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Biomedical subjects

E Pukkala

Publications and source records attributed to E Pukkala.

At least 19 recordsLinked to original sources
PubMed2003

Does yttrium radiosynovectomy increase the risk of cancer in patients with rheumatoid arthritis?

OBJECTIVE: To study the long term risk of cancer in patients with rheumatoid arthritis (RA) who have been treated with yttrium. METHODS: The medical record numbers of 1228 patients with RA who were admitted to hospital in 1979-85 were identified in the database of Jyväskylä Central Hospital. Radiosynovectomy of the knee joint was performed in a total of 143 patients using yttrium-90 silicate during the years 1970-85, while 1075 did not receive yttrium radiosynovectomy; 10 received yttrium treatment later than 1985 and were excluded from the analysis. The Finnish Cancer Registry database was used to examine whether the subjects had cancer during the follow up from 1979 until the end of 1999. RESULTS: Nine cases of cancer were found among the patients who had received yttrium, whereas the expected number based on the incidence among the population in the region was 14.9. The standardised incidence ratio of cancer was 0.6 (95% confidence interval (CI) 0.3 to 1.1) for the patients who received yttrium, and 1.1 (95% CI 0.9 to 1.3) for the patients who did not receive yttrium. CONCLUSIONS: Yttrium treatment did not increase the risk of cancer.

Adult↗
PubMed2003

Lung cancer after treatment for Hodgkin's disease: focus on radiation effects.

Aspects of radiation-induced lung cancer were evaluated in an international study of Hodgkin's disease. The study population consisted of 227 patients with lung cancer and 455 matched controls. Unique features included dose determinations to the specific location in the lung where each cancer developed and quantitative data on both chemotherapy and tobacco use obtained from medical records. The estimated excess relative risk (ERR) per Gy was 0.15 (95% CI: 0.06-0.39), and there was little evidence of departure from linearity even though lung doses for the majority of Hodgkin's disease patients treated with radiotherapy exceeded 30 Gy. The interaction of radiation and chemotherapy that included alkylating agents was almost exactly additive, and a multiplicative relationship could be rejected (P = 0.017). Conversely, the interaction of radiation and smoking was consistent with a multiplicative relationship, but not with an additive relationship (P < 0.001). The ERR/Gy for males was about four times that for females, although the difference was not statistically significant. There was little evidence of modification of the ERR/Gy by time since exposure (after a 5-year minimum latent period), age at exposure, or attained age. Because of the very high radiation doses received by Hodgkin's disease patients and the immunodeficiency inherent to this lymphoma and that associated with chemotherapy, generalizing these findings to other populations receiving considerably lower doses of radiation should be done cautiously.

Adult↗
PubMed2002

Human papillomavirus infection as a risk factor for anal and perianal skin cancer in a prospective study.

Human papillomavirus has emerged as the leading infectious cause of cervical and other anogenital cancers. We have studied the relation between human papillomavirus infection and the subsequent risk of anal and perianal skin cancer. A case-cohort study within two large Nordic serum banks to which about 760 000 individuals had donated serum samples was performed. Subjects who developed anal and perianal skin cancer during follow up (median time of 10 years) were identified by registry linkage with the nationwide cancer registries in Finland and Norway. Twenty-eight cases and 1500 controls were analysed for the presence of IgG antibodies to HPV 16, 18, 33 or 73, and odds ratios of developing anal and perianal skin cancer were calculated. There was an increased risk of developing anal and perianal skin cancer among subjects seropositive for HPV 16 (OR=3.0; 95%CI=1.1-8.2) and HPV 18 (OR=4.4; 95%CI=1.1-17). The highest risks were seen for HPV 16 seropositive patients above the age of 45 years at serum sampling and for patients with a lag time of less than 10 years. This study provides prospective epidemiological evidence of an association between infection with HPV 16 and 18 and anal and perianal skin cancer.

Adult↗
PubMed2002

Malignant skin cancers in the Finnish Twin Cohort: a population-based study, 1976-97.

BACKGROUND: Both hereditary and environmental factors are implicated in the aetiology of cutaneous neoplasms. Studies of twins make it possible to estimate the contribution of inherited genes to the development of disease. OBJECTIVE: To assess the importance of hereditary and environmental factors (including physical environment and lifestyles) in malignant melanoma and malignant nonmelanoma of the skin. METHODS: The Finnish Twin Cohort, comprising 25 882 adult like-sexed twins with established zygosity, was linked with the Finnish Cancer Registry to identify malignant skin cancers in a prospective follow-up from 1976 to 1997. Standardized incidence ratios were computed based on national rates. RESULTS: Sixty twins were diagnosed with melanoma and 49 twins with nonmelanoma during the follow-up. The risks of these cancers did not differ from the risk in the population at large. There was only one pair where both twins had a malignant skin cancer (dizygotic male twins both with squamous cell carcinoma). CONCLUSIONS: The near-total lack of concordance for skin cancer in twin pairs suggests that environmental and not hereditary effects are most important in the causation of malignant skin cancers in a white population with low levels of sun exposure.

Adolescent↗
PubMed2002

Cancer at sea: a case-control study among male Finnish seafarers.

AIMS: To study the possible work related reasons for the increased incidence of many cancers among seafarers. METHODS: A case-control study, nested in a cohort of all male seafarers (n = 30 940) who, according to the files of the Seamen's Pension Fund, had worked on board Finnish ships for any time during the period 1960-80. Cases of cancer of the lung, nervous system, kidney, and pancreas, leukaemia, lymphoma, and all cases histologically defined as mesotheliomas were identified from the Finnish Cancer Registry in 1967-92. The preceding numbers of years at sea in various occupational categories were collected according to the type of ship (dry cargo ship, tanker, passenger vessel, icebreaker, other vessel). RESULTS: The incidence for lung cancer among engine crew increased with the increase in employment time, the odds ratio (OR) after three years being 1.68 (95% CI 1.17 to 2.41). The OR of lung cancer for deck officers was 0.42 (95% CI 0.29 to 0.61). Deck personnel on icebreakers had a significantly increased risk of lung cancer > or =20 years after first employment (OR 3.41, 95% CI 1.23 to 9.49). The OR for mesothelioma among engine crew with a latency of 20 years was 9.75 (95% CI 1.88 to 50.6). The OR for renal cancer among deck officers after three years employment was 2.15 (95% CI 1.14 to 4.08), but there was no increase by employment time or by latency. A rise of OR for lymphoma was detected among deck personnel on tankers, if the employment had lasted over three years (OR 2.78, 95% CI 0.98 to 7.92). The risk pattern for leukaemia was similar to that of lymphoma, the OR among deck personnel on tankers varying from 2.26 (95% CI 1.01 to 5.06) to 6.86 (95% CI 1.62 to 28.8) depending on the length of employment. CONCLUSIONS: Results indicate that occupational exposures of deck crews on tankers add to their risk of renal cancer, leukaemia, and possibly lymphoma. Engine crews have an asbestos related risk of mesothelioma, and the engine room conditions also seem to increase risk of lung cancer.

Adult↗
PubMed2001

Survival of breast cancer patients in BRCA1, BRCA2, and non-BRCA1/2 breast cancer families: a relative survival analysis from Finland.

Reports on the prognosis of familial breast cancer patients have been contradictory. True differences in survival, if they exist, would have important implications for genetic counselling and in treatment of hereditary breast cancer. We assessed the survival rates of 359 familial breast cancer patients (32 patients from BRCA1-positive families, 43 patients from BRCA2-positive families and 284 patients from BRCA1/2-negative breast cancer families) and compared them with those of all other breast cancer patients diagnosed in Finland from 1953 to 1995 (n = 59,517). Cumulative relative survival rates (RSR) were calculated by dividing the observed survival rates by the expected ones. The expected survival rates were derived from the sex, age and calendar year specific life-tables of the general population in Finland. Regression model was used to calculate relative excess risk of death (RR) and to adjust for confounding factors. The overall 5-year RSR of the patients in the BRCA1 families, BRCA2 families, non-BRCA1/2 families and among sporadic cases was 67%, 77%, 86% and 78%, respectively. However, we found no significant differences in the RR adjusted for age, stage and year of diagnosis between the different familial patient groups or the general breast cancer population. In the BRCA1 families the RR tended to be higher [RR 1.30, 95% confidence interval (CI) 0.63--2.70] and in the BRCA2 families lower (RR 0.78, 95% CI 0.39--1.57) than among the general breast cancer patient population. The RR among patients in the non-BRCA1/2 families did not differ from that of the general patient population.

Adolescent↗
PubMed2001

Incidence of Hodgkin's disease in Nordic countries.

We analysed age and sex-specific trends in the incidence of Hodgkin's lymphoma in Denmark, Sweden, Norway, and Finland during 1978-97. The incidence of Hodgkin's lymphoma decreased significantly in all age groups above 40 years; there was a significant increase in incidence among adolescents and young adults. This increase occurred primarily for Hodgkin's lymphoma of the nodular sclerosis subtype. These observations emphasise the need to identify risk factors for Hodgkin's lymphoma in the young.

Adolescent↗
PubMed2001

Human papillomavirus infection as a risk factor for squamous-cell carcinoma of the head and neck.

BACKGROUND: Oncogenic human papillomaviruses (HPVs), especially HPV type 16 (HPV-16), cause anogenital epithelial cancers and are suspected of causing epithelial cancers of the head and neck. METHODS: To examine the relation between head and neck cancers and HPVs, we performed a nested case-control study within a joint Nordic cohort in which serum samples were collected from almost 900,000 subjects. Samples collected at enrollment from 292 persons in whom squamous-cell carcinoma of the head and neck developed, on average, 9.4 years after enrollment and from 1568 matched controls were analyzed for antibodies against HPV-16, HPV-18, HPV-33, and HPV-73 and for cotinine levels as a marker of smoking habits. Polymerase-chain-reaction (PCR) analyses for HPV DNA were performed in tumor tissue from 160 of the study patients with cancer. RESULTS: After adjustment for cotinine levels, the odds ratio for squamous-cell carcinoma of the head and neck in subjects who were seropositive for HPV-16 was 2.2 (95 percent confidence interval, 1.4 to 3.4). No increased risk was observed for other HPV types. Fifty percent of oropharyngeal and 14 percent of tongue cancers contained HPV-16 DNA, according to PCR analysis. CONCLUSIONS: HPV-16 infection may be a risk factor for squamous-cell carcinoma of the head and neck.

Adult↗
PubMed2001

Inherited susceptibility to uterine leiomyomas and renal cell cancer.

Herein we report the clinical, histopathological, and molecular features of a cancer syndrome with predisposition to uterine leiomyomas and papillary renal cell carcinoma. The studied kindred included 11 family members with uterine leiomyomas and two with uterine leiomyosarcoma. Seven individuals had a history of cutaneous nodules, two of which were confirmed to be cutaneous leiomyomatosis. The four kidney cancer cases occurred in young (33- to 48-year-old) females and displayed a unique natural history. All these kidney cancers displayed a distinct papillary histology and presented as unilateral solitary lesions that had metastasized at the time of diagnosis. Genetic-marker analysis mapped the predisposition gene to chromosome 1q. Losses of the normal chromosome 1q were observed in tumors that had occurred in the kindred, including a uterine leiomyoma. Moreover, the observed histological features were used as a tool to diagnose a second kindred displaying the phenotype. We have shown that predisposition to uterine leiomyomas and papillary renal cell cancer can be inherited dominantly through the hereditary leiomyomatosis and renal cell cancer (HLRCC) gene. The HLRCC gene maps to chromosome 1q and is likely to be a tumor suppressor. Clinical, histopathological, and molecular tools are now available for accurate detection and diagnosis of this cancer syndrome.

Adult↗
PubMed2001

Frequency of specific cancer types in dermatomyositis and polymyositis: a population-based study.

BACKGROUND: Dermatomyositis and polymyositis are associated with cancer, but previous nationwide studies have not had sufficient cases to test the association between myositis and specific cancer types. Our aim was to investigate the risk of specific cancer types in individuals with dermatomyositis and polymyositis. METHODS: We did a pooled analysis of published national data from Sweden, Denmark, and Finland. All patients with dermatomyositis and polymyositis (> or =15 years old) were identified by discharge diagnosis from the Swedish National Board of Health (1964-83), Danish Hospital Discharge Registry (1977-89), and Finnish National Board of Health (1969-85). Personal details were matched to national cancer registries, to identify all cases of cancer up to 1987 in Sweden, 1995 in Denmark, and 1997 in Finland, and to national death registries for the same periods. We calculated standardised incidence ratios (SIR) for individual cancer sites for dermatomyositis and polymyositis separately, using national cancer rates by country, sex, age, and date. FINDINGS: We identified 618 cases of dermatomyositis, of whom 198 had cancer. 115 of the 198 developed cancer after diagnosis of dermatomyositis. This disease was strongly associated with malignant disease (SIR 3.0, 95% CI 2.5-3.6), particularly ovarian (10.5, 6.1-18.1), lung (5.9, 3.7-9.2), pancreatic (3.8, 1.6-9.0), stomach (3.5, 1.7-7.3), and colorectal (2.5, 1.4-4.4) cancers, and non-Hodgkin lymphoma (3.6, 1.2-11.1). 137 of the 914 cases of polymyositis had cancer, which developed after diagnosis of polymyositis in 95. Polymyositis was associated with a raised risk of non-Hodgkin lymphoma (3.7, 1.7-8.2), and lung (2.8, 1.8-4.4) and bladder cancers (2.4, 1.3-4.7). In both dermatomyositis and polymyositis, risk of malignant disease was highest at time of myositis diagnosis. INTERPRETATION: Our results provide evidence that dermatomyositis is strongly associated with a wide range of cancers. The overall risk of malignant disease is also modestly increased among patients with polymyositis, with an excess for some cancers.

Dermatomyositis↗
PubMed2001

Serotypes of Chlamydia trachomatis and risk for development of cervical squamous cell carcinoma.

CONTEXT: Human papillomavirus (HPV) infection has been established as a cause of cervical cancer. Epidemiologic studies suggest that Chlamydia trachomatis infection also confers increased risk for cervical squamous cell carcinoma (SCC). Whether this risk is serotype-specific is unknown. OBJECTIVE: To study the association between exposure to different C trachomatis serotypes and subsequent development of cervical SCC. DESIGN AND SETTING: Longitudinal, nested case-control study within a cohort of 530 000 women who provided samples to serum banks in Finland, Norway, and Sweden. The data files were linked to respective national cancer registries. SUBJECTS: One hundred twenty-eight women who had developed invasive cervical SCC at least 12 months following serum donation. Each case had 3 matched controls. MAIN OUTCOME MEASURE: Risk for the development of cervical SCC by IgG antibodies to 10 different C trachomatis serotypes, adjusted for antibodies to HPV types 16, 18, and 33 and for serum cotinine levels. RESULTS: Of specific C trachomatis serotypes, serotype G was most strongly associated with SCC (adjusted odds ratio [OR], 6.6; 95% confidence interval [CI], 1. 6-27.0). Other serotypes associated with SCC were I (OR, 3.8; 95% CI, 1.3-11.0) and D (OR, 2.7; 95% CI, 1.3-5.6). Presence of serum IgG antibodies to more than 1 serotype increased the adjusted ORs for SCC (P<.001 for trend). CONCLUSIONS: Chlamydia trachomatis serotype G is most strongly associated with subsequent development of cervical SCC. Increasing numbers of exposures to different C trachomatis serotypes also increases risk. Our results strengthen the evidence that there is a link between past C trachomatis infection and cervical SCC.

Antibodies, Bacterial↗
PubMed2001

Incidence of cancer among persons with schizophrenia and their relatives.

BACKGROUND: It has repeatedly been reported that the risk for cancer in patients with schizophrenia is different from that of the general population, specifically a lower risk for lung cancer despite increased smoking. Confirmation of these associations could lead to hypotheses on shared risk or protective factors, either genetic or environmental. METHODS: From Finland's National Hospital Discharge and Disability Pension registers, Helsinki, we identified a cohort of 26 996 individuals born between 1940 and 1969 and treated for schizophrenia between 1969 and 1991. They were followed up for cancer from 1971 to 1996 by record linkage with the Finnish Cancer Registry, yielding 446 653 person-years at risk, and standardized incidence ratios (SIRs) were calculated. Likewise, 39 131 parents and 52 976 siblings of the patients with schizophrenia were followed up to explore familial genetic hypotheses on deviations in cancer risk. RESULTS: In patients with schizophrenia, an increased overall cancer risk was found (724 cases observed vs 619 expected; SIR, 1.17; 95% confidence interval [CI], 1.09-1.25). Half of the excess cases were attributable to lung cancer (SIR, 2.17; 95% CI, 1.78-2.60), and the strongest relative increase in risk was in pharyngeal cancer (SIR, 2.60; 95% CI, 1.25-4.77). Cancer incidence in siblings (SIR, 0.89; 95% CI, 0.83-0.94) and parents (SIR, 0.91; 95% CI, 0.89-0.93) was consistently lower than that in the general population. CONCLUSION: Although specific lifestyle factors, particularly tobacco smoking and alcohol consumption, probably account for the increased cancer risk in patients with schizophrenia, the decreased risk in relatives would be compatible with a postulated genetic risk factor for schizophrenia offering selective advantage to unaffected relatives.

Alcohol Drinking↗
PubMed2001

Occupational exposures and cancers of the endometrium and cervix uteri in Finland.

BACKGROUND: Endometrial cancer incidence rates are low in Asia and Africa and high in North America and Northern Europe. Cervical cancer is often the most common female cancer in developing countries, and infection with human papillomavirus (HPV) is its main risk factor. However, other factors, such as occupational exposures may modify the HPV-related risk. We conducted an exploratory register-linkage study in Finland to assess the role of occupational exposures on incidence rates of cancers of the endometrium and cervix uteri. METHODS: Occupational risk factors for endometrial and cervical cancers were explored in a 25-year follow-up of female workers born 1906-1945 (N = 413,877) identified through the Population Census of Finland of 1970. Job titles in census records were converted to exposures of 31 occupational agents through a job-exposure matrix. Poisson regression models estimated relative risks (RR) for each agent, standardized for birth cohort, follow-up period, and socio-economic status. For each agent, the product of level and probability of exposure was calculated and subdivided in three categories: zero, low, and medium/high. Adjustment at the job title level was done for the turnover rate (endometrial and cervical cancers), mean parity, and age at first birth (endometrial cancer). RESULTS: Endometrial cancer (2,833 cases) was associated with exposure to animal dust (RR 1.2, low level, 174 cases) and sedentary work (RR 1.3, high level, 145 cases). Cervical cancer (1,101 cases) was associated with exposure to aliphatic and alicyclic (RR 1.3, low level, 91 cases), aromatic (RR 1.2, low level, 318 cases; RR 1.4, high level, 41 cases), and chlorinated hydrocarbon solvents (RR 1.3, low level, 50 cases), silica dust (RR 1.2, low level, 251 cases), and wood dust (RR 1.2, low level, 249 cases). CONCLUSIONS: This study suggests that occupational exposures may be associated with increased risk of endometrial and cervical cancers.

Adult↗
PubMed2001

Familial cutaneous leiomyomatosis is a two-hit condition associated with renal cell cancer of characteristic histopathology.

Little has been known about the molecular background of familial multiple cutaneous leiomyomatosis (MCL). We report here a clinical, histopathological, and molecular study of a multiple cutaneous leiomyomatosis kindred with seven affected members. This detailed study revealed strong features of a recently described cancer predisposition syndrome, hereditary leiomyomatosis and renal cell cancer (HLRCC). The family was compatible with linkage to the HLRCC locus in 1q. Also, all seven cutaneous leiomyomas derived from the proband and analyzed for loss of heterozygosity displayed loss of the wild-type allele, confirming the association with a susceptibility gene in chromosome 1q. One individual had had renal cell cancer at the age of 35 years. This tumor displayed a rare papillary histopathology, which appears to be characteristic for HLRCC. The derived linkage, loss of heterozygosity, and clinical data suggest that MCL and HLRCC are a single disease with a variable phenotype. The possibility that members of leiomyomatosis families are predisposed to renal cell cancer should be taken into account.

Adult↗
PubMed2001

Risk of a new primary cancer among patients with lung cancer of different histological types.

The risk of a new primary cancer (NPC) among 77548 Finnish lung cancer patients from 1953 to 1995 was analysed by the histological type of the lung cancer. The relative risks were expressed as standardised incidence ratios (SIR, ratio of the observed and expected numbers of cases). During the follow-up, 1148 NPCs were observed among men and 152 among women. After exclusion of lung cancers, the risk of NPC was elevated in both males (SIR 1.07; 95% confidence interval (CI) 1.00-1.14) and females (SIR 1.21; 95% CI 1.02-1.42). The excess was larger among lung cancer patients with small-cell carcinoma and adenocarcinoma than those with squamous-cell carcinoma. In all major histological groups of lung cancer, significant excess risks were found for cancers of the larynx (SIRs 2.94-4.25), and bladder (SIRs 2.16-2.86). Significantly elevated SIRs were also found for cancers of the stomach (SIR 1.42; 95% CI 1.12-1.76) and kidney (SIR 2.18; 95% CI 1.56-2.97) in squamous-cell carcinoma; for brain tumours (SIR 3.26; 95% CI 1.20-7.09) in small-cell carcinoma; and for cancers of the prostate (SIR 1.68; 95% CI 1.21-2.27) and thyroid (SIR 3.79; 95% CI 1.23-8.85), and brain tumours (SIR 2.34; 95% CI 1.07-4.43) in adenocarcinoma. The risk of contracting NPC at sites where the majority of tumours are adenocarcinomas was elevated among patients with adenocarcinoma of the lung, but not among squamous-cell or small-cell carcinoma patients. In adenocarcinoma, the excess risks of several smoking-related cancers tended to be somewhat lower than those in the other two histological categories. The relative risk of a NPC among patients diagnosed with lung cancer in 1985-1995 was higher than that of patients from earlier periods in all comparable follow-up categories (up to 10 years), possibly suggesting that the increased use of cytostatic drugs had increased the risk of NPC.

Adenocarcinoma↗
PubMed2001

Incidence of cancer among women using long versus monthly cycle hormonal replacement therapy, Finland 1994-1997.

OBJECTIVE: This study was initiated as a consequence of a clinical observation in one hospital of several endometrial carcinomas among users of a fixed combination of a 3-month cycle oral hormonal replacement therapy (HRT), which has been marketed in Finland since 1990. We studied whether the use of 3-month ("long") cycle HRT is accompanied by a higher risk of endometrial cancer than the use of monthly cycle HRT. METHODS: A nationwide cohort of 15,956 long cycle and 78,549 monthly cycle HRT users since January 1994 was extracted from the files of the national medical reimbursement register and followed up for cancer incidence through the Finnish Cancer Registry up to the end of 1997. RESULTS: There were 61 cases of endometrial cancer among long cycle HRT users which significantly exceeds the average incidence in the Finnish population (standardized incidence ratio (SIRlong) 2.0, 95% confidence interval (CI) 1.6-2.6). The SIR among users of monthly cycle HRT products (SIRmonthly) was 1.3 (1.1-1.6) and the ratio SIRlong/SIRmonthly thus 1.5 (95% CI 1.1-2.1). Endometrial cancers among long cycle HRT users occur more often in early stages than in the general population and are more often highly differentiated. A survey of a sample of endometrial cancer patients in the long cycle HRT group revealed that all of them also had a history of other HRT. Users of both long and monthly cycle HRT had a similar statistically significant 30% excess of breast cancer in comparison to national incidence rates, while the incidence of colon cancer was decreased in both groups. There was no difference between the HRT groups in overall cancer morbidity. CONCLUSIONS: Our results imply that all HRT users have an increased risk of endometrial cancer, and long cycle HRT carries a higher relative risk than monthly cycle HRT. However, in this non-randomized setting it is impossible to judge whether this excess is attributable to the type of HRT or to patient selection. In-depth studies are needed to find out possible dose-response associations and to evaluate the role of potential confounders in detail.

Adenocarcinoma↗
PubMed2001

Grand multiparity and the risk of breast cancer: population-based study in Finland.

OBJECTIVES: The significance of reproductive factors on breast cancer risk has so far been characterized in populations with 5-paras as the highest category of parity. We extended these studies to a nationwide cohort of women with at least five births (grand multiparas = GM) by assessing the significance of parity, age at first birth, and average birth interval to the risk of breast cancer. METHODS: The study cohort obtained from the Population Register of Finland comprised 86,978 GM-women; the incidence of cancer cases was obtained from the populated-based Finnish Cancer Registry. During a follow-up of about 2 million person-years, 1508 breast cancers were obtained. Standardized incidence ratios (SIRs) were calculated by dividing the number of observed cases by the number expected on the basis of national rates. RESULTS: In the GM cohort the incidence of breast cancer was low (SIR 0.55, 95% confidence interval 0.52-0.58). The relative risk decreased significantly from 5-paras (SIR 0.60, adjusted for the other study variables) to 8-paras (SIR 0.40). The increase in the age at first birth from less than 20 years to 30+ years nearly doubled the risk (SIR from 0.40 to 0.73). Parity was a significant risk determinant only in ductal cancer, while shortening the birth interval was protective only in lobular cancer. The incidence of advanced breast cancer among GM-women exceeded the population rate in premenopausal women and in women with first birth at the age of 30 years or more. CONCLUSIONS: Our study demonstrated that young age at first birth and increasing number of births were independent and powerful protective factors from the fifth child onwards, while birth interval was weak in this respect. The tumor morphology and the clinical advancement of malignancy modified the dependence of breast cancer risk on reproductive variables.

Aged↗