Combined effect of low-penetrant SNPs on breast cancer risk.

BACKGROUND: Although many low-penetrant genetic risk factors for breast cancer have been discovered, knowledge about the effect of multiple risk alleles is limited, especially in women <50 years. We therefore investigated the association between multiple risk alleles and breast cancer risk as well as individual effects according to age-approximated pre- and post-menopausal status. METHODS: Ten previously described breast cancer-associated single-nucleotide polymorphisms (SNPs) were analysed in a joint European biobank-based study comprising 3584 breast cancer cases and 5063 cancer-free controls. Genotyping was performed using MALDI-TOF mass spectrometry, and odds ratios were estimated using logistic regression. RESULTS: Significant associations with breast cancer were confirmed for 7 of the 10 SNPs. Analysis of the joint effect of the original 10 as well as the statistically significant 7 SNPs (rs2981582, rs3803662, rs889312, rs13387042, rs13281615, rs3817198 and rs981782) found a highly significant trend for increasing breast cancer risk with increasing number of risk alleles (P-trend 5.6 × 10(-20) and 1.5 × 10(-25), respectively). Odds ratio for breast cancer of 1.84 (95% confidence interval (CI): 1.59-2.14; 10 SNPs) and 2.12 (95% CI: 1.80-2.50; 7 SNPs) was seen for the maximum vs the minimum number of risk alleles. Additionally, one of the examined SNPs (rs981782 in HCN1) had a protective effect that was significantly stronger in premenopausal women (P-value: 7.9 × 10(-4)). CONCLUSION: The strongly increasing risk seen when combining many low-penetrant risk alleles supports the polygenic inheritance model of breast cancer.

Postmenopausal circulating levels of 2- and 16α-hydroxyestrone and risk of endometrial cancer.

BACKGROUND: It has been suggested that the relative importance of oestrogen-metabolising pathways may affect the risk of oestrogen-dependent tumours including endometrial cancer. One hypothesis is that the 2-hydroxy pathway is protective, whereas the 16α-hydroxy pathway is harmful. METHODS: We conducted a case-control study nested within three prospective cohorts to assess whether the circulating 2-hydroxyestrone : 16α-hydroxyestrone (2-OHE1 : 16α-OHE1) ratio is inversely associated with endometrial cancer risk in postmenopausal women. A total of 179 cases and 336 controls, matching cases on cohort, age and date of blood donation, were included. Levels of 2-OHE1 and 16α-OHE1 were measured using a monoclonal antibody-based enzyme assay. RESULTS: Endometrial cancer risk increased with increasing levels of both metabolites, with odds ratios in the top tertiles of 2.4 (95% CI=1.3, 4.6; P(trend)=0.007) for 2-OHE1 and 1.9 (95% CI=1.1, 3.5; P(trend)=0.03) for 16α-OHE1 in analyses adjusting for endometrial cancer risk factors. These associations were attenuated and no longer statistically significant after further adjustment for oestrone or oestradiol levels. No significant association was observed for the 2-OHE1 : 16α-OHE1 ratio. CONCLUSION: Our results do not support the hypothesis that greater metabolism of oestrogen via the 2-OH pathway, relative to the 16α-OH pathway, protects against endometrial cancer.

Circulating sex hormones and breast cancer risk factors in postmenopausal women: reanalysis of 13 studies.

BACKGROUND: Breast cancer risk for postmenopausal women is positively associated with circulating concentrations of oestrogens and androgens, but the determinants of these hormones are not well understood. METHODS: Cross-sectional analyses of breast cancer risk factors and circulating hormone concentrations in more than 6000 postmenopausal women controls in 13 prospective studies. RESULTS: Concentrations of all hormones were lower in older than younger women, with the largest difference for dehydroepiandrosterone sulphate (DHEAS), whereas sex hormone-binding globulin (SHBG) was higher in the older women. Androgens were lower in women with bilateral ovariectomy than in naturally postmenopausal women, with the largest difference for free testosterone. All hormones were higher in obese than lean women, with the largest difference for free oestradiol, whereas SHBG was lower in obese women. Smokers of 15+ cigarettes per day had higher levels of all hormones than non-smokers, with the largest difference for testosterone. Drinkers of 20+ g alcohol per day had higher levels of all hormones, but lower SHBG, than non-drinkers, with the largest difference for DHEAS. Hormone concentrations were not strongly related to age at menarche, parity, age at first full-term pregnancy or family history of breast cancer. CONCLUSION: Sex hormone concentrations were strongly associated with several established or suspected risk factors for breast cancer, and may mediate the effects of these factors on breast cancer risk.

Dietary beta-carotene, vitamin C and E intake and breast cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC).

So far, studies on dietary antioxidant intake, including beta-carotene, vitamin C and vitamin E, and breast cancer risk are inconclusive. Thus, we addressed this question in the European Prospective Investigation into Cancer and Nutrition. During a median follow-up time of 8.8 years, 7,502 primary invasive breast cancer cases were identified. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). All analyses were run stratified by menopausal status at recruitment and, additionally, by smoking status, alcohol intake, use of exogenous hormones and use of dietary supplements. In the multivariate analyses, dietary intake of beta-carotene, vitamin C and E was not associated with breast cancer risk in premenopausal [highest vs. lowest quintile: HR, 1.04 (95% CI, 0.85-1.27), 1.12 (0.92-1.36) and 1.11 (0.84-1.46), respectively] and postmenopausal women [0.93 (0.82-1.04), 0.98 (0.87-1.11) and 0.92 (0.77-1.11), respectively]. However, in postmenopausal women using exogenous hormones, high intake of beta-carotene [highest vs. lowest quintile; HR 0.79 (95% CI, 0.66-0.96), P (trend) 0.06] and vitamin C [0.88 (0.72-1.07), P (trend) 0.05] was associated with reduced breast cancer risk. In addition, dietary beta-carotene was associated with a decreased risk in postmenopausal women with high alcohol intake. Overall, dietary intake of beta-carotene, vitamin C and E was not related to breast cancer risk in neither pre- nor postmenopausal women. However, in subgroups of postmenopausal women, a weak protective effect between beta-carotene and vitamin E from food and breast cancer risk cannot be excluded.

Influence of education level on cancer survival in Sweden.

BACKGROUND: While cancer survival at several sites has historically been shown to vary by education level, a current comprehensive assessment of survival following a cancer diagnosis in Sweden, a country with universal health care and cancer screening, has yet to be carried out. METHODS: Using the 2006 update of the Swedish Family-Cancer Database and Cox's proportional hazards regression methods, we calculate the adjusted hazard ratio (HR) and 95% confidence interval to estimate the influence of education level on site-specific cancer survival. RESULTS: Significant positive associations between education level and cancer survival were observed following a diagnosis of upper aerodigestive track cancer, colon cancer, pancreatic cancer, lung cancer, kidney cancer, urinary bladder cancer, melanoma, non-Hodgkin's lymphoma, breast cancer, endometrial cancer, cervical cancer, prostate cancer, and testicular cancer. Although the HRs differed between cancer sites, compared with women and men completing <9 years of education, university graduates were associated with a significant 40% improved survival for all cancer sites combined. CONCLUSIONS: Survival differences by education level were observed for both indolent and aggressive malignancies.

Polymorphisms in the genes of the urokinase plasminogen activation system in relation to colorectal cancer.

BACKGROUND: Extracellular matrix degradation, mediated by the urokinase plasminogen activation (uPA) system, is a critical step in tumor invasion and metastasis. High tumor levels of uPA and its inhibitor PAI-1 have been correlated with poor cancer prognosis. We examined four single nucleotide polymorphisms (SNPs) with a potential effect on expression of genes in the uPA system for their role in colorectal cancer susceptibility and prognosis. PATIENTS AND METHODS: We genotyped the SNPs in 308 Swedish incident colorectal cancer patients with up to 16 years of follow-up and in 585 age- and sex-matched controls. We evaluated the associations between genotypes and colorectal cancer and Dukes' stage. Survival probabilities were compared between different subgroups. RESULTS: Patients with PAI-1 -675 5G/5G genotype had better survival than patients with 4G/4G or 4G/5G genotypes when they had Dukes' stage A or B tumors (P = 0.023 and P = 0.015, respectively). No statistically significant association was observed between the SNPs and the risk of colorectal cancer or Dukes' stage. CONCLUSIONS: Our results suggest a role for the PAI-1 genotype in colorectal cancer prognosis, but further studies are needed to evaluate the impact of our finding in the clinic.

Survival from invasive breast cancer among interval cases in the mammography screening programmes of northern Sweden.

The aim of this study was to estimate breast cancer survival according to detection mode for 5120 women with invasive breast cancer, in particular for those detected in the screening intervals. We found a significant survival difference in favour of women with cancer detected in the screening intervals (n=729) compared with those uninvited (n=1879) during the 13-year follow-up. Detection mode was proven to modify the prognostic effect of stage. Women with stage I interval cancer had shorter survival and those with stage II had longer survival than expected. It is suggested that interval cancers might consist of two subgroups with different behaviour: one of fast-growing tumours presenting as stage I cases and another of slow-growing tumours presenting as stage II+ cases. A hypothesis related to this observation is discussed.

A population-based seroepidemiological study of cervical cancer.

The epidemiology of cervical cancer indicates the presence of a sexually transmitted risk factor, attributable at least in part to infection with human papillomavirus (HPV) type 16 or 18. We performed a seroepidemiological study of HPV and cervical cancer in the counties of Västerbotten and Norrbotten in Northern Sweden, a low-risk area for cervical cancer. Sera from 94 cases of incident cervical cancer were matched against 188 age- and sex-matched controls derived from a population-based blood bank. IgG and IgA antibodies were measured against a panel of 12 antigens derived from HPV types 6, 11, 16, or 18, as well as against Herpes simplex virus type 1 and 2, Chlamydia trachomatis, cytomegalovirus, Epstein-Barr virus, and bovine papillomavirus. Significantly increased relative risks (RRs) were found for IgG to HPV 16- or 18-derived antigens from the L1 (RR = 3.1), E2 (RRs = 2.8 and 9.2), and E7 (RRs = 3.8 and 2.7) open reading frames and for IgA to HPV 16-derived antigens from the E2 (RR = 3.3) and E6 (RR = 2.7) open reading frames. The highest RR (9.2, confidence intervals 4.4-19.4) was associated with IgG to an HPV 18 E2 antigen. Antibodies against cytomegalovirus, Herpes simplex virus type 2, Epstein-Barr virus, or bovine papillomavirus were, on their own, not significantly associated with cervical cancer, but seropositivity against multiple infections was associated with a successively increased relative risk. An increased risk was also found for IgG to Chlamydia trachomatis (RR = 1.7, confidence interval = 1.0-2.7). The results indicate that several HPV antibodies are strongly associated with cervical cancer, providing further seroepidemiological support for an etiological role of HPV in cervical cancer.

Tumor necrosis factor a-11 and DR15-DQ6 (B*0602) haplotype increase the risk for cervical intraepithelial neoplasia in human papillomavirus 16 seropositive women in Northern Sweden.

HLA genes have been shown to be associated with cervical intraepithelial neoplasia (CIN), a precursor of cervical cancer. The human papillomaviruses (HPV) types 16 and 18 are the major environmental cause of this disease. Because the immune system plays an important role in the control of HPV infection, the association of polymorphic HLA could lead to a different immune response to control the development of cervical cancer. The aim of this study was to analyze the association between CIN and a microsatellite polymorphism of tumor necrosis factor (TNFa) taking HPV exposure and CIN-associated HLA haplotypes into account. In a nested case-control study in northern Sweden, 64 patients and 147 controls matched for age and sex and derived from the same population-based cohort were typed for TNFA, HLA-DR, and DQ and assayed for antibodies to HPV types 16 and 18. TNFa polymorphism was not associated with CIN per se. However, there was a significant increase in the frequency of TNFa-11 among HPV16-positive and HLA DR15-DQ6 (B*0602) patients compared with HPV16- and HLA-DQ6-negative patients (odds ratios, 5.4 and 9.3, respectively). The relative risk for CIN conferred by the combination of TNFa-11, HLA-DQ6, and HPV 16 positivity was 15. Our study suggests that the TNFa-11 allele is associated with HPV16 infection and associated with CIN in combination with HLA-DQ6 but not by itself.

Joint effects of different human papillomaviruses and Chlamydia trachomatis infections on risk of squamous cell carcinoma of the cervix uteri.

This case-control study based in Nordic serum banks evaluated the joint effects of infections with genital human papillomavirus (HPV) types, and Chlamydia trachomatis in the aetiology of cervical squamous cell carcinoma. Through a linkage with the cancer registries, 144 cases were identified and 420 controls matched to them. Exposure to past infections was defined by the presence of specific IgG antibodies. The odds ratio (OR) for the second-order interaction of HPV16, HPV6/11 and C. trachomatis was small (1.0) compared to the expected multiplicative OR, 57, and the additive OR, 11. The interactions were not materially different among HPV16 DNA-positive squamous cell carcinomas. When HPV16 was replaced with HPV18/33 in the analysis of second-order interactions with HPV6/11 and C. trachomatis, there was no evidence of interaction, the joint effect being close to the expected additive OR. Possible explanations for the observed antagonism include misclassification, selection bias or a true biological phenomenon with HPV6/11 and C. trachomatis exposures antagonizing the carcinogenic effects of HPV16.

MICA gene polymorphism and the risk to develop cervical intraepithelial neoplasia.

Cervical intraepithelial neoplasia (CIN) is associated with human papillomaviruses (HPV) and the HLA genes. The MICA (MHC class I chain-related gene A) is expressed by keratinocytes and epithelial cells and interacts with gamma delta T cells. It is therefore possible that MICA might influence the pathogenesis of CIN and cervical cancer through presentation of viral or tumor antigens. To investigate this, we determined the MICA transmembrane allele frequencies in a prospective population-based cohort study from the Västerbotten County in northern Sweden. 74 women developed CIN. 153 control women who remained healthy during follow up were matched for age. Five polymorphic microsatellite alleles of MICA were identified by a polymerase chain reaction-based (PCR) technique using fluorescent-labeled primers. MICA A5 and A5.1 were the most common alleles in this population. None of the alleles of MICA were associated with disease. The frequency of MICA allele A5 was higher among HPV 18 seropositive than HPV 18 seronegative patients but this difference was not significant after the correction of p value. In conclusion, microsatellite allele polymorphism of MICA transmembrane part is not associated with cervical intraepithelial neoplasia.

Tumor necrosis factor A and MHC class I chain related gene A (MIC-A) polymorphisms in Swedish patients with cervical cancer.

Human papillomaviruses type 16 and 18 are the major cause of cervical cancer. However, genetic factors contribute to the propensity of persistent HPV infection and cervical carcinoma. Allelic variants of the human leukocyte genes have shown to be associated with cervical neoplasia. The strongest associations have been found with the genes in the HLA class II region. The aim of this study was to analyze the association of two non-HLA class II markers with invasive cervical cancer. Microsatellite polymorphism of the TNFA gene located in the class III region and a short tandem repeat polymorphism of the MICA gene located in the centromeric end of the HLA class I region were analyzed. Eighty-five patients and 120 matched control individuals from a population-based cohort from Northern Sweden participated in this nested case-control study. MICA was not associated with cervical carcinoma. TNFa-11 frequency was increased in the HPV18 DNA positive patients (OR = 2.84, p = 0.0481, CI = 1.04-7.78, pc = NS). TNFa-11 was not associated with susceptibility to HPV16 infection, but it increased the risk for cervical cancer with the HLA DQ6 (DQA 1*0102-DQB 1*0602) haplotype. Our findings indicate that the association of TNFA with cervical cancer is different with CIN. The extended HLA DQ6-TNFa-11 haplotype is increasing the risk for development of cervical cancer significantly (OR = 3.08, p = 0.0104, CI = 1.30-7.31).

Body mass index, circulating levels of sex-steroid hormones, IGF-I and IGF-binding protein-3: a cross-sectional study in healthy women.

OBJECTIVE: Excess weight has been associated with increased risk of cancer at several organ sites. In part, this effect may be modulated through alterations in the metabolism of sex steroids and IGF-I related peptides. The objectives of the study were to examine the association of body mass index (BMI) with circulating androgens (testosterone, androstenedione and dehydroepiandrosterone sulfate (DHEAS)), estrogens (estrone and estradiol), sex hormone-binding globulin (SHBG), IGF-I and IGF-binding protein (IGFBP)-3, and the relationship between sex steroids, IGF-I and IGFBP-3. DESIGN AND METHODS: A cross-sectional analysis was performed using hormonal and questionnaire data of 620 healthy women (177 pre- and 443 post-menopausal). The laboratory measurements of the hormones of interest were available from two previous case-control studies on endogenous hormones and cancer risk. RESULTS: In the pre-menopausal group, BMI was not related to androgens and IGF-I. In the post-menopausal group, estrogens, testosterone and androstenedione increased with increasing BMI. The association with IGF-I was non-linear, with the highest mean concentrations observed in women with BMI between 24 and 25. In both pre- and post-menopausal subjects, IGFBP-3 did not vary across BMI categories and SHBG decreased with increasing BMI. As for the correlations between peptide and steroid hormones, in the post-menopausal group, IGF-I was positively related to androgens, inversely correlated with SHBG, and not correlated with estrogens. In the pre-menopausal group, similar but weaker correlations between IGF-I and androgens were observed. CONCLUSIONS: These observations offer evidence that obesity may influence the levels of endogenous sex-steroid and IGF-related hormones in the circulation, especially after menopause. Circulating IGF-I, androgens and SHBG appear to be related to each other in post-menopausal women.

Patient with B-cell neoplasia (immunoblastic sarcoma) and the Philadelphia chromosome.

Philadelphia chromosome-positive cells with a standard translocation (9;22) were found in bone marrow and peripheral blood samples from a patient with non-Hodgkin's lymphoma (immunoblastic sarcoma) in the final leukemic phase. The neoplastic clone was of monoclonal B-cell character with surface Ig (mu, kappa) and mouse red blood cell receptors. This is the first case with surface Ig and t(9;22) cells reported without evidence of chronic myeloid leukemia. Also, additional consistent chromosome aberrations were found.

Treatment of Hodgkin's disease: the Swedish National Care Programme experience.

Since 1985 a Swedish National Care Programme has provided tailored principles for the diagnosis, staging, treatment and follow-up of patients with Hodgkin's disease (HD). This report gives the rationale behind the recommendations and presents treatment results for 648 patients diagnosed between 1985 and 1989 after a median follow-up of 70 months. Two hundred and twenty-nine (35%) patients were over 60 years of age. Treatment results for patients below 60 years of age in early and intermediate stages were favourable, provided the recommendations were followed. In advanced stages, the outcome was inferior in patients with CS IIB bulky disease and stage IVB. The prognosis of elderly patients remains poor, although it is too early to evaluate any impact of revisions made in 1989. The tailored principles, which usually entail less staging and/or treatment than is generally the case in the early and intermediate stages, produced favourable results when applied to an unselected group of patients with HD. Only minor changes were made in the recommendations during the 1994 revision.

Early breast cancer deaths in women aged 40-74 years diagnosed during the first 5 years of organised mammography service screening in north Sweden.

The aim of this study was to analyse individual cases of lethal breast cancer and not to evaluate the screening programme. Women aged 40-74 years who were diagnosed with breast cancer in 1990-94 and died on or before 31 December 1998, during the gradual introduction of organised mammography service screening in north Sweden, were included in the study. Out of 342 breast cancer deaths, 280 (82%) were in symptomatic patients whose cancers were clinically detected. Most breast cancers that proved fatal were already in an advanced stage and/or of high histological grade at the time of detection. A shift towards a lower stage was seen among screen-detected and interval-detected fatal cases. In a few of the cases with fatal outcome, in patients primarily presenting with histological grade I tumours of various sizes or small screen-detected tumours less than 10mm in size, early diagnosis by mammography followed by state-of-the-art treatment did not seem to have been enough to prevent death.

Service screening with mammography. Long-term effects on breast cancer mortality in the county of Gävleborg, Sweden.

In the current study the long-term effects of a pilot service screening programme in the Swedish county of Gävleborg were studied. Women aged 40-64 years in 13 sub-areas were followed from start of screening between 1974 and 1979. Two control groups were used for comparison; the neighbouring counties and all of Sweden. A reference period prior to the study period was used to facilitate an adjustment for possible differences in baseline breast cancer mortality. Only deaths from breast cancer diagnosed after the first invitation to screening were analysed. Two outcome measures were used for breast cancer mortality; the underlying cause of death and excess mortality. Using the neighbouring counties as a control group, the relative risk, after 22 years of follow-up, of 10 years of screening was estimated at 0.84 (95% CI 0.71-1.00) using excess mortality. Due to lead time bias the relative risk was overestimated by 4%. Hence, a significant 20% reduction of breast cancer excess mortality was found.

Excess mortality from breast cancer in relation to mammography screening in northern Sweden.

OBJECTIVES: Previous randomised studies of mammography screening have shown a significant effect on breast cancer mortality, particularly in women aged 50-69 at randomisation. Breast cancer mortality has traditionally been studied by judgments on causes of death, either from cause of death registers or from medical records. In this study an alternative method was used, estimating the excess mortality associated with breast cancer. SETTING: In 1990 two counties of northern Sweden started population based mammography screening of women aged 40-74. The unscreened population in the two other counties of the same region were selected as controls. RESULTS: Excess mortality associated with breast cancer was lower in the screened population, and was discernible three to four years after the start of screening. The relative risk estimate, based on the cumulative excess number of deaths from breast cancer during 1990-95 in the screened versus the control population aged 40-74 (at diagnosis of breast cancer), was 0.72 (95% confidence interval (CI) 0.53 to 0.99). For women aged 50-69 it was 0.67 (95% CI 0.46 to 0.99). In the 50-69 age group the estimated excess number of deaths from breast cancer during 1995 was 17.0 per 100,000 women (95% CI 5.0 to 29.0) in the screened counties and 51.1 per 100,000 (95% CI 30.2 to 71.9) in the unscreened counties. CONCLUSIONS: Population based routine screening has substantial effects on breast cancer mortality in women aged 50-69. Estimation of excess mortality can be used in future studies to evaluate the effects of mammography screening on breast cancer mortality.

Service screening with mammography of women aged 50-69 years in Sweden: effects on mortality from breast cancer.

OBJECTIVES: To estimate the effect of the population based service screening programme in Sweden on mortality from breast cancer among women aged 50-69. SETTING; In 1986, population based service screening with mammography started in Sweden, and by 1997 screening had been introduced in all counties. Half of the counties invite women from 40 years of age whereas women 50 and older are invited in the other counties. The upper age limit was either 69 or 74. Women in the age group 50-69 years are thus invited to screening in all counties. METHODS: The counties which started with mammographic screening in 1986-87 constituted the study group and were compared with the counties which started in 1993 or later. In 1987 the mean number of women aged 50-69 was 161,986 and 98,608 in the study and control groups, respectively. Refined excess mortality (smoothed with the Lowess method) from breast cancer and refined cause specific mortality from breast cancer were used as effect measures. To adjust for geographical differences in mortality from breast cancer a reference period was used. Allowance was made for two potential biases: (a) inclusion bias implying the inclusion of cases diagnosed before invitation to screening in the first screening round, and (b) lead time bias. RESULTS: After a mean follow up time of 10.6 years since the start of screening and a mean individual follow up time of 8.4 years, a non-significant reduction in refined excess mortality for breast cancer was estimated as relative risk (RR) 0.84 (95% confidence interval (95% CI) 0.67 to 1.05). After adjustment for inclusion and lead time biases the RR was 0.80 (20% reduction). Only 27% of the deaths from breast cancer in the total mortality for women aged 50-79 at death consisted of women aged 50-69 at diagnosis who were diagnosed after the start of screening. This figure has important implications for judgement of the impact of screening on age specific national breast cancer mortalities. CONCLUSIONS: A non-significant reduction in mortality from breast cancer was found in counties performing service screening with mammography in Sweden. Adjustment for possible biases changed the result towards a larger effect of screening. The results do not contradict the effects found in the Swedish randomised mammography trials.

Women with false positive screening mammograms: how do they cope?

OBJECTIVES: To assess the long term psychological impact on women who were recalled for further investigation after mammography screening and to find any factors that might predict coping ability in order to identify those subjects who require additional support at an earlier stage. SETTING: Counties of Västerbotten and Västernorrland, Sweden. METHODS: A prospective design was used in which 252 recalled women completed questionnaires twice--once within a week of having received the all-clear and again at follow up six months later. A group of 1104 randomly selected, screen negative women were followed up in the same way for comparison. The questionnaire included the Psychological Consequences Questionnaire (PCQ) and basic sociodemographic data. The main outcome measure was the total score on the PCQ at six months. RESULTS: Of the 252 women, 235 (93%) completed both questionnaires. In the control group, 987 (89.4%) women responded. Six months after the all-clear, recalled women were still significantly more anxious (p < 0.001) than those who had been screened but not recalled. The strongest predictor of psychological distress at six months was the PCQ score at the first measurement. Other predictors were a low level of education, living in high density urban areas, and having only one child or no children at all. Widows appeared to cope better than other women. CONCLUSIONS: It is possible to define a group of women with false positive results who are already at risk of coping less effectively at the time of recall. Offering these women counselling or other types of support should be considered.