Considerable experimental and epidemiological evidence suggests that elevated endogenous sex steroids -notably androgens and oestrogens -promote breast tumour development. In spite of this evidence, postmenopausal androgen replacement therapy with dehydroepiandrosterone (DHEA) or testosterone has been advocated for the prevention of osteoporosis and improved sexual wellbeing. We have conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition. Levels of DHEA sulphate (DHEAS), (D4-androstenedione), testosterone, oestrone, oestradiol and sex-hormone binding globulin (SHBG) were measured in prediagnostic serum samples of 677 postmenopausal women who subsequently developed breast cancer and 1309 matched control subjects. Levels of free testosterone and free oestradiol were calculated from absolute concentrations of testosterone, oestradiol and SHBG. Logistic regression models were used to estimate relative risks of breast cancer by quintiles of hormone concentrations. For all sex steroidsthe androgens as well as the oestrogens -elevated serum levels were positively associated with breast cancer risk, while SHBG levels were inversely related to risk. For the androgens, relative risk

Environmental carcinogens contained in air pollution, such as polycyclic aromatic hydrocarbons, aromatic amines or N-nitroso compounds, predominantly form DNA adducts but can also generate interstrand cross-links and reactive oxygen species. If unrepaired, such lesions increase the risk of somatic mutations and cancer. Our study investigated the relationships between 22 polymorphisms (and their haplotypes) in 16 DNA repair genes belonging to different repair pathways in 1094 controls and 567 cancer cases (bladder cancer, 131; lung cancer, 134; oral-pharyngeal cancer, 41; laryngeal cancer, 47; leukaemia, 179; death from emphysema and chronic obstructive pulmonary disease, 84). The design was a case-control study nested within a prospective investigation. Among the many comparisons, few polymorphisms were associated with the diseases at the univariate analysis: XRCC1-399 Gln/Gln variant homozygotes [odds ratios (OR) = 2.20, 95% confidence intervals (CI) = 1.16-4.17] and XRCC3-241 Met/Met homozygotes (OR = 0.51, 95% CI = 0.27-0.96) and leukaemia. The recessive model in the stepwise multivariate analysis revealed a possible protective effect of XRCC1-399Gln/Gln in lung cancer (OR = 0.22, 95% CI = 0.05-0.98), and confirmed an opposite effect (OR = 2.47, 95% CI = 1.02-6.02) in the leukaemia group. Our results also suggest that the XPD/ERCC1-GAT haplotype may modulate leukaemia (OR = 1.28, 95% CI = 1.02-1.61), bladder cancer (OR = 1.38, 95% CI = 1.06-1.79) and possibly other cancer risks. Further investigations of the combined effects of polymorphisms within these DNA repair genes, smoking and other risk factors may help to clarify the influence of genetic variation in the carcinogenic process.

SummaryThe aim of this study was to investigate constitutional and environmental determinants of nonmelanocytic skin cancer among different populations from south Europe. Between 1989 and 1993 we interviewed incident cases and a random population sample of controls from five centres where a cancer registry was operating, whereas we selected a sample of hospital-based cases and controls from three other centres. Controls were stratified according to the age and sex distribution of cases. In all, 1549 cases of basal cell carcinoma (BCC), 228 of squamous cell carcinoma (SCC) and 1795 controls were interviewed. Both cancers affected primarily sun-exposed sites such as face, head and neck, but the prevalence of BCC on the trunk was higher than for SCC. Pigmentary traits such as hair and eye colour as well as tendency to sunburn were strong and independent indicators of risk for both BCC and SCC. In SCC, adjusted odds ratios (ORs) ranged from 1.6 for fair hair colour to 12.5 for red hair. Light-blonde hair entailed a risk of about 2 for BCC. Pale eye colour was associated with a risk of 1.8 for SCC and 1.4 for BCC. Subjects who always burn and never tan showed an adjusted OR of 2.7 for BCC and 2.0 for SCC. A history of sunburns and a young age at first sunburn were associated with an increased risk for BCC only (OR 1.7). Pigmentary traits and sun sensitivity of the skin confirmed their role as risk indicators. The effect of sunburns, as an indicator of both exposure and sun sensitivity of the skin, is less clear. Nevertheless, its association with BCC suggests, by analogy with melanoma, a relationship with intense sun exposure. Converseley, SCC would require prolonged exposure to sunlight.

Elevated blood pressure has been implicated as a risk factor for renal cell carcinoma (RCC), but prospective studies were confined to men and did not consider the effect of antihypertensive medication. The authors examined the relation among blood pressure, antihypertensive medication, and RCC in the European Prospective Investigation into Cancer and Nutrition (EPIC). Blood pressure was measured in 296,638 women and men, recruited in eight European countries during 1992-1998, 254,935 of whom provided information on antihypertensive medication. During a mean follow-up of 6.2 years, 250 cases of RCC were identified. Blood pressure was independently associated with risk of RCC. The relative risks for the highest versus the lowest category of systolic (>/=160 mmHg vs. <120 mmHg) and diastolic (>/=100 mmHg vs. <80 mmHg) blood pressures were 2.48 (95% confidence interval: 1.53, 4.02) and 2.34 (95% confidence interval: 1.54, 3.55). Risk estimates did not significantly differ according to sex or use of antihypertensive medication. Individuals taking antihypertensive drugs were not at a significantly increased risk unless blood pressure was poorly controlled. These results support the hypothesis that hypertension, rather than its medications, increases the risk of RCC in both sexes, while effective blood pressure control may lower the risk.

A population-based case-control study of cervical cancer was conducted in Spain and Colombia to assess the relationship between cervical cancer and exposure to human papillomavirus (HPV), selected aspects of sexual and reproductive behaviour, use of oral contraceptives, screening practices and smoking. The study included 436 cases of histologically confirmed squamous-cell carcinoma and 387 age-stratified controls randomly selected from the general population that generated the cases. The presence of HPV DNA in cervical scrapes was assessed by PCR-based methods and was the strongest risk factor (OR = 23.8; 13.4-42.0). Risk estimates for any other factor were only slightly modified after adjusting for HPV status. Among women found positive for HPV DNA, only the use of oral contraceptives was a risk factor for cervical cancer (OR = 6.5; 1.3-31.4 for ever vs. never use). Patients with cervical cancer who were HPV DNA-negative retained most of the established epidemiological features of this disease. This suggests that some instances of HPV infection went undetected or that other sexually transmitted factor(s) contribute to the causation of cervical cancer. Early age at first intercourse (OR = 4.3; 2.1-9.0 for age < 16 vs. 24+) and early age at first birth (OR = 5.0; 1.8-14.2 for age < 16 vs. 24+) were associated with increased risk of cervical cancer; these effects were independent of one another. Low educational level was a risk factor (OR = 2.5; 1.6-3.9). Number of sexual partners was in our study a surrogate for HPV infection. Smoking and parity after age 24 were weakly and inconsistently associated with the risk of cervical cancer. Previous screening (OR = 0.7; 0.5-1.0) and ever having undergone a Caesarean section (OR = 0.4; 0.2-0.8) were protective factors.