Risk for contralateral breast cancers in a population covered by mammography: effects of family history,age at diagnosis and histology

Background Improved survival for breast cancer is increasing the likelihood of contralateral tumors. Mammographic screening is partially contributing to the survival advantage, while changing many aspects of breast cancer presentation, including age at diagnosis, histology and familial risk. As mammography has become widely used, it is important to quantify the risks for contralateral breast cancer in a population with a national access to mammographic screening service. Methods The nation-wide Swedish Family-Cancer Database was used to calculate risks for contralateral breast cancer between years 1990 (1993) and 2002. The standardized incidence ratio (SIR) measured the risk for contralateral breast compared to first breast cancer. Results The risks for contralateral breast cancer ranged between 1.85 and 3.79, and they tended to be higher when in situ cancer was diagnosed. Family history and early diagnosis of first cancer increased the risks for contralateral breast cancer, approximately equally for invasive and in situ cancers. The risk for contralateral in situ cancer was 9.01 following two independent invasive cancers. The risk for the same, concordant histology between the first and the contralateral cancer was higher than that for discordant histologies. The risks for concordant histologies were particularly high for mucinous (12.16), comedo (11.74) and lobular (5.06) tumors. When the first lobular cancer was diagnosed before age 45 years, the risk for contralateral lobular cancer was 32.20. Conclusion In situ breast cancer poses an approximately equally high risk as invasive cancer. Family history and earlier age of onset are associated with high risks needing clinical attention.     

Familial clustering of ovarian and endometrial cancers

Data on the association of ovarian cancer with other cancers in families are limited, and no data are available on the involvement of specific morphological types. The nationwide Swedish Family-Cancer Database on 10.2 million individuals and 19175 invasive ovarian cancers was used to calculate standardised incidence ratios (SIRs) and 95% confidence intervals (CIs) for familial ovarian cancer in 0-66-year-old daughters when mothers or sisters were affected. The SIR for concordant ovarian cancers was increased. When the mother or sister had breast cancer, the SIRs were 1.21 and 1.48, respectively; when they had endometrial cancer, the SIRs were 1.45 and 2.53. Multiple myeloma in the mother was associated with a risk of ovarian cancer in the daughter. The risk of endometrioid ovarian cancer was 3.40 in the daughter when the mother presented with endometrial cancer. Our data show a strong familial coupling of ovarian and endometrial cancers, which appears to be specific to the endometrioid morphology.     

Risk of second primary cancers in women diagnosed with endometrial cancer in German and Swedish cancer registries

Along with the increasing incidence and favorable prognosis, more women diagnosed with endometrial cancer may develop second primary cancers (SPCs). We aimed at investigating risk of SPCs after endometrial cancer in Germany and Sweden to provide insight into prevention strategies for SPCs. Endometrial cancer patients diagnosed at age ≥15 years in Germany during 1997–2011 and in Sweden nationwide during 1997–2012 were selected. Standardized incidence ratios (SIRs), calculated as the ratio of observed to expected numbers of cases, were used to assess the risk of a specific second cancer after endometrial cancer for both German and Swedish datasets. Among 46,929 endometrial cancer survivors in Germany and 18,646 in Sweden, overall 2,897 and 1,706 SPCs were recorded, respectively. Significantly elevated SIRs were observed in Germany for ovarian (SIR = 1.3; 95%CI:1.1–1.5) and kidney cancers [1.6 (1.3–1.8)], while in Sweden the SIRs were 5.4 (4.6–6.3) and1.4 (1.0–1.9), respectively. Elevated risk for second ovarian endometrioid carcinoma was pronounced after early (<55 years) onset endometrial cancer in Germany [9.0 (4.8–15)] and Sweden [7.7 (5.1–11)]. In Germany elevated risks were found for second ovarian endometrioid carcinoma after endometrioid histology of first endometrial cancer [6.3 (4.0–9.4)] and for second kidney cancer after clear cell histology of endometrial cancer [4.9 (1.6–11)]. We found exceptionally elevated risk of second ovarian endometrioid carcinoma after endometrial cancer of the same histology or of early onset. Risk for second kidney cancer was also increased, particularly after endometrial cancer of clear cell histology. Cancer prevention strategies should focus on these cancers after endometrial cancer diagnosis.     

Familial effects of prostate and other cancers on lifetime breast cancer risk

Summary Lifetime probabilities of developing breast cancer were calculated for first-degree female relatives of three groups of breast cancer patients: 114 with bilateral cancer, 186 unselected, and 88 males. The patients were classified according to whether they had a family history of prostate, endometrial, or ovarian cancer, or no family history of these cancers. In families of unselected female and male patients with no family history of prostate, endometrial, or ovarian cancer, the lifetime probability of developing breast cancer was 11.4%. The risk increased slightly to 13.5% when these other cancers may or may not have present (i.e., they were ignored, which is the usual method in computing risks) and increased further to 25.5% when prostate, endometrial, or ovarian cancer was present in the family. In families of patients with bilateral cancer the respective risks were 10.9%, 17.3%, and 34.4%. A family history of prostate cancer increased lifetime risk consistently in each of the groups, to 29.0% in the unselected and male groups and to 38.2% in the bilateral group. Endometrial cancer increased risk only in the bilateral group (to 41.8%) as did ovarian cancer (to 54.6%). Increased risk of breast cancer with a family history of endometrial or ovarian cancer appeared to be influenced by families with hereditary breast-ovarian cancer or the cancer family syndrome. The results indicate that prostate cancer, and endometrial and ovarian cancers in some families, can significantly increase breast cancer risk and should be taken into account when counseling women about their breast cancer risk.     

Clinical characteristics of different histologic types of breast cancer

Breast cancer is a heterogeneous disease, though little is known about some of its rarer forms, including certain histologic types. Using Surveillance, Epidemiology, and End Results Program data on 135 157 invasive breast cancer cases diagnosed from 1992 to 2001, relationships between nine histologic types of breast cancer and various tumour characteristics were assessed. Among women aged 50-89 years at diagnosis, lobular and ductal/lobular carcinoma cases were more likely to be diagnosed with stage III/IV, > or =5.0 cm, and node-positive tumours compared to ductal carcinoma cases. Mucinous, comedo, tubular, and medullary carcinomas were less likely to present at an advanced stage. Lobular, ductal/lobular, mucinous, tubular, and papillary carcinomas were less likely, and comedo, medullary, and inflammatory carcinomas were more likely to be oestrogen receptor (ER) negative/progesterone receptor (PR) negative and high grade (notably, 68.2% of medullary carcinomas were ER-/PR- vs 19.3% of ductal carcinomas). In general, similar differences were observed among women diagnosed at age 30-49 years. Inflammatory carcinomas are associated with more aggressive tumour phenotypes, and mucinous, tubular, and papillary tumours are associated with less aggressive phenotypes. The histologic types of breast cancer studied here differ greatly in their clinical presentations, and the differences in their hormone receptor profiles and grades point to their likely different aetiologies.     

Modification of risk for subsequent cancer after female breast cancer by a family history of breast cancer

An increased risk of second primary cancers may depend on many reasons, including therapy for the first cancer and heritable causation. Population level data are not available exploring the risks of subsequent cancers after breast cancer considering a familial history of breast cancers. We used the nation-wide Swedish Family-Cancer Database to investigate such risks, based on 43,398 first invasive female breast cancers. Standardized incidence ratios (SIRs) were calculated for the second cancer after breast cancer using rates for first cancer as a reference. Many cancers at discordant sites were increased after breast cancer. SIRs for subsequent neoplasms in women who had a family history of breast cancer were increased for ovarian (2.0) and endometrial (1.8) cancers and for acute lymphoid leukemia (12.7) and myelofibrosis (9.4). The data suggest that the familial aggregation of breast and endometrial cancers may be explained by yet unidentified heritable causes. The remarkably high risks for second acute lymphoid leukemia and myelofibrosis, both characterized by chromosomal aberrations, in women with a family history of breast cancer may signal heritable defects in the ability to process DNA damage caused by ionizing radiation and chemotherapy.     

Pathology of breast cancer in women with constitutional CHEK2 mutations

The power of association studies between polymorphic genetic variants and breast cancer may be enhanced if the cancer subjects are subclassified by histologic subgroup. In this study we classified 482 unselected breast cancers from Szczecin, Poland by histology (ductal, lobular, medullary, other). All women were genotyped for three founder mutations in the CHEK2 gene (1100delC, IVS2 + 1G > A and I157T). There was no significant overall association between CHEK2 and breast cancer (OR = 1.3; p = 0.30), but among those with lobular carcinoma the association with the I157T missense mutation was very strong (OR = 6.6; p > 0.0001). This is the first report to demonstrate that different mutations of the same gene may be associated with specific histologic subtypes of cancer.     

Familial breast carcinoma risks by morphology: a nationwide epidemiologic study from Sweden

BACKGROUND: Familial risks in patients with breast carcinoma have not been assessed by morphologic types of medically verified cancers. Reliable data on familial risks would help to establish prevention programs and guide clinical decisions. METHODS: We used the nationwide Swedish Family-Cancer Database to calculate standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for invasive and in situ breast carcinomas in women with mothers and sisters. This database has information on 10.2 million individuals and on more than 13,000 morphology-specific breast carcinomas. RESULTS: SIRs for all invasive breast carcinomas were 1.82 (95% CI 1.71-1.93) for breast carcinoma in the mother and 1.89 (1.70-2.01) for breast carcinoma in a sister. The respective risks were 1.81 and 1.85 for a mother and sisters with ductal breast carcinoma. The SIRs were equally for lobular, tubuloductal, comedo, and mucinous breast carcinomas. However, the SIRs for lobular carcinoma were lower than those for the ductal type, whereas the opposite trend was noted for the comedo and mucinous type; none of the differences were significant. The risks for all morphologic types were highest when both a mother and a sister were affected, SIR 3.19 (2.36-4.22). The risks for in situ breast carcinomas were 2.09 (1.78-2.44) for an affected mother, 2.24 (1.88-2.85) for an affected sister, and 5.23 (2.59-9.39) when both a mother and a sister were affected. CONCLUSIONS: The data suggest that the familial risk of breast carcinoma is independent of the morphologic type. The higher risks in in situ cancer may be due to medical surveillance. The risks were identical from a mother or sister proband, suggesting that recessive effects are unlikely as a heritable cause of breast carcinoma.     

Familial and second primary pancreatic cancers: a nationwide epidemiologic study from Sweden

Familial risk of pancreatic cancer has been mainly assessed through case-control studies based on reported but not medically verified cancers in family members. We used the nationwide Swedish Family-Cancer Database on 10.2 million individuals and 21,000 pancreatic cancers to calculate standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for pancreatic cancer in 0- to 66-year-old offspring of parents with pancreatic or other specified tumors. Additionally, SIRs for second primary pancreatic cancers were analyzed after any first neoplasm. SIRs for pancreatic cancer (1.68, 95% CI 1.16-2.35) and pancreatic adenocarcinoma (1.73, 95% CI 1.13-2.54) were increased when a parent presented with pancreatic cancer. The risk was not dependent on diagnostic age of offspring or parents. Pancreatic cancer was associated with parental lung, rectal or endometrial cancer and with melanoma. SIRs for pancreatic cancer were 10.01 and 7.96 among offspring who were diagnosed before age 50 years when parents were diagnosed with squamous cell and adenocarcinoma of the lung, respectively, before age 60 years. The population-attributable proportion of familial pancreatic cancer was 1.1%. Risks for second pancreatic cancers were increased in men and women after small intestinal, colon and bladder cancer. The degree of familial clustering for pancreatic cancer and its population-attributable proportion were lower than the data cited in the literature. Clustering of pancreatic cancer with sites presenting in hereditary nonpolyposis colorectal cancer was noted. The strong association of pancreatic and lung cancers is puzzling, and it remains unclear to what extent this represents familial sharing of smoking habits.     

Familial association of colorectal adenocarcinoma with cancers at other sites

Data on the familial associations of colorectal cancer (CRC) of adenocarcinoma histology are limited, but they are of interest because they may give us clues about as yet unknown family clusters. We calculated standardised incidence ratios (SIRs) for right- and left-sided colon cancer and rectal cancer in offspring using data from the Swedish Family-Cancer Database covering familial tumours from 1991 to 2000. The offspring were at an increased risk of developing colon adenocarcinoma when parents presented with CRC (SIR 1.81), endometrial (SIR 1.52) and kidney (SIR 1.42) cancers. The SIRs in siblings were increased when a co-sibling was diagnosed with CRC (SIR 3.26), myeloma (SIR 2.65) and leukaemia (SIR 2.53). Right-sided colon cancer was associated with familial pancreatic, squamous cell skin cancers, thyroid gland cancer and Hodgkin's disease. Left-sided colon cancer was associated with testicular cancers. Rectal cancer was associated with cervical and genital cancers in mothers. Most of the findings were consistent with data on known cancer syndromes. A new association was noted where rectal cancer in offspring was related to cervical and female genital cancers in mothers through an unknown mechanism. Hodgkin's disease and myeloma were also associated with right-sided colon cancer in offspring. The association with carcinoma of the testis, renal parenchyma, skin and leukaemia need to be confirmed in an independent series.     

Familial risk of endometrial cancer after exclusion of families that fulfilled Amsterdam, Japanese or Bethesda criteria for HNPCC.

BACKGROUND: Endometrial cancer is the second most common lesion within hereditary non-polyposis colorectal cancer (HNPCC) syndrome. The importance of the non-HNPCC genetic predisposition to endometrial cancer is unclear, and the familial aggregation of endometrial cancer after exclusion of HNPCC families may offer valuable clues about the involvement of non-HNPCC-related genes. PATIENTS AND METHODS: The families of the nationwide Swedish Family-Cancer Database were classified as HNPCC families according to the Amsterdam I or II, the modified Amsterdam, the Japanese and the Bethesda criteria. Standardized incidence ratios (SIRs) for endometrial cancer when parents or siblings were diagnosed with cancer at the most common sites were calculated before and after exclusion of HNPCC families. RESULTS: The proportion of individuals in the families with endometrial cancer was highest when the criteria required three cancers within a family or multiple HNPCC-related cancers in the same individual. Consideration of the Amsterdam or the Japanese criteria hardly reduced the familial aggregation of endometrial cancer. After exclusion of families that fulfilled the Bethesda criteria, SIRs were significant when the parents were diagnosed with endometrial or thyroid gland cancers; 75.7% (95% confidence interval 60% to 99.1%) of the familial cases of endometrial cancer were not related to HNPCC according to the Bethesda criteria. The reduction of SIRs for cancers at the colon, pancreas, prostate and ovary was limited when the Bethesda criteria were applied. However, the Bethesda criteria identified most of the familial aggregation when endometrial cancers were diagnosed before the age of 55 years. CONCLUSIONS: The data suggest that additional effects, not related to HNPCC, contribute to the familial aggregation of endometrial cancer.     

Endometrial cancer in the family-cancer database.

Endometrial cancer was studied in the Swedish Family-Cancer Database, updated in 1999 to cover individuals born after 1934 with their biological parents, totaling 9.6 million persons. Cancer data were obtained from the Swedish Cancer Registry from 1958 to 1996 and included over 20,000 cases of endometrial cancer. Seventy-six families were identified in which both the mother and the daughter had endometrial cancer, giving a familial standardized incidence ratio (SIR) of 3.19 for daughters and 2.78 for mothers. The risk depended inversely on the age at diagnosis, and the risk was almost 10 in daughters who were diagnosed before age 50 when their mothers were also diagnosed before that age. The discordant cancer site that associated with endometrial cancer between the two generations was colon, with a SIR of 1.44-1.68. However, when the maternal endometrial cancer was diagnosed before age 50, increased SIRs were observed in daughters or sons for rectal, pancreatic, nervous system, breast, and ovarian cancers. Second cancers were followed in females diagnosed with endometrial cancer, and the highest overall risks were observed for ovarian and connective tissue cancers; colorectal cancers were also clearly in excess. Among the other family members of the 76 families in which both mother and daughter were affected with endometrial cancer, there were 11 cases of colorectal cancer. When a sister was affected in such families, the SIR of endometrial cancer was 31.40, and the median diagnostic age was several years lower than in endometrial cancer families in which no colorectal cancers were found. Many of these families may have hereditary nonpolyposis colorectal carcinoma syndrome. However, the risk of endometrial cancer was increased even in families presenting no colorectal cancers.     

Increased cancer risks for relatives of very early-onset breast cancer cases with and without BRCA1 and BRCA2 mutations

Background:

Little is known regarding cancer risks for relatives of women with very early-onset breast cancer.

Methods:

We studied 2208 parents and siblings of 504 unselected population-based Caucasian women with breast cancer diagnosed before age 35 years (103 from USA, 124 from Canada and 277 from Australia), 41 known to carry a mutation (24 in BRCA1, 16 in BRCA2 and one in both genes). Cancer-specific standardised incidence ratios (SIRs) were estimated by comparing the number of affected relatives (50% verified overall) with that expected based on incidences specific for country, sex, age and year of birth.

Results:

For relatives of carriers, the female breast cancer SIRs were 13.13 (95% CI 6.57–26.26) and 12.52 (5.21–30.07) for BRCA1 and BRCA2, respectively. The ovarian cancer SIR was 12.38 (3.1–49.51) for BRCA1 and the prostate cancer SIR was 18.55 (4.64–74.17) for BRCA2. For relatives of non-carriers, the SIRs for female breast, prostate, lung, brain and urinary cancers were 4.03 (2.91–5.93), 5.25 (2.50–11.01), 7.73 (4.74–12.62), 5.19 (2.33–11.54) and 4.35 (1.81–10.46), respectively. For non-carriers, the SIRs remained elevated and were statistically significant for breast and prostate cancer when based on verified cancers.

Conclusion:

First-degree relatives of women with very early-onset breast cancer are at increased risk of cancers not explained by BRCA1 and BRCA2 mutations.     

Pregnancy experience in women who later developed oestrogen- related cancers (Denmark)

Objectives: There has been speculation that women with oestrogen-related cancers have been exposed to high levels of oestrogen in earlier life and therefore also during their pregnancies prior to the disease. For this reason we examined signs of reproductive outcome related to oestrogen exposure such as twinning, sex ratio, birth weight and congenital malformation in women who later were diagnosed with breast cancer, endometrial or ovarian cancer.Methods: For 5213 children born to women who later developed breast cancer, 557 children born to women who later developed ovarian cancer and 173 children born to mothers with endometrial cancers we selected as a control four times as many newborns of mothers without these cancers after matching for mothers'; parity, age, date of birth and hospital attended. All data were extracted from existing nationwide files. Most of the women's reproductive lives fell within the period of the birth registry from 1973 to 1993.Results: No differences in sex ratio, birth weight or malformation were found between the newborns to cancer or control mothers in any of the cancer groups studied. The only significant findings were less than expected births of twins to mothers who later developed cancer of the ovaries and a higher proportion of newborns with a birth weight over 4000g in the cancer corpus uterus group.Conclusion: Although the amount of information is limited for endometrial and ovarian cancers, we found no strong indication of elevated oestrogen levels during pregnancy.     

The association between oral contraceptive use and lobular and ductal breast cancer in young women

Recent reports indicate that the incidence of lobular breast cancer is increasing at a faster rate than ductal breast cancer, which may be due to the differential effects of exogenous hormones by histology. To address this issue, we examined whether the relationship between oral contraceptive use and incident breast cancer differs between lobular and ductal subtypes in young women. A population-based sample of in situ and invasive breast cancer cases between ages 20 and 44 were recruited from Atlanta, GA; Seattle-Puget Sound, WA and central New Jersey. Controls were sampled from the same areas by random-digit dialing, and were frequency matched to the expected case age distribution. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using polytomous logistic regression. Among the 100 lobular cancers, 1,164 ductal cancers, and 1,501 controls, the odds ratios for oral contraceptive ever use were 1.10 (95% CI = 0.68-1.78) for lobular cancers and 1.21 (95% CI = 1.01-1.45) for ductal cancers, adjusted for study site, age at diagnosis, and pap screening history. Our results suggest that the magnitude of the association between ever use of oral contraceptives and breast cancer in young women does not vary strongly by histologic subtype. These results are similar to previous studies that report little difference in the effect of oral contraceptive use on breast cancer by histology.     

Post screen-detected breast cancer within the Screening Mammography Program of British Columbia

The histological characteristics and extent of mammographic density were compared between 170 post screen-detected (PSD) breast cancers and 466 screen-detected (SD) breast cancers in women attending the Screening Mammography Program of British Columbia. In addition, methods of detection and clinical presentation for the PSD cancers were examined. Invasive ductal, comedo, and medullary carcinoma were significantly more common in PSD cancer in women under age 50 years, and invasive ductal carcinoma in women over age 50 years. Mammographic density was more common in PSD cancers for all age groups under 70 years. The majority of PSD cancers were node negative with no evidence of metastases; however, they tended to be of more advanced stage than SD cancer. Most PSD cancers regardless of age were initially found by the woman herself, presenting as a palpable mass, and the likelihood of being detected within 12 months of the last screening mammogram was higher at younger ages.     

Familial risk for histology-specific bone cancers: an updated study in Sweden

We used the nation-wide Swedish Family-Cancer Database to examine the familial risks of histology-specific bone cancers in offspring by parental or sibling probands. Adjusted standardised incidence ratios (SIRs) were used to measure the risk. Among the 1327 offspring bone cancers, only two parent-offspring pairs and one sibling pair were noted with concordant bone cancer but the SIRs were not significant. Significant associations were observed in specific histological types or specific age groups, some of which may be chance findings arising from multiple comparisons. However, the risk of early-onset (< 25 years) osteosarcoma in offspring was significantly increased when mothers presented with breast cancer (1.7) and melanoma (2.9), suggesting that Li-Fraumeni syndrome could partly explain this familial aggregation. Other associations, such as childhood osteosarcoma with parental liver cancer, Ewing's sarcoma with kidney cancer and giant cell sarcoma with maternal breast cancer, were novel findings and may be related to other familial diseases.     

Association of brain tumours with other neoplasms in families

We used the nationwide Swedish Family-Cancer Database to analyse the association of histology-specific brain tumours with other cancers in family members. Among 0-68-year-old offspring, 9414 patients with brain tumours were identified from 1961 to 2000, of whom, 3387 parents were diagnosed with any primary neoplasm. Astrocytoma, meningioma and neurinoma were the main histological types. Increased standardised incidence ratios (SIRs) were found for brain tumours in association with cancers at sites that are known features in recognised syndromes, such as haemangioblastoma and renal cancer in von Hippel-Lindau disease. In addition, an association between astrocytoma and melanoma was recognised. Among as yet unknown clustering, neurinoma was associated with testicular cancer and myeloma; meningioma was associated with cervical cancer; astrocytoma was associated with prostate cancer; ependymoma was associated with breast cancer. Although some of these may feature a true tumour cluster, they need to be confirmed in another setting.     

Relationship between established breast cancer risk factors and risk of seven different histologic types of invasive breast cancer.

BACKGROUND: Important differences in the contributions of certain exposures to the risks of ductal versus lobular breast carcinomas have been observed, but few studies have evaluated the relationships between established breast cancer risk factors and other histologic types. METHODS: Information on family history of cancer and reproductive, hormonal, anthropometric, and lifestyle characteristics were collected in a multicenter population-based case-control study consisting of 3,463 ductal, 274 lobular, 261 ductal-lobular, 91 medullary, 77 tubular, 70 comedo, and 61 mucinous invasive breast carcinoma cases (ages 35-64 years, newly diagnosed 1994-1998) and 4,682 controls. Associations between each of these histologic types and various exposures were evaluated using polytomous regression. RESULTS: Heterogeneity in the risks of different histologic types of breast cancer was observed for three exposures: menopausal hormone use, body mass index (BMI), and alcohol consumption. Specifically, current use of unopposed estrogen was associated with a reduced risk of ductal carcinoma and increased risk of comedocarcinoma, and current use of estrogen and progestin was associated with elevated risks of ductal-lobular and tubular carcinomas. Among postmenopausal women, BMI was only inversely related to risk of ductal-lobular carcinoma, and alcohol use was only positively related to risk of lobular carcinoma. CONCLUSIONS: Variations in the associations between known breast cancer risk factors and risk of different breast cancer histologies were observed. Although these findings require confirmation, and the analyses of some histologic groups were limited by small sample sizes, they provide some insight into the different etiologies of various histologic subtypes of breast cancer.     

Cancer risks in first-generation immigrants to Sweden

We used the nationwide Swedish Family-Cancer Database to analyse cancer risks in 613,000 adult immigrants to Sweden. All the immigrants had become parents in Sweden and their median age at immigration was 24 years for men and 22 years for women. We calculated standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for 18 cancer sites using native Swedes as a reference. Data were also available from compatriot marriages. All cancer was decreased by 5% and 8% for immigrant men and women, respectively. However, most of the male increase was due to lung cancer for which male immigrants showed a 41% excess. Among individual cancer sites and immigrant countries, 110 comparisons were significant, 62 showing protection and 48 an increased risk. Most of the differences between the rates in immigrants and Swedes could be ascribed to the variation of cancer incidence in the indigenous populations. Some high immigrant SIRs were 5.05 (n = 6, 95% CI 1.82-11.06) for stomach cancer in Rumanian women and 2.41 (41, 1.73-3.27) for lung cancer in Dutch men. At some sites, such as testis, prostate, skin (melanoma), kidney, cervix and nervous system, the SIRs for immigrants were decreased; in some groups of immigrants SIRs were about 0.20. The highest rates for testicular cancer were noted for Danes and Chileans. Women from Yugoslavia and Turkey had an excess of thyroid tumours. All immigrant groups showed breast, endometrial and ovarian cancers at or below the Swedish level but the differences were no more than 2-fold.