Correspondence re: Simon et al., Do thyroid disorders increase the risk of breast cancer? 11: 1574-1578, 2002.
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Adult↗
Biomedical subjects
Silvia Franceschi
Publications and source records attributed to Silvia Franceschi.
Influence of the Mediterranean diet on the risk of cancers of the upper aerodigestive tract.
The hypothesis that the Mediterranean diet has a beneficial role on the risk of cancers of the upper aerodigestive tract has been evaluated using data from three case-control studies conducted in Italy between 1992 and 2000. The first study included 598 cases with incident, histologically confirmed cancers of the oral cavity and pharynx and 1491 hospital controls admitted to the same network of hospitals as cases for acute, nonneoplastic diseases. The second one included 304 subjects with squamous cell carcinoma of the esophagus and 743 controls. The third one included 460 laryngeal cancer cases and 1088 controls. A score summarizing eight of the major characteristics of the Mediterranean diet was used. Odds ratios and corresponding 95% confidence intervals (CIs) for increasing levels of this score were estimated using unconditional regression models, adjusted for age, sex, study center, years of education, tobacco consumption, body mass index, and total energy intake. For all cancers considered, a reduced risk was found for increasing levels of the Mediterranean score: the odds ratios for subjects with six or more Mediterranean characteristics, compared with those with less than three characteristics, were 0.40 (95% CI, 0.26-0.62) for oral and pharyngeal, 0.26 (95% CI, 0.13-0.51) for esophageal, and 0.23 (95% CI, 0.13-0.40) for laryngeal cancer. All of the estimates were consistent in strata of the major identified risk factors for these neoplasms. This study provides evidence that an a priori defined nutritional pattern, which includes several aspects of the Mediterranean diet, favorably affects the risk of cancers of the upper aerodigestive tract.
Aged↗
Dietary folate and colorectal cancer.
Folate may be inversely related to colorectal cancer risk, possibly in combination with low methionine and high alcohol consumption. We considered, therefore, the relation between folate and colorectal cancer in a multicentric case-control study of 1,953 cases and 4,154 controls from Italy, i.e., a population with frequent regular alcohol drinking. In the overall data set, the odds ratio (OR) was 0.72 for the highest quintile of folate, and the continuous OR per 100 microg was 0.86. The inverse relation was similar in men and women and somewhat stronger for the rectum (OR = 0.59 for the highest quintile) compared to the colon (OR = 0.81). It was also somewhat stronger in the highest tertile of alcohol drinking (OR = 0.65), though trends were not heterogeneous across strata of alcohol, whereas no appreciable difference was observed across strata of methionine intake. Compared to subjects reporting low alcohol, high methionine and high folate intake, the OR was 1.83 for those reporting high alcohol, low methionine and low folate intake. The present findings support a favorable role of folate in colorectal carcinogenesis.
Adult↗
Attributable risk for familial breast cancer.
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Breast Neoplasms↗
Alcohol drinking outside meals and cancers of the upper aero-digestive tract.
In our integrated series of case-control studies conducted in Italy and Switzerland (324 oral, 397 pharyngeal, 271 oesophageal, 506 laryngeal cancers and 3,263 controls), individuals who also drank alcoholic beverages outside meals showed an increased risk compared to those who drank at meals only. At any alcohol intake level, subjects also drinking between meals showed a more elevated risk of developing an upper aero-digestive tract cancer than subjects drinking only at meals. After adjustment for potential covariates, and, after allowance for the number of daily drinks to adjust for different alcohol-intake levels, the odds ratios for subjects reporting drinking outside meals were 1.5 (95% confidence interval [CI]: 1.0-2.2) for oral, 1.8 (95% CI: 1.3-2.5) for pharyngeal, 1.7 (95% CI: 1.2-2.5) for oesophageal and 1.2 (95% CI: 0.9-1.7) for laryngeal cancers. Our findings show that drinking pattern with respect to food consumption may influence alcohol carcinogenesis in the upper digestive and respiratory tract. An "alcohol washing effect" by chewing and swallowing is suggested.
Adult↗
Long-term effects of oral contraceptives on ovarian cancer risk.
Several epidemiologic studies have reported a protective effect of oral contraceptives (OCs) on ovarian cancer. However, there remain open issues, including better quantification of time-related factors such as time since last use, age at first use and time since first use. We performed a collaborative reanalysis of 6 case-control studies conducted between 1978 and 1999 in the United Kingdom, Greece and Italy, including a total of 2,768 incident, histologically confirmed cases of epithelial ovarian cancer and 6,274 hospital controls under age 70 years. A reduced risk of ovarian cancer was found for ever- compared to never-users [odds ratio (OR) = 0.66, 95% confidence interval (CI) 0.56-0.79], and a stronger reduction was observed for women who had used OCs for > or =5 years (OR = 0.50, 95% CI 0.33-0.76) compared to those who had used them for <5 years. The protective effect of OCs on ovarian cancer was consistent across strata of age, parity, menopausal status and family history of breast or ovarian cancer. After allowance for duration of use, no other time factor was related to ovarian cancer risk: the reduced risk was similar for women who stopped OC use > or =20 years before compared to <10 years; likewise, no significant modification of risk reduction was observed for age at first OC use and time since first OC use. The present analysis indicates that, after taking into account duration of OC use, the OC protection from ovarian cancer persists for a long time after stopping use.
Adult↗
Herpes simplex virus-2 as a human papillomavirus cofactor in the etiology of invasive cervical cancer.
BACKGROUND: Human papillomavirus (HPV) infection is the main cause of invasive cervical cancer, but cofactors may act in conjunction with HPV. We performed a pooled analysis of seven case-control studies to examine the effect of one possible HPV cofactor, herpes simplex virus-2 (HSV-2) infection, in the etiology of invasive cervical cancer. METHODS: Blood and exfoliated cervical specimens were obtained from 1263 case patients with invasive cervical cancer (1158 with squamous-cell carcinomas and 105 with adeno- or adenosquamous-cell carcinomas) and 1117 age-matched control subjects. Western blot analysis and/or an enzyme-linked immunosorbent assay were used to detect type-specific serum antibodies to HSV-2 and HSV-1, and Chlamydia trachomatis serum antibodies were detected using a micro-immunofluorescence assay. HPV DNA was detected using a polymerase chain reaction assay. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were computed from unconditional logistic regression models. RESULTS: Overall, HSV-2 seropositivity was higher among case patients with squamous-cell carcinoma (44.4%, 95% CI = 41.5% to 47.3%) or adeno- or adenosquamous-cell carcinoma (43.8%, 95% CI = 34.2% to 53.5%) than among control subjects (25.6%, 95% CI = 23.0% to 28.2%). Cervical specimens from 1098 (94.8%) squamous-cell carcinoma case patients, 95 (90.5%) adeno- or adenosquamous carcinoma case patients, and 164 (14.7%) control subjects were positive for HPV DNA. Among the HPV DNA-positive women, HSV-2 seropositivity was associated with increased risks of squamous-cell carcinoma (OR = 2.19, 95% CI = 1.41 to 3.40) and adeno- or adenosquamous-cell carcinoma (OR = 3.37, 95% CI = 1.47 to 7.74) after adjustment for potential confounders. A similar association between HSV-2 seropositivity and squamous-cell carcinoma risk was observed after further controlling for markers of sexual behavior (OR = 1.96, 95% CI = 1.24 to 3.09). Among control subjects, HSV-2 seropositivity was associated with markers of sexual behavior, but not with cervical HPV DNA positivity. CONCLUSION: HSV-2 infection may act in conjunction with HPV infection to increase the risk of invasive cervical carcinoma.
Adult↗
Food groups and laryngeal cancer risk: a case-control study from Italy and Switzerland.
Besides tobacco and alcohol, diet has been thought to be associated with laryngeal cancer risk. We thus analyzed the role of various food groups, as well as specific seasoning fats, in a case-control study conducted in Northern Italy and the Swiss Canton of Vaud from 1992 to 2000. Our study included 527 incident, histologically confirmed cases and 1,297 frequency-matched controls, selected among patients admitted to the same hospitals as cases for acute, nonneoplastic conditions, unrelated to smoking, alcohol consumption and long-term modifications of diet. The subjects' usual diet was investigated through a validated food frequency questionnaire, including 78 foods and beverages. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional multiple logistic regression models. After adjustment for major confounding factors, a significant trend of increasing risk was observed for eggs (OR = 1.7 for the highest compared to the lowest quintile), red meat (OR = 3.1), processed meat (OR = 1.7), fish (OR = 1.6) and sugars (OR = 1.6). Significant inverse associations were observed for pulses (OR = 0.7), raw vegetables (OR = 0.2), cooked vegetables (OR = 0.3), citrus fruit (OR = 0.6) and other fruit (OR = 0.5). In regard to seasoning fats, a significant reduction of cancer risk was observed for olive oil (OR = 0.4) and specific seed oils (OR = 0.6), while mixed seed oils were directly associated with laryngeal cancer risk (OR = 2.2). Our study suggests that increasing vegetables and fruit, decreasing meat consumption and perhaps substituting olive oil or specific seed oils for other types of seasoning lipids might help reduce laryngeal cancer risk.
Adult↗
Post-menopausal hormonal therapy and gallbladder cancer risk.
The relation between post-menopausal hormone replacement therapy (HRT) and gallbladder cancer was analyzed in women above age 45 years, using data of a case-control study conducted in Italy between 1985 and 1997, on 31 incident, histologically confirmed cases and 3,702 controls in hospital for acute, non-neoplastic conditions. The multivariate odds ratio (OR) was 3.2 (95% confidence interval: 1.1-9.3) for those who had ever used HRT and the OR tended to rise with longer duration. Although based on small numbers, due to the rarity of the disease, these findings provide the first direct epidemiological evidence of an association between HRT and gallbladder cancer.
Aged↗
Male circumcision, penile human papillomavirus infection, and cervical cancer in female partners.
BACKGROUND: It is uncertain whether male circumcision reduces the risks of penile human papillomavirus (HPV) infection in the man and of cervical cancer in his female partner. METHODS: We pooled data on 1913 couples enrolled in one of seven case-control studies of cervical carcinoma in situ and cervical cancer in five countries. Circumcision status was self-reported, and the accuracy of the data was confirmed by physical examination at three study sites. The presence or absence of penile HPV DNA was assessed by a polymerase-chain-reaction assay in 1520 men and yielded a valid result in the case of 1139 men (74.9 percent). RESULTS: Penile HPV was detected in 166 of the 847 uncircumcised men (19.6 percent) and in 16 of the 292 circumcised men (5.5 percent). After adjustment for age at first intercourse, lifetime number of sexual partners, and other potential confounders, circumcised men were less likely than uncircumcised men to have HPV infection (odds ratio, 0.37; 95 percent confidence interval, 0.16 to 0.85). Monogamous women whose male partners had six or more sexual partners and were circumcised had a lower risk of cervical cancer than women whose partners were uncircumcised (adjusted odds ratio, 0.42; 95 percent confidence interval, 0.23 to 0.79). Results were similar in the subgroup of men in whom circumcision was confirmed by medical examination. CONCLUSIONS: Male circumcision is associated with a reduced risk of penile HPV infection and, in the case of men with a history of multiple sexual partners, a reduced risk of cervical cancer in their current female partners.
Adult↗
Effect of oral contraceptives on risk of cervical cancer in women with human papillomavirus infection: the IARC multicentric case-control study.
BACKGROUND: Use of oral contraceptives could increase risk of cervical cancer; however the effect of human papillomavirus (HPV), the main cause of cervical cancer, is not usually taken into account. We aimed to assess how use of oral contraceptives affected risk of cervical cancer in women who tested positive for HPV DNA. METHODS: We pooled data from eight case-control studies of patients with histologically confirmed invasive cervical carcinoma (ICC) and from two studies of patients with carcinoma in situ (ISC). Information about use of oral contraceptives was obtained from personal interviews. Effects were estimated as odds ratios, with logistic-regression models adjusted for possible confounders. FINDINGS: 1465 of 1561 (94%) patients with ICC, 211 of 292 (72%) with ISC, and 255 of 1916 (13%) controls were positive for HPV DNA. Compared with never-users, patients who had used oral contraceptives for fewer than 5 years did not have increased risk of cervical cancer (odds ratio 0.73; 95% CI 0.52-1.03). The odds ratio for use of oral contraceptives was 2.82 (95% CI 1.46-5.42) for 5-9 years, and 4.03 (2.09-8.02) for use for 10 years or longer, and these risks did not vary by time since first or last use. INTERPRETATION: Long-term use of oral contraceptives could be a cofactor that increases risk of cervical carcinoma by up to four-fold in women who are positive for cervical HPV DNA. In the absence of worldwide information about HPV status, extra effort should be made to include long-term users of oral contraceptives in cervical screening programmes.
Age of Onset↗
Role of parity and human papillomavirus in cervical cancer: the IARC multicentric case-control study.
BACKGROUND: High parity has long been suspected of being associated with an increased risk of cervical cancer, but previous analyses of this association have not taken the strong effect of human papillomavirus (HPV) into account. To assess the role of reproductive factors in the progression from HPV infection to cancer, we did a pooled analysis including only HPV-positive women. METHODS: We pooled data from eight case-control studies on invasive cervical carcinoma (ICC) and two on in-situ carcinoma (ISC) from four continents. 1465 patients with squamous-cell ICCs, 211 with ISCs, 124 with adenocarcinomas or adenosquamous ICCs, and 255 control women, all positive for HPV DNA by PCR-based assays, were analysed. We calculated pooled odds ratios by means of unconditional multiple logistic regression models, and adjusted them for sexual and non-sexual confounding factors. The 95% CI were estimated by treating the odds ratio as floating absolute risk. FINDINGS: We found a direct association between the number of full-term pregnancies and squamous-cell cancer risk: the odds ratio for seven full-term pregnancies or more was 3.8 (95% CI 2.7-5.5) compared with nulliparous women, and 2.3 (1.6-3.2) compared with women who had one or two full-term pregnancies. There was no significant association between risk of adenocarcinoma or adenosquamous carcinoma and number of full-term pregnancies. INTERPRETATION: High parity increases the risk of squamous-cell carcinoma of the cervix among HPV-positive women. A general decline in parity might therefore partly explain the reduction in cervical cancer recently seen in most countries.
Adenocarcinoma↗
Invasive cervical cancer as an AIDS-defining illness in Europe.
OBJECTIVE(S): To evaluate the frequency and correlates of invasive cervical cancer (ICC) as an AIDS-defining illness (ADI) in Europe. DESIGN: Statistical analysis of data from: national AIDS surveillance systems of 15 European countries with >or= 50 female AIDS cases; and from population-based cancer registries of the same nations. METHODS: AIDS cases notified between 1993 (when ICC was included among ADI) and 1999 in women aged 20-49 years were taken into consideration. The association between the presence of ICC as an ADI and potential determinants was assessed by calculation of odds ratios (OR) and 95% confidence intervals (CI). Country-specific incidence rates of ICC in women aged 20-49 years were correlated with selected AIDS-associated variables by means of the Pearson correlation coefficient (r). RESULTS: The OR of having ICC as an ADI increased with age and was significantly elevated in southern (3.1) and central (2.5) compared with northern Europe. It was also increased among injecting drug users (IDU; 1.5). The proportion of ICC as ADI was inversely correlated with incidence rates of ICC in the general female population, but directly correlated with the proportion of IDU among female AIDS cases. CONCLUSIONS: The frequency of ICC as an ADI in Europe was independent from the background risk of ICC in the general population. It was higher where IDU predominated among female AIDS cases and where population-based ICC screening programs were less effective.
Acquired Immunodeficiency Syndrome↗
Oral cancer in southern India: the influence of smoking, drinking, paan-chewing and oral hygiene.
Between 1996 and 1999 we carried out a case-control study in 3 areas in Southern India (Bangalore, Madras and Trivandrum) including 591 incident cases of cancer of the oral cavity (282 women) and 582 hospital controls (290 women), frequency-matched with cases by age and gender. Odds ratios (ORs) and 95% confidence intervals (CIs) were obtained from unconditional multiple logistic regressions and adjusted for age, gender, center, education, chewing habit and (men only) smoking and drinking habits. Low educational attainment, occupation as a farmer or manual worker and various indicators of poor oral hygiene were associated with significantly increased risk. An OR of 2.5 (95% CI 1.4-4.4) was found in men for smoking > or = 20 bidi or equivalents versus 0/day. The OR for alcohol drinking was 2.2 (95% CI 1.4-3.3). The OR for paan chewing was more elevated among women (OR 42; 95% CI 24-76) than among men (OR 5.1; 95% CI 3.4-7.8). A similar OR was found among chewers of paan with (OR 6.1 in men and 46 in women) and without tobacco (OR 4.2 in men and 16.4 in women). Among men, 35% of oral cancer is attributable to the combination of smoking and alcohol drinking and 49% to pan-tobacco chewing. Among women, chewing and poor oral hygiene explained 95% of oral cancer.
Adult↗
Evidence for Chlamydia trachomatis as a human papillomavirus cofactor in the etiology of invasive cervical cancer in Brazil and the Philippines.
Chlamydia trachomatis infection was examined as a cause of invasive cervical cancer (ICC) among women with human papillomavirus (HPV) infection. In total, 499 women with incident ICC (ICC patients) and 539 control patients from São Paulo, Brazil, and Manila, the Philippines, were included. C. trachomatis antibodies were detected by microimmunofluorescence assay. Presence of HPV DNA in cervical specimens was determined by a polymerase chain reaction-based assay. C. trachomatis seropositivity was associated with sexual behavior but not with HPV infection. C. trachomatis increased the risk of squamous cervical cancer among HPV-positive women (odds ratio, 2.1; 95% confidence interval, 1.1-4.0). Results were similar in both countries. There was a suggestion of increasing squamous cancer risk with increasing C. trachomatis antibody titers. This large study examined C. trachomatis and cervical cancer, taking into account the central role of HPV infection. C. trachomatis infection was found to be a possible cofactor of HPV in the etiology of squamous cervical cancer, and its effect may be mediated by chronic inflammation.
Adult↗
Smoking and other risk factors for bladder cancer in women.
BACKGROUND: Bladder cancer is three to five times more frequent in men than in women, and hence only a few studies have focused only on females. METHODS: A case-control study was conducted between 1985 and 1992 in two areas of northern Italy, and included 110 women with histologically confirmed bladder cancer and 298 controls, admitted to the same network of hospitals of cases for acute, non-neoplastic, non-urinary or genital tract diseases. Multivariate odds ratios (ORs) were computed using unconditional multiple logistic regression. RESULTS: Compared to never smokers, current smokers (OR = 2.87) had significantly elevated risks of bladder cancer. High intake of vegetables was inversely related to the disease (OR = 0.32), while history of occupation in chemical, dyes/paints or pharmaceutical industry (OR = 3.01) was directly associated to risk of bladder cancer. The OR was 3.29 for ever use of menopause hormone replacement therapy. CONCLUSIONS: This study confirms that cigarette smoking is the prominent risk factor for bladder cancer in women as in men, with similar relations in both sexes. It also confirms that selected occupational factors are related to bladder cancer risk, and supports a favourable role of vegetables. The apparent relation with hormone replacement therapy in menopause needs interpretation and further investigation.
Adult↗
Expression of cyclin-dependent kinase inhibitor p27(Kip1) in AIDS-related diffuse large-cell lymphomas is associated with Epstein-Barr virus-encoded latent membrane protein 1.
Knowledge of the role of cell-cycle regulators in the pathogenesis of acquired immune deficiency syndrome-related non-Hodgkin's lymphomas (AIDS-NHLs) is scarce. Here we analyzed 86 systemic AIDS-NHLs and 20 AIDS-primary central nervous system lymphomas for expression of p27(Kip1), a negative regulator of cell-cycle progression belonging to the Kip family of cyclin-dependent kinase inhibitors. In parallel, we investigated the relationship between p27(Kip1), the lymphoma proliferation index, Epstein-Barr virus status, expression of cellular cyclin D3 and cyclin D1, and B-cell differentiation stage. We report that AIDS-immunoblastic lymphomas (AIDS-IBLs), either systemic or primarily localized to the central nervous system, consistently express p27(Kip1) protein (19 of 24 and 10 of 14, respectively) despite the high proliferative rate of the lymphoma clone, suggesting a failure of p27(Kip1) to inhibit the cell cycle in AIDS-IBL. Conversely, the remaining systemic AIDS-NHLs and AIDS-primary central nervous system lymphomas preferentially fail to express p27(Kip1). Expression of p27(Kip1) in Epstein-Barr virus-positive AIDS-NHLs generally associates with latent membrane protein 1 (LMP1) expression and is related to a late stage of B-cell differentiation, characterized by the BCL-6-/MUM1+/syn-1+/- phenotypic profile, whereas it seems to be unrelated to the expression of cellular cyclins. In B cells in vitro, induction of LMP-1 expression under the control of inducible promoters up-regulates expression of p27(Kip1), thus providing a putative mechanistic explanation for the association between LMP1 and p27(Kip1) observed in vivo. Overall, these data show that AIDS-IBL pathogenesis is characterized by loss of the inverse relationship between p27(Kip1) positivity and tumor growth fraction that is otherwise generally observed in normal lymphoid tissues and in most other types of NHLs.
Arabidopsis Proteins↗
Strategies for HPV prevention.
The HPV types that cause cervical cancer are sexually transmitted, but there is little evidence that infection can be avoided by behavioral change, such as condom use. In contrast, prophylactic vaccines against HPV infection are likely to have high efficacy. In principle, the effectiveness of HPV vaccination as a strategy for cervical cancer control can be measured either by monitoring secular trends in cervical cancer incidence or by conducting randomized trials. The former approach is unlikely to provide convincing evidence of effectiveness, since cervical cancer rates are subject to strong secular trends that are independent of intervention measures. A few phase III trials of HPV prophylactic vaccines are being started. Such trials are very expensive studies involving frequent and complicated investigations. It is important, however, to start as soon as possible simpler trials which may demonstrate the effectiveness of HPV vaccine in field conditions, i.e. in developing countries which do not have the resources to mount effective cytology-based screening programs, yet suffer the major burden of mortality from cervical cancer. Such trials may capture a difference in the most severe, and rarest, preinvasive cervical lesions. The design of such studies is briefly considered for two areas: Southern India and South Korea. Finally, projections of the number of cases of cervical cancer following the introduction of mass vaccination are given for developed and developing countries.
Female↗