = 2.1 for colon, 2.1 for rectum), whereas reduced relative risks were observed in subjects reporting more frequent green vegetable consumption (RR = 0.5 for highest vs. lowest tertile), a few specific vegetable or fruit items, and coffee (RR = 0.6 for highest vs. lowest tertile). Various fats in seasonings were positively, but inconsistently, related to intestinal cancer risk, whereas no association was evident with measures of whole grain foods or alcohol intake. For both intestinal sites, a 4- to 5-fold difference in risk was evident between the extreme quintiles of a simple score obtained by algebraic sum of the A major groups of foods. These findings could not be explained in terms of confounding by socio-economic status or other major potential distorting factors, are in agreement with the results from previous studies of colo-rectal cancer in Southern Europe, and are consistent with various aspects of the descriptive epidemiology of intestinal cancer in Italy.

STUDY OBJECTIVE: To examine the relationship between smoking and myocardial infarction in women. DESIGN: Case-control study over 5 years. SETTING: Cases were women admitted to 30 coronary care units in northern Italy. Controls were admitted to the same hospitals with other acute disorders. PARTICIPANTS: These were 262 young and middle aged women with acute myocardial infarction (median age 49 years, range 24-69) and 519 controls with other acute disorders unrelated to ischaemic heart disease (median age 47 years, range 22-69). MEASUREMENTS AND MAIN RESULTS: Stratification and the Mantel-Haenszel procedure, and unconditional multiple logistic regression were used to obtain relative risks according to levels of cigarette smoking. The regression equations included terms for age, education, coffee and alcohol consumption, diabetes, hypertension, hyperlipidaemia, body mass index and oral contraceptive use. Compared to life long non-smokers, relative risk was not significantly above unity for ex-smokers but among current smokers showed a significant trend to increasing risk with larger numbers of cigarettes smoked, with risk estimates of 2.3, 5.9 and 11.0 for less than 15, 15-24 and greater than or equal to 25 cigarettes per day respectively. Smoking related risks were consistently raised across strata of hyperlipidaemia, hypertension and increased alcohol and coffee intake. CONCLUSIONS: In terms of population attributable risk, about 48% of all myocardial infarctions in young and middle aged Italian women were attributable to cigarette smoking, which is therefore by far the most important preventable determinant of the disease.

The analysis of alcohol and breast cancer risk from an Italian case-control study of breast cancer has been updated to include a total of 2402 women with histologically confirmed breast cancer and 2220 controls with acute conditions unrelated to any of the established or potential risk factors for breast cancer, admitted to a network of teaching and general hospitals in the greater Milan area. Compared with non-drinkers, the estimated relative risk for ever drinkers was 1.4 (95% CI = 1.2-1.6). The multivariate risks were 1.3 for less than 1 drink (e.g. 10 g of ethanol) per day, 1.3 for 1 less than 2 drinks, 1.4 for 2-3 and 2.2 for over 3 drinks per day. The positive association between alcohol and breast cancer was consistent across strata of age, socio-demographic variables, smoking, menstrual, reproductive, and hormonal factors, family history of breast cancer, nutrition and diet indicators. In particular, this study indicated that the alcohol-breast cancer relationship is probably not materially different in younger and older women, that alcohol drinking at an early age is not a particularly clear indicator of subsequent risk, nor that the effect of alcohol is enhanced in thin women. Thus, the findings of this study are both internally consistent and in agreement with most previous evidence, since the relative risks of 1.3-1.4 for a consumption of 10-30 g of alcohol per day compare well with the corresponding highest intake levels in most American studies. This study is of particular interest, since it provides data on higher levels of alcohol consumption, on which very little information is available. There are nontheless at least three elements which leave open the question of causality: the absence of duration-risk relationship, the inconsistency with evidence from descriptive epidemiology, and the lack of plausible biological mechanisms.

Socio-demographic characteristics, general lifestyle habits, reproductive and medical histories were compared of 328 women who had ever used oral contraceptives and 2306 never users from a case-control surveillance conducted in Northern Italy. Oral contraceptive use was positively and strongly related with the level of education and indicators of social class. The rate ratio of ever use (adjusted for age and diagnostic category) was 3.3 for women with 12 years of education or more compared with less than 7 years, and 3.0 for women of highest compared with lowest social class. The frequency of pill use was lower among never married women, and significantly elevated among smokers (rate ratio = 2.4 for heavy smokers). In contrast, no relation was evident between alcohol or coffee consumption and pill use. Likewise, ever users of oral contraceptives were not significantly different from women who had never used the pill with regard to major reproductive factors (parity and age at first pregnancy) or several medical variables of potential interest (e.g., diabetes, hypertension, hyperlipidemia), with the only possible exclusion of obesity which was less frequent among pill users. Thus, this study indicates that the major determinants of the persistently low frequency of oral contraceptive use in this Northern Italian population are social rather than reproductive or medical factors. These findings have important implications for epidemiological research on oral contraceptive and disease in this population, and underline the importance of selection and screening of oral contraceptive users on the basis of knowledge of medical factors and lifestyle habits.Socio-demographic characteristics, general lifestyle habits, and reproductive and medical histories were compared of 328 women who had ever used oral contraceptives (OCs) and 2306 never users from a case-control surveillance conducted in Northern Italy. OC use was positively and strongly related with the level of education and indicators of social class. The rate ratio of ever use (adjusted for age and diagnostic category) was 3.3 for women with 12 years of education or more compared with less than 7 years, and 3.0 for women of highest compared with lowest social class. The frequency of pill use was lower among never married women, and significantly elevated among smokers. In contrast, no relation was evident between alcohol or coffee consumption and pill use. Likewise, ever users of OCs were not significantly different from women who had never used the pill with regard to major reproductive factors (parity and age at 1st pregnancy) or several medical variables of potential interest (e.g., diabetes, hypertension, hyperlipidemia), with the only possible exclusion of obesity which was less frequent among pill users. Thus, this study indicates that the major determinants of the persistently low frequency of OC use in the Northern Italian population are social rather than reproductive or medical factors. These findings have important implications for epidemiological research on OCs and disease in this population, and underline the importance of selection and screening of OC users on the basis of knowledge of medical factors and lifestyle habits.

The role of the major identified risk factors for breast cancer was assessed using data from a hospital-based case-control study conducted in Northern Italy on 1108 women with histologically confirmed breast cancer and 1281 control subjects with a spectrum of acute conditions unrelated to any of the established or potential risk factors for breast disease. With reference to nulliparous women, the risk of breast cancer was below unity for those who first gave birth below age 25, and above unity for those with later first full-term pregnancy. However, in each stratum of age at first birth, the point estimate was below unity for women with five or more births. The relative risk for greater than or equal to 5 births compared with 1 or 2 was 0.6 (95% confidence interval = 0.4-0.9) when allowance was made for age at first birth. Likewise, there was a significant and independent effect of age at last birth which was evident in various strata of parity and age at first birth. The overall relative risk for last birth at 30 years or over compared with under 30 was 1.4 (95% confidence interval = 1.1-1.8). There was little relation of breast cancer risk with abortions or miscarriages. Breast cancer cases reported earlier menarche and later menopause; further, lifelong irregularities in menstrual pattern were less common among the cases (relative risk = 0.6, 95% confidence interval = 0.5-0.8). The risk estimates were elevated in women with positive history of benign breast disease, family history of breast cancer and greater body mass index.(ABSTRACT TRUNCATED AT 250 WORDS)

The relation between major indicators of sexual habits (age at first intercourse and total number of sexual partners), history of selected venereal diseases, and cervical neoplasia was investigated using data from a case-control study of 206 cases of cervical intraepithelial neoplasia compared with 206 age-matched outpatient controls, and of 327 cases of invasive cancer compared with 327 control subjects in hospital for acute conditions unrelated to any of the established or suspected risk factors for cervical cancer. The relative risks increased with decreasing age at first intercourse and increasing number of sexual partners both for intraepithelial and for invasive cancers. The effects of these two variables were independent, since they were only marginally affected by reciprocal adjustment, or by allowance for several other identified potential distorting factors. The negative association with age at first intercourse was particularly strong in the case of invasive cancers, with risk estimates over five-fold elevated for women reporting their first intercourse before age 18 compared with those aged over 22 years. This relation might be discussed in terms of multistage models of carcinogenesis, which predict that the incidence of epithelial carcinomas is a function of duration of exposure. In fact, when age was allowed for, the relative risks of cervical neoplasia were positively and strongly related with the total duration of the interval between age at diagnosis/interview and age at first intercourse. Clinical histories of several sexually transmitted diseases were positively associated with the risk of intraepithelial neoplasia. In particular, genital warts were reported by nine cases but no control subject. No such association, however, emerged for invasive carcinomas. Thus, the current findings confirm that, although intraepithelial neoplasia and invasive cervical cancer appear to share several important epidemiological features, the specific (infectious) agents implicated in dysplastic lesions probably differ to some extent from those causing invasive cancer.

We analysed data from a case-control investigation conducted in Milan, Northern Italy, to evaluate the relation between the use of combination oral contraceptives and the risk of cancers of the breast, ovary, endometrium and cervix uteri. For the present analysis, 776 cases of histologically confirmed breast cancer, 406 of epithelial ovarian cancer and 170 of endometrial cancer aged under 60 were compared with a group of 1,282 subjects below age 60 admitted for a spectrum of acute conditions apparently unrelated to oral contraceptive use or to any of the known or potential risk factors for the diseases under study. Likewise, 225 cases of invasive cervical cancer were compared with 225 age-matched inpatient controls, and 202 cases of cervical intra-epithelial neoplasia with 202 outpatient controls identified in the same screening clinics. The age-adjusted relative risk estimates for ever vs. never use of combination oral contraceptives were 1.04 (95% confidence interval (CI) 0.73-1.37) for breast cancer, 0.68 (95% CI = 0.48-0.97) for epithelial ovarian cancer, 0.50 (95% CI = 0.23-1.12) for endometrial cancer, 1.49 (95% CI = 0.88-2.55) for cervical cancer and 0.77 (95% CI = 0.50-1.18) for cervical intra-epithelial neoplasia. The risk of ovarian cancer decreased and that of invasive cervical cancer increased with longer duration of use. Neither duration of oral contraceptive use nor time since first or last use significantly altered a user's risk of other neoplasms considered. Likewise, analysis of sub-groups of age, parity or other potentially important covariates did not show any important interaction, and allowance for them by means of logistic regression did not materially modify any of the results. These data confirm that combination oral contraceptives confer some protection against ovarian and endometrial cancers but may increase the risk of invasive cervical cancer if used for several years, and indicate that the past or current pattern of oral contraceptive use in Italy is unlikely materially to affect the risk of breast cancer.

The risk of endometrial cancer in relation to nutrition and frequency of consumption of a few selected dietary items was evaluated id a case-control study of 206 patients with endometrial cancer and 206 control subjects with acute conditions unrelated to any of the established or potential risk factors for endometrial cancer. Obesity was strongly and positively associated with the risk of endometrial cancer, and several conditions related to body weight, such as early menarche, diabetes mellitus, or hypertension were more common in cases. The risk of endornetrial cancer was elevated in subjects reporting (on a subjective basis) greater fat (butter, margarine, and oil) intake (relative risk estimate for the higher compared to the lower scores equals 5.65, with 95% confidence interval of 2.76-11.55). Cases reported less frequent intake of green vegetables, fruit, and whole-grain foods: thus, the risk of endometrial cancer appeared inversely related to indices of beta-carotene and fiber intake. Furthermore, cases consumed milk, liver and fish less frequently than controls. No significant difference was noted between cases and controls in the frequency of intake of carrots, meat, eggs, ham, and cheese. Alcohol consumption WBS somewhat larger among the cases, but this trend in risk was not significant. Dietary information collected in this study probably is too limited and inconsistent to permit analysis of biologic correlates of these findings or discussion of their potential implications in terms of prevention on a public health scale. Nonetheless, the mere existence of differences in reported diet between endometrial cancer cases and controls is of interest, and may warrant further, more detailed investigation. Cancer 57:1248-1253, 1986. HERE IS a persuasive body of evidence that endoT metrial cancer is associated with body weight, as it occurs considerably more frequently in obese women.’ This is commonly explained in terms of increased aromatization of androgens to estrogens in adipose tissue, which is the major source of estrogens in postmenopausal women.2 The relation between body weight and endometrial cancer risk, however, is similarly evident in premenopausal women as well when circulating estrogens are chiefly ovarian in 0rigin.~9~ The link between nutrition and endometrial cancer, therefore, may be more complex, including the importance of sex hormone-binding globulins or the composition itself of adipose tissue, and potentially mediated through specific dietary components.

The relation between Papanicolau ("Pap") smear and the risk of cervical neoplasia was evaluated in a case-control study in which 145 women with cervical intra-epithelial neoplasia (CIN) were compared with 145 age-matched outpatient controls, and 191 cases of invasive cervical cancer were compared with 191 control subjects in hospital for acute conditions unrelated to any of the established or suspected risk factors for cervical cancer. Compared with women with no previous screening smear, the relative risk (RR) estimate for invasive cancer was 0·44 (with 95% confidence interval [CI]=0·24-0·80) for those who had had one smear and 0·20 (95% CI=0·13-0·32) for those who had had two or more smears. The corresponding estimates for CIN were 0·27 (95% CI=0·10-0·71) and 0·12 (95% CI=0·06-0·25), respectively. The risk estimates for intervals of more than 5, 3-5, and less than 3 years were 0·36, 0·18, and 0·10 for invasive cancer, and 0·45, 0·31, and 0·07 for CIN. These results were not materially modified by adjustment for the major risk factors for cervical cancer, such as indicators of socioeconomic status and sexual habits. According to the estimates of this study, 64% of invasive cervical cancers could be prevented by screening at intervals of more than 5 years, an additional 18% by reducing the interval to 3-5 years, and a further 8% to less than 3 years.

The relationship between consumption of decaffeinated coffee and acute myocardial infarction was analyzed in a case-control study conducted in Italy between 1983 and 1992. Case patients were 433 women with acute myocardial infarction, aged 24 to 69 years (median age, 52 years), and control subjects included 869 women in hospital for a wide spectrum of acute conditions, other than cardiovascular, neoplastic, digestive, and hormone-related diseases or conditions associated with long-term modification of diet. Regular use of decaffeinated coffee was reported by 11% of the case patients and 7% of the control subjects. Compared with women who did not drink decaffeinated coffee, the relative risk (RR) was 1.3 (95% confidence interval (CI), 0.8 to 2.2) for one cup/d and 2.1 (95% CI, 1.1 to 3.9) for 2 or more cups (chi 2(1) for trend = 5.62, P = 0.02). The estimates were somewhat higher after allowance for education, marital status, body mass index, and smoking status (RR for > or = 2 cups of decaffeinated coffee per day, 2.5; 95% CI, 1.2 to 4.9), and somewhat lower after further allowance for diabetes, hypertension, and hyperlipidemia (RR, 1.7; 95% CI, 0.8 to 3.6). There was no association between duration of use of decaffeinated coffee and infarction risk. The relationship between decaffeinated coffee and infarction was consistent across strata of age, education, smoking, and history of hyperlipidemia. Thus, a relationship of marginal significance was observed in this study between decaffeinated coffee and myocardial infarction, of similar magnitude to that described for caffeinated coffee. This indicates that (i) caffeine is unlikely to be a relevant factor in any potential coffee-myocardial infarction relationship, and (ii) shifting from caffeinated to decaffeinated coffee is unjustified in order to reduce any possible coffee-related infarction risk.

The relationship between menstrual and reproductive factors and subsequent risk of coronary heart disease was investigated in a hospital-based case-control study of 202 women with acute myocardial infarction and 374 control subjects admitted for a wide spectrum of acute conditions unrelated to any of the established risk factors for ischemic heart disease. No consistent association was observed with age at menarche or menopausal status, but women with a lifelong irregular menstrual cycle pattern were at significantly elevated risk of myocardial infarction (relative risk = 1.8, 95% confidence interval = 1.1 to 2.9). No clear trend in risk was evident with the number of livebirths, miscarriages, or induced abortions. However, women whose first pregnancy or livebirth occurred before age 20 years showed elevated risks of subsequent myocardial infarction compared with nulliparous ones (relative risks = 2.3; 95% confidence interval = 1.1 to 4.9), and there was a significant trend of increasing risk with earlier first birth. These associations were evident in both younger and middle-age women and were not explained by allowance for several identified potential confounding factors.

The relationship between cigarette smoking and risk of cervical neoplasia was evaluated in a case-control study of 183 women with cervical intraepithelial neoplasia compared with 183 age-matched outpatient controls, and of 230 cases of invasive cervical cancer compared with 230 controls in hospital for acute conditions unrelated to any of the identified or suspected risk factors for cervical cancer. Current cigarette smoking was associated with an elevated risk of cervical intraepithelial neoplasia (relative risk = 1.76, 95 per cent confidence interval = 1.14-2.27) and of invasive cancer (relative risk = 1.69, 95 per cent confidence interval = 1.08-2.65). This association was only partially accounted for by a large number of identified potential confounding factors, including indicators of socioeconomic status and sexual habits. The risk increased with the number of cigarettes smoked and was apparently greater for women who started smoking at younger ages. The relative risk of intraepithelial neoplasia was elevated within 20 years after the start of smoking and showed little tendency to increase with increasing duration. On the other hand, the risk of invasive cervical cancer was apparently unaffected by smoking less than 20 years and increased steadily thereafter, reaching a point estimate of 3.63 after 40 years or more. If one assumes that intraepithelial neoplasia is an early stage of cervical cancer, this pattern of risk is consistent with the predictions from the multistage theory of carcinogenesis, if the effect of smoking is on one of the earlier stages. No obvious distorting factors, apart from the play of chance, is likely to produce such a risk pattern.

The relation between coffee consumption and the risk of acute myocardial infarction was evaluated in a hospital-based case-control study conducted in northern Italy between 1983 and 1987. The study consisted of 262 women with acute myocardial infarction and 519 controls admitted to the hospital for acute, nondigestive tract disorders. Information was obtained on the average number of cups of coffee or decaffeinated coffee consumed per day before the onset of the disease which led to hospital admission and on the total duration in years of the habit. There was a positive association between heavy coffee drinking and risk of myocardial infarction (relative risk (RR) = 2.7 for consumption of four cups or more per day). After allowance for smoking and other relevant covariates, the relative risk was not elevated for consumption of up to three cups per day, but still above unity for consumption of four or more cups per day (RR = 1.7), and the multivariate trend in risk was still significant (X1(2) = 5.14, p = 0.02). The risk estimates were grossly elevated among hyperlipidemic women (multivariate RR = 7.6 for moderate and 17.9 for heavy coffee drinkers). As a result of small absolute numbers, these estimates were largely unstable and the interaction between coffee and hyperlipidemia was not statistically significant. Such estimates, nonetheless, are of potential interest in terms of etiologic correlates and implications for prevention.