Familial and second esophageal cancers: a nation-wide epidemiologic study from Sweden

A few case-control studies have been published on familial risks in esophageal cancer. Reliable data on familial risks are needed for prevention and clinical decisions. We used the nation-wide Swedish Family-Cancer Database on 10.1 million individuals and close to 6000 esophageal cancers to calculate standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for esophageal cancer in 0-66-year-old offspring by cancers in family members. Additionally, SIRs for second esophageal cancers were analyzed. The SIR for esophageal cancer was 3.91 (95% CI 1.55-7.35) when a parent presented with esophageal cancer and 4.91 (95% CI 1.77-9.62) when a parent presented with squamous cell carcinoma. The sibling risk for esophageal cancer was increased but was based on 1 pair only. The population-attributable proportion of familial esophageal cancer was 0.70%. Risks for second esophageal cancers were increased after upper aerodigestive tract, esophageal, stomach, larynx, and lung cancers. The data on second cancers suggest that environmental factors are important for esophageal cancer and probably contribute to the familial clustering. However, the high familial risk of 3.91 is unlikely without the involvement of heritable factors. The population-attributable proportion of familial esophageal cancer is small.     

Familial and second lung cancers: a nation-wide epidemiologic study from Sweden

The role of hereditary factors in tumor development has been less well understood for lung cancer than for many other human neoplastic diseases. The nation-wide Swedish Family-Cancer Database was used on 10.2 million individuals and 4524 lung cancers to calculate standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for histological subtypes of lung cancer in 0-66-year-old offspring by cancers in family members. Additionally, SIRs for second lung cancers were analyzed. SIRs in offspring for all lung cancer were increased to 1.87 (95% CI 1.66-2.10), adenocarcinoma to 2.15 (1.77-2.59) and squamous cell carcinoma to 1.86 (1.39-2.44) when a parent presented with lung cancer. The familial risk was not dependent on diagnostic age. Lung cancer associated with parental rectal, cervical, kidney, urinary bladder and endocrine gland cancer. The population attributable fraction of familial lung cancer was 2.97%. Risks for second lung cancers were increased in men and women after smoking and life style related sites, and after skin cancer, non-Hodgkin's lymphoma and Hodgkin's disease.     

Familial carcinoid tumors and subsequent cancers: a nation-wide epidemiologic study from Sweden.

Carcinoids are rare neuroendocrine tumors, mainly located in the bowel, stomach and lung. Familial risks in carcinoid tumours are not well known apart from multiple endocrine neoplasia 1 (MEN1). We used the nation-wide Swedish Family-Cancer Database on 10.1 million individuals for assessment. Carcinoid tumors were retrieved from the Cancer Registry covering the years 1958-1998. The offspring generation, aged 0-66 years, accumulated 190 million person-years at risk. The age-adjusted incidence rates were 0.76 for men and 1.29/100,000 for women. Standardized incidence ratios (SIRs) were calculated for offspring when their parents had a carcinoid or any other cancer. When parents presented with carcinoids, SIRs for offspring were 4.35 (n = 8, 95% CI 1.86-7.89) for small intestinal and 4.65 (n = 4, 95% CI 1.21-10.32) for colon carcinoids. If both offspring and parents presented with small intestinal carcinoids, the SIR was 12.31 (n = 4, 95% CI 3.20-27.34). Offspring carcinoids were also increased if parents presented with bladder and endocrine gland tumors, the latter association probably partially due to MEN1. Risks for second cancers were increased, particularly at sites where familial risks were found, including carcinoids in the small intestine.     

Familial colorectal adenocarcinoma and hereditary nonpolyposis colorectal cancer: a nationwide epidemiological study from Sweden

Although estimates are available of the proportion of hereditary nonpolyposis colorectal cancer (HNPCC) among all colorectal cancer (CRC), its proportion among familial CRC is unclear. We estimated these proportions epidemiologically from the nationwide Swedish Family-Cancer Database on 9.6 million individuals. Colorectal adenocarcinomas were retrieved from the Cancer Registry covering years 1958-1996. Standardized incidence ratios (SIRs) were calculated for offspring (aged less than 62 years) when their parent had colorectal adenocarcinoma. In 9.82% of all families, an offspring and a parent were affected, giving a population attributable proportion of 4.91% and a familial SIR of 2.00. When offspring and parents shared the anatomic site, the SIR was 2.32 for proximal and 2.00 for distal CRC. When offspring were diagnosed before age 40 years and parents before age 50 years, the SIR was 25.72 for familial proximal CRC. In older age groups familial risks did not differ between proximal and distal CRC. Familial risks were increased also for endometrial, small intestinal and gastric cancers, manifestations in HNPCC. Depending on which assumptions were made, HNPCC was calculated to account for 20 to 50% of familial CRC, corresponding to 1 or 2.5% of all CRC among 0-61-year-old individuals.     

Familial colorectal adenocarcinoma from the Swedish Family-Cancer Database.

Familial risks for colorectal (CRC) adenocarcinoma were characterized from the Swedish Family-Cancer Database covering 9.6 million individuals, whose family relationships and cancers were obtained from registered sources, not sensitive to reporting or ascertainment bias. Cancer cases were retrieved from the Swedish Cancer Registry from years 1958-96. Standardized incidence ratios (SIRs) were calculated based on gender-, age-, period- and tumor type specific rates. A total of 4,794 and 67,925 CRCs were recorded in offspring and parents, respectively. For colon and rectal adenocarcinoma, the SIRs in offspring were 2.28 and 1.68 by parental CRC adenocarcinoma, giving attributable proportions of 6.45 and 3.31%, respectively. The SIR of CRC was over 10 when both offspring and parents were diagnosed at a young age. The risk for parental CRC adenocarcinoma was over 100 when 2 or more children were affected. The risk in siblings was also very high when a parent was affected. The familial cancer sites that associated with CRC were those typical of hereditary nonpolyposis colorectal cancer (HNPCC). This is the largest study published on familial CRC and the only one reporting specifically on adenocarcinoma. The data suggest that HNPCC is the largest single disease entity among CRCs, probably accounting for less than 50% of familial CRC. Other familial components appear heterogeneous, characterized by incomplete penetrance, recessive mode of inheritance and few associated tumor sites.     

Familial risk of cancer: data for clinical counseling and cancer genetics

Familial risks for cancer are important for clinical counseling and understanding cancer etiology. Medically verified data on familial risks have not been available for all types of cancer. The nationwide Swedish Family-Cancer Database includes all Swedes born in 1932 and later (0-to 68-year-old offspring) with their parents, totaling over 10.2 million individuals. Cancer cases were retrieved from the Swedish Cancer Registry up to year 2000. Standardized incidence ratios (SIR) and 95% confidence limits (CI) were calculated for age-specific familial risk in offspring by an exact proband status. The familial risks for offspring cancer were increased at 24/25 sites from concordant cancer in only the parent, at 20/21 sites from a sibling proband and at 12/12 sites from a parent and sibling proband. The highest SIRs by parent were for Hodgkin's disease (4.88) and testicular (4.26), non-medullary thyroid (3.26), ovarian (3.15) and esophageal (3.14) cancer and for multiple myeloma (3.33). When a sibling was affected, even prostate, renal, squamous cell skin, endocrine, gastric and lung cancer and leukemia showed SIRs in excess of 3.00. The highest cumulative risks were found for familial breast (5.5%) and prostate (4.2%) cancers. We identified reliable familial risks for 24 common neoplasms, most of which lack guidelines for clinical counseling or action level. If, for example, a familial SIR of 2.2 would be use as an action level, counseling would be needed for most cancers at some diagnostic age groups. The present data provide the basis for clinical counseling.     

The Swedish Family-Cancer Database: Update,Application to Colorectal Cancer and Clinical Relevance

The Swedish Family-Cancer Database has been used for almost 10 years in the study of familial risks at all common sites. In the present paper we describe some main features of version VI of this Database, assembled in 2004. This update included all Swedes born in 1932 and later (offspring) with their biological parents, a total of 10.5 million individuals. Cancer cases were retrieved from the Swedish Cancer Registry from 1958-2002, including over 1.2 million first and multiple primary cancers and in situ tumours. Compared to previous versions, only 6.0% of deceased offspring with a cancer diagnosis lack any parental information. We show one application of the Database in the study of familial risks in colorectal adenocarcinoma, with defined age-group and anatomic site specific analyses. Familial standardized incidence ratios (SIRs) were determined for offspring when parents or sibling were diagnosed with colon or rectal cancer. As a novel finding it was shown that risks for siblings were higher than those for offspring of affected parents. The excess risk was limited to colon cancer and particularly to right-sided colon cancer. The SIRs for colon cancer in age matched populations were 2.58 when parents were probands and 3.81 when siblings were probands; for right-sided colon cancer the SIRs were 3.66 and 7.53, respectively. Thus the familial excess (SIR-1.00) was more than two fold higher for right-sided colon cancer. Colon and rectal cancers appeared to be distinguished between high-penetrant and recessive conditions that only affect the colon, whereas low-penetrant familial effects are shared by the two sites. Epidemiological studies can be used to generate clinical estimates for familial risk, conditioned on numbers of affected family members and their ages of onset. Useful risk estimates have been developed for familial breast and prostate cancers. Reliable risk estimates for other cancers should also be seriously considered for routine clinical recommendations, because practically all cancers show a familial effect and the risks are high for some of the rare neoplasms. The implementation of a unified management plan for familial cancers at large will be a major challenge to the clinical genetic counselling community.     

Familial invasive and borderline ovarian tumors by proband status,age and histology

Age-specific familial risks in ovarian cancer have not been assessed by histologic types of medically verified cancers. We used the nationwide Swedish Family-Cancer Database on 10.2 million individuals and 19,175 invasive and 3,436 borderline ovarian cancers to calculate, by affected family members, standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for familial ovarian cancer in 0-66 year old daughters. SIRs for all invasive ovarian cancer were 2.68 (95% CI 2.22-3.21) by ovarian cancer in mother, 2.94 (1.40-5.94) by an affected sister and 24.03 (6.12-74.46) by both an affected mother and sister. The population-attributable fraction from mothers was 2.52%. Seropapillary cystadenocarcinoma showed the highest familial risk, but the effect of histopathol subtype could not be fully assessed because of lack of data in probands. Age-specific data showed some early-onset components and an unusual maximal incidence in the 40s. A comparison to an earlier study on BRCA1/2 mutation analysis and relative risks of ovarian and breast cancer suggests that these mutations could account for 26% of the familial aggregation of ovarian cancer. Histopathology and age of onset appear to be important attributes of familial ovarian cancer, suggesting that further gene identification efforts should target a specific histopathology in early-onset patients.     

Familial risks for colorectal cancer show evidence on recessive inheritance

Recent molecular genetic data have become available on a recessive inheritance in colorectal cancer (CRC). We wanted to search for evidence for recessive inheritance from a population-based family data set, which is not sensitive to reporting or ascertainment bias. The nationwide Swedish Family-Cancer Database covered 10.3 million individuals whose invasive CRCs of adenocarcinoma histology were followed from 1991 to 2000. Age of the offspring and parental populations was limited to less than 69 years. Standardized incidence ratios (SIRs) were calculated for site-specific CRC in offspring whose parents or siblings were diagnosed with CRC. A total of 6,774 offspring were recorded with CRC, whose risk was 2.13 when a parent was diagnosed with CRC and it was 2.75 when a sibling was affected. The SIRs for right-sided colon cancer were 7.53 among siblings and 3.66 among offspring of affected parents, giving a 1.8-fold excess familial risk among siblings. Colon cancer among the 0- to 68-year-old population accounted for about 25% of all colon cancers. Examination of all cancers in family members of the affected siblings did not reveal large contribution by known syndromes, such as hereditary nonpolyposis colorectal cancer. The most likely explanation to the high risk of right-sided colon cancer among siblings is a recessive inheritance, which would account for 0.75% of all CRCs. Its high prevalence and predilection to right-sided colon suggest that only a small proportion of this familial aggregation could be due to MYH mutations.     

Inherited predisposition to early onset lung cancer according to histological type

The role of hereditary factors in lung cancer is less well understood than in many other human neoplastic diseases. We used a nation-wide family dataset to search for evidence for a genetic predisposition in lung cancer. The Swedish Family-Cancer Database includes all Swedes born in 1932 and later (0- to 68-year-old offspring) with their parents, totaling over 10.2 million individuals. Cancer cases were retrieved from the Swedish Cancer Registry up to year 2000. Standardized incidence ratios (SIR) and 95% confidence limits (CI) were calculated for age-specific familial risks in offspring by parental or sibling proband, separately. A Kappa test was used to examine the association between familial risk and histology. Compared to the rate of lung cancers among persons without family history, a high risk by parental family history in adenocarcinoma (2.03) and large cell carcinoma (2.14) was found, and only a slightly lower risk was found among patients with squamous cell carcinoma (1.63) and small cell carcinoma (1.55). Among siblings, an increased risk was shown for concordant adenocarcinoma and small cell carcinoma at all ages and for all histological types when cancer was diagnosed before age 50. At young age, risks between siblings were higher than those between offspring and parents. The present data suggest that a large proportion of lung cancers before age 50 years appears to be heritable and probably due to a high-penetrant recessive gene or genes that predispose to tobacco carcinogens; however, this hypothesis needs to be tested in segregation analysis with a large number of pedigrees.     

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.     

The Swedish Family-Cancer Database: Update,Application to Colorectal Cancer and Clinical Relevance

The Swedish Family-Cancer Database has been used for almost 10 years in the study of familial risks at all common sites. In the present paper we describe some main features of version VI of this Database, assembled in 2004. This update included all Swedes born in 1932 and later (offspring) with their biological parents, a total of 10.5 million individuals. Cancer cases were retrieved from the Swedish Cancer Registry from 1958-2002, including over 1.2 million first and multiple primary cancers and in situ tumours. Compared to previous versions, only 6.0% of deceased offspring with a cancer diagnosis lack any parental information. We show one application of the Database in the study of familial risks in colorectal adenocarcinoma, with defined age-group and anatomic site specific analyses. Familial standardized incidence ratios (SIRs) were determined for offspring when parents or sibling were diagnosed with colon or rectal cancer. As a novel finding it was shown that risks for siblings were higher than those for offspring of affected parents. The excess risk was limited to colon cancer and particularly to right-sided colon cancer. The SIRs for colon cancer in age matched populations were 2.58 when parents were probands and 3.81 when siblings were probands; for right-sided colon cancer the SIRs were 3.66 and 7.53, respectively. Thus the familial excess (SIR-1.00) was more than two fold higher for right-sided colon cancer. Colon and rectal cancers appeared to be distinguished between high-penetrant and recessive conditions that only affect the colon, whereas low-penetrant familial effects are shared by the two sites. Epidemiological studies can be used to generate clinical estimates for familial risk, conditioned on numbers of affected family members and their ages of onset. Useful risk estimates have been developed for familial breast and prostate cancers. Reliable risk estimates for other cancers should also be seriously considered for routine clinical recommendations, because practically all cancers show a familial effect and the risks are high for some of the rare neoplasms. The implementation of a unified management plan for familial cancers at large will be a major challenge to the clinical genetic counselling community.     

Familial multiple primary lung cancers: a population-based analysis from Sweden

Multiple primary cancers arise because of inherited or acquired deficiencies, and their causes may depend on the first primary cancer, or they may be entirely independent. We used a nation-wide family dataset to search for evidence for a genetic predisposition to lung cancer. The Swedish Family-Cancer Database includes all Swedes born in 1932 and later with their parents, totalling over 10.2 million individuals. Cancer cases were retrieved from the Swedish Cancer Registry up to year 2000. Standardized incidence ratios (SIR) and 95% confidence limits (CI) were calculated for first and second primary lung cancers by a family history. The incidence of second primary lung cancer was nine times higher among cases with familial lung cancer compare to that of first primary lung cancer. The proportion of multiple primary lung cancer patients with family history for lung cancer was 4.7% (9/190) for men and 6.5% (5/77) for women. Lung cancer patients with a family history of lung cancer were at a significantly increased risk for subsequent primary lung cancer among both men (SIR=9.89, 95%CI 4.48-18.66) and women (SIR=17.86, 95%CI 5.63-42.00). The corresponding SIRs in patients without a family history were 2.04 (95%CI 1.75-2.36) and 5.10 (95%CI 3.99-6.43) for men and women, respectively. The present study suggests that the development from the first primary lung cancer to the second primary lung cancer may be more strongly affected by genetic factor than the first primary lung cancer.     

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.     

Familial aggregation of early-onset cancers in early-onset breast cancer families

The risk of early-onset (EO) breast cancer is known to be increased in relatives of EO breast cancer patients, but less is known about the familial risk of other EO cancers. We assessed familial risks of EO cancers (aged ≤40 years) other than breast cancer in 54 753 relatives of 5562 women with EO breast cancer (probands) by using a population-based cohort from Finland. Standardized incidence ratios (SIRs) and 95% confidence intervals (CI) were estimated by using gender-, age- and period-specific cancer incidences of the general population as reference. The risk of any cancer excluding breast cancer in first-degree relatives was comparable to population cancer risk (SIR 0.99, 95% CI: 0.84-1.16). Siblings' children of women with EO breast cancer were at an elevated risk of EO testicular and ovarian cancer (SIR = 1.74, 95% CI: 1.07-2.69 and 2.69, 95% CI: 1.08-5.53, respectively). The risk of EO pancreatic cancer was elevated in siblings of the probands (7.61, 95% CI: 1.57-22.23) and an increased risk of any other cancer than breast cancer was observed in children of the probands (1.27, 95% CI: 1.03-1.55). In conclusion, relatives of women with EO breast cancer are at higher familial risk of certain discordant EO cancers, with the risk extending beyond first-degree relatives.     

Familial association of histology specific breast cancers with cancers at other sites

Breast cancer histologies show important differences in their incidence pattern, method of detection and management. Aggregation of breast cancer occurs also in families diagnosed for cancer at sites different from the breast. Therefore, the familial association of histology specific breast cancers with cancers at other sites is of great interest. The nationwide Swedish Family-Cancer Database was used to calculate standardised incidence ratios (SIRs) for breast cancer when parents or sibling were diagnosed with cancer at the most common sites. Significant SIRs were found when parents had breast, ovarian, laryngeal, endometrial, prostate, lung and colon cancers. If women were diagnosed before the age of 50 years, the SIRs were significant when parents were diagnosed with breast, ovarian, and prostate cancers, and leukaemia, and when siblings were diagnosed with squamous cell skin, pancreatic, breast and endometrial cancers. If mothers were diagnosed with breast cancer, histology-specific SIRs were ranked as comedo > tubular > ductal > lobular; SIR for medullary carcinoma was not significant but it was high when mothers presented with ovarian cancer. Other associations were between the upper aerodigestive tract and lobular, colon and comedo, larynx and ductal cancer. Moreover, cervical cancer was associated with comedo and endometrial cancer with the medullary histology. In conclusion, histology-specific breast cancers were associated with specific cancer sites and the strength of the association varied among histologies.     

Multiple primary cancers of the colon, breast and skin (melanoma) as models for polygenic cancers

To assess the role of family history in the development of multiple primary cancer, the Swedish Family-Cancer Database was used to analyze second primary cancer in patients born in 1935 to 1996 with an initial primary cancer of the colon, breast and skin (melanoma) by familial cancer in first-degree relatives. Standardized incidence ratios (SIRs) were calculated from site-, sex- and age-specific rates for all persons (offspring) born in 1935 to 1996. Familial risk (SIR) was calculated for the first and second primary cancers in offspring. A Poisson regression analysis was also performed to assess the risk factors for occurrence of second primary cancer. The familial proportion of multiple primary cancers was 29.0% (9/31) for colon, 16.3% (122/747) for female breast and 14.5% (17/117) for melanoma. Compared with all offspring, patients with family history were at a much higher and significantly increased risk for subsequent primary cancer at colon (SIR = 59.1), skin (SIR = 48.2) and female breast (SIR = 7.9). The corresponding SIRs in patients without family history were 13.8, 10.5 and 5.2 at the three sites. The ratios for incidence of second primary to first primary were highest when diagnosis age was less than 40 years. A Poisson regression analysis showed that family history was one of the major risk factors for occurrence of multiple primary cancers at colon, breast and skin. The high risk of second cancer, even in the absence of family history, would be consistent with a polygenic model of carcinogenesis.     

Familial and second gastric carcinomas: a nationwide epidemiologic study from Sweden

BACKGROUND: Familial risks in gastric carcinoma have been assessed mainly through case-control studies based on reported but not medically verified carcinomas in family members. Reliable data on familial risks are needed for prevention and clinical decisions. METHODS: The authors used the nationwide Swedish Family-Cancer Database on 10.2 million individuals and more than 34,000 gastric carcinomas to calculate standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for gastric carcinoma in offspring, from birth to 66 years old, by carcinomas in family members. In addition, SIRs for second gastric carcinomas were analyzed. RESULTS: Standardized incidence ratios for gastric carcinoma were 1.31 (95% CI, 0.97-1.70) and 1.47 (95% CI, 1.08-1.92) when a parent presented with gastric carcinoma or gastric adenocarcinoma, respectively. The risk was 1.59 (95% CI, 1.10-2.16) in offspring whose diagnosis was at ages older than 50 years. Offspring risk from parental corpus carcinoma was of borderline significance whereas that from cardia carcinoma was below unity. The sibling risk for gastric carcinoma was 3.16 (95% CI, 1.35-5.72) and 5.75 (95% CI, 2.07-11.26) when diagnosed before age 50. The population attributable proportion of familial gastric carcinoma was 0.45%. Risks for second gastric carcinomas were increased in men and women after esophageal and skin carcinomas, and after non-Hodgkin lymphoma. CONCLUSIONS: The data suggest that environmental factors, perhaps Helicobacter pylori infections are the main reason for familial clustering of gastric carcinoma. The population attributable proportion of familial gastric carcinoma is much lower than that cited in the literature. The patterns of multiple carcinomas suggest that immunologic factors modulate susceptibility to gastric carcinoma.     

Parental lung cancer as predictor of cancer risks in offspring: Clues about multiple routes of harmful influence?

The carcinogenic effects of active smoking have been demonstrated for many sites, but the effects of passive smoking and exposures during pregnancy and breastfeeding are less well documented. We examined whether 0-70-year-old offspring of parents with lung cancer are at a risk of cancer that cannot be explained by their smoking or familial risk. It was assumed that known target sites for tobacco carcinogenesis would be affected, if any. The nationwide Swedish Family-Cancer Database with cancers recorded from 1958 to 2002 was used to calculate age-specific standardized incidence ratios (SIRs). Among offspring of affected mothers, increased risks were observed for upper aerodigestive (SIR 1.45), nasal (2.93), lung (1.71) and bladder (1.52) cancers and for kidney cancer (6.41) in one age group. The risk of bladder cancer was found in younger age groups than that of lung cancer. Cancers at many of these sites, but not the kidney or the bladder, were in excess in offspring of affected fathers. Nasal cancer was even increased when either parent was diagnosed with lung cancer; the highest risk was for nasal adenoid cystic carcinoma (7.73). The data suggest that passive smoking during childhood is associated with an increase risk of nasal cancer. For bladder and kidney cancers, a contribution by tobacco carcinogens is implicated through breastfeeding and in utero exposure.