Increased cancer risk among relatives of nonsmoking lung cancer cases

Lung cancer has been shown to aggregate in families of nonsmoking lung cancer cases with an earlier age at onset. The current study evaluates whether relatives of nonsmoking lung cancer cases are at increased risk of cancers at sites other than lung. Families were identified through 257 population‐based, nonsmoking lung cancer cases and 277 population‐based, nonsmoking controls residing in metropolitan Detroit. Data were collected for 2,252 relatives of cases and 2,408 relatives of controls. First‐degree relatives of nonsmoking lung cancer cases were at 1.52‐fold (95% CI, 1.02–2.27) increased risk of cancer of the digestive system after adjustment for each relative's age, race, sex, and smoking status. Relative risk estimates also were elevated, but not significantly, for tobacco‐related cancers (RR = 1.39) and breast cancer (RR = 1.72). Among first‐degree relatives of younger probands (age 40–59), risk was non‐significantly increased 72% (95% CI 0.95–3.10) for all cancers combined and 3.14‐fold for cancers of the digestive system (95% CI 0.76–12.9). Nonsmoking relatives of cases were at increased risk of all cancer sites combined (RR = 1.32; 95% CI 1.003–1.73), cancers other than lung (RR = 1.37; 95% CI 1.03–1.82), and digestive system cancers (RR = 2.01; 95% CI 1.20–3.37). These findings of moderate familial aggregation for cancers of the lung, digestive system, breast, and tobacco‐related sites suggest that common susceptibility genes may act to increase risk for a variety of cancers in families. Genet. Epidemiol. 17:1–15, 1999. © 1999 Wiley‐Liss, Inc.     

Heterogeneity of breast cancer risk in families of young breast cancer patients and controls.

Familial heterogeneity of breast cancer risk was assessed among 4,159 first-degree female relatives of 1,074 population-based, young breast cancer cases (aged 20-54 years) diagnosed from December 1, 1980 to December 31, 1982 and 4,120 first-degree female relatives of 998 age- and race-matched, population-based controls from the metropolitan Detroit, Michigan, area. The family risk index method used for analysis considers family size, age, and race differences among families in the assessment of family risk. Families of cases showed a higher risk of breast cancer than did families of controls, with case families 1.80 to 4.24 times more likely to be defined as high risk than control families; the magnitude of the risk differential was dependent on the definition of high risk. Within the case families only, familial heterogeneity of risk was suggested, with a small proportion of families (less than 5%) at lower risk of breast cancer than most case families. A number of reproductive risk factors, age, race, and histologic type of cancer for the proband, and several family characteristics were investigated to help characterize the case families at higher and lower risk.     

Aggregation of ovarian cancer with breast, ovarian, colorectal, and prostate cancer in first-degree relatives

Epidemiologic studies have demonstrated a tendency for common cancers to aggregate in families. The authors investigated the effects of family history of cancer at multiple sites, including the breast, ovary, colorectum, and prostate, on ovarian cancer risk among 607 controls and 558 ovarian cases in Hawaii and Los Angeles, California, in 1993-1999. A family history of cancer of the breast, ovary, colorectum, or prostate in first-degree relatives was associated with an increased risk of ovarian cancer (odds ratio (OR)=1.7, 95% confidence interval (CI): 1.1, 2.6; OR=3.2, 95% CI: 1.3, 7.9; OR=1.5, 95% CI: 0.9, 2.5; and OR=1.6, 95% CI: 1.0, 2.8, respectively). A greater risk of ovarian cancer was observed for women with parents rather than siblings with a history of breast or prostate cancer and for women with parental colorectal cancer diagnosed at an early age, suggesting a genetic predisposition among these women. The risk of nonmucinous tumors, but not mucinous tumors, was positively associated with a family history of cancer. No significant interaction effects on risk existed between oral contraceptive pill use or pregnancy and family history of breast and/or ovarian cancer. Study findings suggest that ovarian cancer aggregates with several common cancers in family members.     

Association between family history of cancer and breast cancer defined by estrogen and progesterone receptor status

There are recent data to suggest that risk factors for breast cancer may differ according to whether the tumor expresses detectable levels of the estrogen receptor (ER) and progesterone receptor (PR). While a family history of breast cancer is one of the most consistent predictors of the disease, we recently reported a modest inverse association with ER+PR− tumors. However, the definition of a family history of cancer did not consider second-degree relatives or cancer sites that may be etiologically related. The current report presents additional data analysis from the Iowa Women's Health Study, a prospective population-based cohort study conducted among 41,837 postmenopausal women. At baseline in 1986, respondents provided information on family history of cancers of the breast, ovaries, or uterus/endometrium in their mothers, sisters, daughters, maternal and paternal grandmothers, and maternal and paternal aunts. Data on family history of prostate cancer in fathers and brothers and age at onset of breast cancer in mothers and sisters were collected in 1992. Cohort members were followed for cancer incidence through the statewide tumor registry. After 7 years and more than 235,000 person-years of follow-up, 939 incident cases of breast cancer were identified. Information was obtained from the tumor registry on ER (+/−) and PR (+/−) status for 610 cases (65.0%). A family history of breast cancer in first-degree relatives was associated with increased risk (relative risk [RR] = 1.4; 95% confidence interval [CI]: 1.1–1.6) for all receptor-defined subtypes of breast cancer except ER+PR− tumors (RR = 0.7; 95% CI: 0.3–1.4). These results were unchanged when data on second-degree relatives were included. When the onset of breast cancer in relatives occurred at or before the age of 45 years, increased risks were evident only for ER−PR+ and ER−PR− tumors (RR = 2.3 and 3.3, respectively). Conversely, when relatives were affected with breast cancer after the age of 45 years, increased risks were most apparent for ER+PR+ and ER−PR+ tumors (RR = 1.3 and 3.2, respectively). A family history of prostate cancer in first-degree relatives was associated with a 1.2-fold increased risk of breast cancer (95% CI: 0.98–1.50), largely a reflection of the association with ER−PR− tumors (RR = 1.5; 95% CI: 0.8–3.0). The small numbers of cases in some categories and the corresponding wide CIs preclude definitive conclusions, but these data are at least suggestive that joint stratification of breast tumors on ER and PR status may be useful in partitioning breast cancer families into more homogeneous subsets. © 1996 Wiley-Liss, Inc.     

Familial risk of colo-rectal cancer in a low incidence area in Southern Italy

The risk of colo-rectal cancer (CRC) in subjects with a positive family history (FH+) for malignancy has been assessed by means of a case-control study carried out between 1987–89 in an area of about 215,000 inhabitants in Southern Italy. One hundred and nineteen CRC cases were compared with 119 sex - and age - frequency matched population controls. Detailed pedigrees were collected at the family homes of both cases and controls. The odds ratio (OR) of CRC, adjusted by means of logistic regression for age, sex and number of first-degree relatives, increased with the number of any kinds of cancers in first-degree relatives with a significant linear trend (p = 0.042), while there was no risk with a FH+ for digestive cancer excluding CRC or for other cancers excluding large bowel and digestive organs. The OR (and 95% confidence interval) for CRC was 5.9 (1.64–21.23) for at least one first-degree relative with CRC. After a mutual adjustment between CRC and the other cancers in the families of cases and controls, the risk of CRC with a FH+ for other cancers did not change, revealing a strong association (p = 0.002) for CRC alone. From the analysis of the family history of cancer in the case group, the relative frequency of families that satisfied the criteria for so-called hereditary non-polyposic colo-rectal cancer (HNPCC) was 2.6%. The increased relative risk of CRC observed only in families with FH+ for CRC is a supportive finding for organizing and planning prevention and genetic counselling for these families, whose members should be referred for further assessment.     

Association of parity and ovarian cancer risk by family history of breast or ovarian cancer in a population-based study of postmenopausal women.

Although parity is associated with a decreased risk of ovarian cancer in the general population, this association among women with a family history is less clear. We examined this question in a prospective cohort of 31,377 Iowa women 55-69 years of age at baseline. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated through Cox regression. We identified 181 incident epithelial ovarian cancers through 13 years of follow-up. At baseline, 14% of the women reported breast or ovarian cancer in a first-degree relative, and an additional 12% reported a family history in a second-degree relative. Among women without a family history of breast or ovarian cancer in a first-degree relative, nulliparous women were at slightly increased risk of ovarian cancer (RR = 1.4, 95% CI = 0.9-2.4) compared with parous women, whereas among women with a family history, nulliparous women were at a much higher risk (RR = 2.7, 95% CI = 1.1-6.6) than parous women. Similar results were seen when family history included first- or second-degree relatives with breast or ovarian cancer or a first- or second-degree relative with ovarian cancer only. Nulliparity may be more strongly associated with an increased risk of ovarian cancer among women with a family history of breast or ovarian cancer, compared with women who do not have a family history of those cancers.     

The genetic epidemiology of second primary breast cancer.

It is well established that women with a family history of breast cancer run a higher risk of breast cancer than do women without a family history. The evidence, however, is less clear regarding a possible association between a family history of breast cancer and risk of second primaries. The purpose of this prospective study was to estimate the risk for second primary breast cancer associated with having a family history of breast, endometrial, and ovarian cancers. A cohort of 4,660 women with a first primary breast cancer diagnosed between 1980 and 1982 were interviewed as part of the Cancer and Steroid Hormone Study, a multi-center population-based case-control study, and followed through eight Surveillance, Epidemiology, and End Results (SEER) program registries for 4 to 6 years. Of these women, 136 developed a second primary breast cancer in the contralateral breast at least 6 months after diagnosis of the first primary. Cox proportional hazards modeling techniques were used to model the time to onset of second primary breast cancer while adjusting for multiple predictors. The risk of contralateral breast cancer was elevated among cohort members who reported a history of breast cancer in a first-degree relative (multivariable-adjusted rate ratio (RR) = 1.91, 95% confidence interval (CI) = 1.22-2.99). Early age at onset (< 46 years) in the relative further increased the risk of developing contralateral breast cancer (sister: multivariable-adjusted RR = 3.36, 95% CI 1.62-6.98; mother: multivariable-adjusted RR = 2.35, 95% CI 1.02-5.43). Bilateral breast cancer in mothers was also associated with more than a two and a half-fold increase in risk (multivariable-adjusted RR = 2.55, 95% CI 1.02-6.35). The association between family history of breast cancer and risk of contralateral breast cancer did not vary substantially according to age at onset of the first primary breast cancer. The age-adjusted rate ratio for development of a second primary breast cancer among women with a first-degree relative with endometrial cancer was 2.13 (95% CI 1.04-4.35), while the corresponding rate ratio among women with a family history of ovarian cancer was 1.69 (95% CI 0.42-6.83). There was little evidence that age at onset among the relatives with endometrial or ovarian cancer affected the risk. Some of these findings have not been previously reported and need replication in future studies.     

Family history of cancer and incidence of acute leukemia in adults

Family history of cancer may represent shared genetic and environmental risk factors for leukemia. The authors examined associations of first-degree family history of cancer with adult acute leukemia incidence by using data on 811 patients (or their proxies) identified at diagnosis and 637 population-based controls in the United States and Canada during 1986-1990. For proxy-interviewed patients, relative risks were elevated for family history of any cancer (relative risk = 1.7, 95% confidence interval (CI): 1.3, 2.4), hematopoietic cancer (relative risk = 1.8, 95% CI: 1.1, 3.0), leukemia (relative risk = 2.4, 95% CI: 1.3, 4.6), and breast cancer (relative risk = 1.7, 95% CI: 1.0, 3.0) but not for colorectal, prostate, or lung cancer. For self-interviewed patients, family history of hematopoietic cancer was inversely associated with leukemia incidence (relative risk = 0.6, 95% CI: 0.4, 1.1). Regardless of patient interview type, history of breast cancer in sisters was positively associated with adult acute leukemia, whereas history of breast cancer in mothers was not. The role of family history of cancer in leukemia etiology is unclear because of differential reporting by patients and proxies. Specifically, self-interviewed patients may underreport cancer in their first-degree relatives. Associations between family history of breast cancer and leukemia incidence may be the result of unmeasured, shared etiologies specific to these cancers.     

Validation of family history data in cancer family registries

BACKGROUND: Although family history information on cancer is used to infer risk of the disease in population-based, case-control, cohort, or family-based studies, little information is available on the accuracy of a proband's report. In this study, we sought to determine the validity of the reporting of family history of cancer by probands in population-based and clinic-based family registries of breast, ovarian, and colorectal cancers. METHODS: To assess the accuracy of probands' reported family history of cancer in their relatives, we compared the family history from the personal interview of each proband to a reference standard that included pathology reports, self-reports, or death certificates on the relatives. Our study included 1111 families that accounted for 3222 relatives who were verified. To account for within-family correlations in the responses, we used a generalized estimating equation approach. RESULTS: The probability of agreement between the proband-reported cancer status in a relative with the reference standard varied by cancer site and by degree of relationship to the proband. This probability for first-degree relatives was 95.4% (95% confidence interval [CI]=92.6-98.3) for female breast cancer; 83.3% (95% CI=72.8-93.8) for ovarian cancer; 89.7% (95% CI=85.4-94.0) for colorectal cancer; and 79.3% (95% CI=70.0-88.6) for prostate cancer. CONCLUSIONS: We found high reliability of probands' reporting on most cancer sites when they reported on first-degree relatives and moderate reliability for their reporting on second- and third-degree relatives. Overreporting of cancer was rare (2.4%). Race or ethnicity and gender of the proband did not influence the accuracy of reporting. However, degree of relationship to the proband, type of cancer, age at diagnosis of the proband, and source of ascertainment of probands were statistically significant predictors of accuracy of reporting.     

Age at onset as an indicator of familial risk of breast cancer

The familial risk of breast cancer was investigated in a large population-based, case-control study conducted by the Centers for Disease Control. The data set included 4,730 histologically confirmed breast cancer cases aged 20-54 years and 4,688 controls who were frequency matched to cases by geographic region and 5-year categories of age. Family history of breast cancer among first-degree female relatives of cases and controls was utilized. To identify factors associated with familial risk of breast cancer, a Cox proportional hazards model was used, modeling time to onset of breast cancer among mothers and sisters. Case relatives were at greater risk than control relatives. Among relatives of cases, a significant increase in the risk of breast cancer was associated with decreasing age at onset of the case and with having an additional relative affected with breast cancer. The hazard ratio for the mother of a case with breast cancer diagnosed at 50 years of age was 1.7 (95% confidence interval (Cl) 1.4-2.0), compared with 2.7 (95% Cl 2.2-3.2) and 4.3 (95% Cl 3.3-5.6) for the mother of a case whose diagnosis occurred at 40 and 30 years of age, respectively. The hazard ratio for the sister of a case with an unaffected mother and at least one affected sister in addition to the case was 3.6 (95% Cl 2.1-6.1) when the case was diagnosed at age 50, compared with 5.8 (95% Cl 3.4-10.0) and 9.4 (95% Cl 5.3-16.7) when the case was diagnosed at 40 and 30 years of age, respectively. The hazard ratio for the sister of a case with an affected mother and no additional affected sisters was 5.9 (95% Cl 3.9-8.9) when the case was diagnosed at age 50, compared with 9.4 (95% Cl 6.2-14.4) and 15.1 (95% Cl 9.4-24.3) when the case was diagnosed at 40 and 30 years of age, respectively. The hazard ratio for the sister of a case with both an affected mother and at least one affected sister aside from the case was 17.1 (95% Cl 9.4-31.3) when the case was diagnosed at age 50, compared with 27.5 (95% Cl 15.0-50.3) and 44.2 (95% Cl 23.5-83.2) when the case was diagnosed at 40 and 30 years of age, respectively. No effect of case's menopausal status and bilaterality was found, indicating that in addition to a positive family history, age at onset is the strongest indicator of a possible genetic subtype of breast cancer in these data.     

Increased familial risk for non-lung cancer among relatives of lung cancer patients

Reports of two or more anatomically distinct cancer types clustering in families suggest the possible existence of a susceptibility-to-cancer gene. To determine whether a genetic predisposition accounts for such familial aggregation, a retrospective case-control study was conducted in 1976-1979 of 337 southern Louisiana families in each of which a deceased lung cancer patient was used as the proband. A comparison of first-degree relatives of proband families with spouse (control) families revealed a significantly greater overall risk of cancer (odds ratio (OR) = 2.0, p less than 0.0001) in the proband group. Using logistic regression techniques to control for the confounding effects of age, sex, cigarette smoking, and occupational/industrial exposures, relatives of lung cancer probands maintained an increased risk of non-lung cancer (p less than 0.05). The crude odds ratio of a proband family having one family member with cancer was 1.67 compared with control families. Proband families were 2.16 times more likely to have two other family members with cancer. For three cancers and four or more cancers, the risk increased to 3.66 and 5.04, respectively. Each risk estimate was significant at the 0.01 level. The most striking differences in cancer prevalence between proband and control families were noted for cancer of the nasal cavity/sinus, mid-ear, and larynx (OR = 4.6); trachea, bronchus and lung (OR = 3.0); skin (OR = 2.8); and uterus, placenta, ovary, and other female organs (OR = 2.1). These data support the hypothesis of a genetic susceptibility to cancer in families with lung cancer.     

Relationship of epithelial ovarian cancer to other malignancies within families

The relationship of family history of cancer of the breast, colon/rectum, cervix, endometrium, lung, and thyroid to the risk of epithelial ovarian cancer was investigated in a large population-based case-control study. The data consisted of family histories from 493 epithelial ovarian cancer cases and 2,465 controls aged 20-54 years. After controlling for potential confounders, risk for epithelial ovarian cancer was found to be significantly elevated among women reporting breast cancer and colo/rectal cancer in a first-degree relative. Adjusted odds ratios were 1.5 (95% CI = 1.1-2.1) and 1.9 (95% CI = 1.1-3.3), respectively. None of the remaining four types of cancer was found to be statistically associated with the risk of epithelial ovarian cancer. However, when histologic subtypes of epithelial ovarian cancer were considered, a family history of breast cancer was found to be associated with an elevated risk of endometrioid ovarian cancer (odds ratio = 2.3; 95% CI = 1.1-4.7), as was a family history of endometrial cancer (odds ratio = 2.7; 95% CI = 1.0-6.9). The results are considered in the context of other studies of familial patterns of cancer and are compared with published findings concerning the occurrence of multiple primary cancers in the same individual. The findings indicate that further study is warranted regarding possible genetic relationships between epithelial ovarian cancer and cancers arising in other organs.     

京、津、沪、渝四城市肺癌危险因素病例对照研究

目的 分析肺癌危险因素,探讨监测指标。方法 利用《常见恶性肿瘤发病,死亡及危险因素监测方法研究》课题第１次现场调查中京、津沪、渝四市城区病例对照调查资料,运用多因素条件ｌｏｇｉｓｔｉｃ回归分析方法。结果 在调整年龄、受教育程度、人均月收入和控制其他因素作用的基础上,吸烟（ＯＲ＝３．４６）、体质指数小（ＯＲ＝１．１８）,长期精神压抑（ＯＲ＝２．６４）、情绪调节能力差（ＯＲ＝２．７１）,既住呼吸系疾病     

Cancer risk assessment: quality and impact of the family history interview

BACKGROUND: Identification of individuals at high risk for colon and breast cancer requires an adequate family history assessment and can influence cancer screening and genetic testing decisions. Little data exist that evaluate the completeness of the family history interview in primary care. METHODS: Retrospective chart review of 995 new patient visits to 28 primary care physicians evaluating the completeness of the family cancer history for colon or breast cancer. Family history information was evaluated for inclusion of age at diagnosis, degree of kinship, and specification of disease of interest. RESULTS: Family history information on cancer diagnoses was collected on 679 (68%) of the patients. Specific information regarding the individual affected and the cancer diagnosis was present in 414 (61%) of the records. Affected first-degree relatives were more likely to have their age of cancer diagnosis recorded than second-degree relatives (39%, 95% confidence interval [CI]=34%-44% vs 16%, 95% CI=12%-20%). Age at diagnosis of cancer in first-degree relatives was documented in 51% of colon cancers, 38% of breast cancers, and 27% of ovarian cancers. Only 17% of individuals who meet criteria for early-onset breast cancer genetic testing were referred for genetic services. CONCLUSIONS: Adequate cancer risk assessment using family history information requires age at cancer diagnosis and specification of a cancer diagnosis. Age at diagnosis was frequently missing from family history assessments, which could have a potential impact on identification of high-risk individuals. When family history information does identify high-risk individuals, only the minority are referred for genetic services.     

Familial factors associated with malignant gliomas

Family histories of male patients with histologically confirmed malignant gliomas were compared to family histories of controls (wives). Included were 77 case families with 892 relatives and 77 control families with 719 relatives. Cases had significantly more siblings than controls (P = 0.02), although cases were not preferentially the oldest or the youngest sibs. Odds ratios of two or more were found for mental retardation, Parkinson's disease, and meningitis for the relatives of cases versus controls, but none were statistically significant. The excesses of Parkinson's disease and meningitis were explained by the family of one particularly interesting case containing three relatives with meningitis and two relatives with Parkinson's disease. Noteworthy age-adjusted odds ratios for cancer among relatives of cases compared to relatives of controls were 1.6 (95% confidence interval (CI) = 1.0-2.3) for cancer of any site, 2.4 (95% CI = 0.8-6.1) for breast cancer, and 4.0 (95% CI = 0.6-10.7) for lung cancer. Only the odds ratio for cancer of any site was statistically significant. Overall, 6 of 77 (8%) of cases came from families that included two or more relatives with breast or lung cancer in addition to the proband with malignant glioma. These three cancer sites may form familial clusters worthy of further evaluation in future studies by pedigree and genetic linkage analyses.     

Breast cancer risk factors among black women and white women: similarities and differences.

To further explore whether breast cancer risk factors are the same for black women and white women, the authors investigated several biologic, cultural, and social factors in a 1980-1982 case-control study of non-Hispanic black subjects (490 cases, 485 controls) and non-Hispanic white subjects (3,934 cases, 3,901 controls) aged 20-54 years. Logistic regression analyses indicated that blacks and whites shared four risk factors at a comparable magnitude (age at first full-term birth, parity, surgical menopause, and history of benign breast disease). For two observed risk factors, the magnitude (breast feeding) and pattern (family history of breast cancer) of the relation were different in blacks and whites. The relative risks of breast cancer among black women who had first-degree relatives (odds ratio (OR) = 1.61) and second-degree relatives (OR = 1.71) with breast cancer were similar, whereas the relative risk among white women who had first-degree relatives (OR = 2.16) was distinctly larger than for those who had second-degree relatives (OR = 1.44) with breast cancer. The relation of early age at menarche appeared negligible for blacks although significant for whites aged 12 and under (OR = 1.26). The results also indicated that natural menopause, oral contraceptive use, and cigarette smoking may have different, and more complex, relations to breast cancer among blacks and whites.     

Evidence for age-specific genetic relative risks in lung cancer

Recent studies of familial aggregation suggest that family history of lung cancer among first-degree relatives is associated with increased risk for early-onset, but not late-onset, lung cancer. To assess whether this could be explained by variability in genetic relative risk across age, segregation analysis was performed on the Louisiana Lung Cancer Dataset. This data set consisted of 337 probands who died of lung cancer between 1976 and 1979 and their first-degree relatives. A variation of the Cox proportional hazards model was used that allowed estimation of age- and genotype-specific incidence rates, from which the authors obtained estimates of age-specific genetic relative risks. The best-fitting model included an autosomal dominant locus (allele frequency, 0.043), with carrier-to-noncarrier relative risks that exceeded 100 for ages less than 60 years and declined monotonically to 1.6 by age 80. The hypothesis of proportional genetic relative risk across age was rejected (p = 0.009). The estimated proportion of persons with lung cancer who carry the high-risk allele exceeds 90% for cases with onset at age 60 years or less and decreases to approximately 10% for cases with onset at age 80 years or older. These findings support previous evidence of a major susceptibility locus for lung cancer and suggest that linkage studies should preferentially recruit young lung cancer cases and their relatives.     

Nonfatal cancer preceding Parkinson's disease: a case-control study

BACKGROUND: We conducted a population-based case-control study to investigate the association of Parkinson's disease (PD) with preceding nonfatal cancer. METHODS: We used the medical records-linkage system of the Rochester Epidemiology Project to identify all incident cases of PD in Olmsted County, MN (1976-1995). Each case was matched by age and sex to a general population control. We ascertained cancer diagnoses through medical records abstraction. RESULTS: The frequency of any cancer was lower in cases (19.4%) than in controls (23.5%) (OR = 0.79; 95% CI = 0.49-1.27). This pattern was more pronounced in women than in men, and in patients age 71 years or younger at onset of PD than in older patients. We found an interaction between smoking and smoking-related cancers in their association with PD. Bladder cancer (OR = 0.22; 95% CI = 0.03-2.24) and breast cancer (OR = 0.20; 95% CI = 0.02-1.71) were less frequent in PD cases than in controls, whereas prostate cancer was more frequent in PD cases than in controls (OR = 1.80; 95% CI = 0.60-5.37). However, these results are based on small numbers. CONCLUSIONS: We did not find a strong association between PD and preceding nonfatal cancer. There were suggestive trends in analyses stratified by sex and age at onset of PD, and for specific cancers related to smoking or hormonal factors.     

Lung cancer risk associated with cancer in relatives

Family history data from an incident case-control study of lung cancer conducted in the Texas Gulf Coast region between 1976 and 1980 were analyzed to evaluate the contribution of cancer in first-degree relatives to lung cancer risk. Odds ratios (OR) increased slightly as the number of relatives with any cancer increased (reaching 1.5 with 4 or more relatives with cancer). Risks were higher for tobacco-related cancers (OR = 1.5 for 2 or more relatives with these tumors) and greatest for first-degree relatives with lung cancer (OR = 2.8 for lung cancer in 2 or more relatives). For cases of squamous cell carcinoma and adenocarcinoma of the lung, risks with 3 or more relatives with any cancer were increased 2-fold (OR = 1.8 and 1.9 respectively), and a significantly elevated risk was found for having a first-degree relative with lung cancer for each histologic type (ORs from 1.7-2.1). Having a spouse with lung cancer increased lung cancer risk (OR = 2.5), and cases with lung cancer reported in a first-degree relative were diagnosed at an earlier age, as were case siblings with lung cancer.     

Benign breast disease among first-degree relatives of young breast cancer patients

Benign breast disease is associated with increased risk of breast cancer. To further clarify whether there is a genetic link between benign and malignant breast lesions, the authors identified 14,648 first-degree female relatives of 8,807 patients in whom breast cancer was diagnosed at <50 years of age by using Danish nationwide cancer and population registers. Hospital register data were used to follow the relatives for occurrence of benign breast disease from 1977 to 2003 and to calculate rates of benign breast disease in the general population of Danish women for comparison. Risk for relatives was increased for benign breast diseases (observed/expected ratio = 1.54, 95% confidence interval: 1.42, 1.66), particularly for relatives aged <40 years. Higher risks were observed after breast cancer had been diagnosed in the family; however, an increased risk for relatives aged <50 years (observed/expected ratio = 1.24, 95% confidence interval: 1.02, 1.51) was present before breast cancer was diagnosed in the family. Enhanced surveillance of close relatives of breast cancer patients seems to be an important factor to address when investigating the association between benign breast disease and familial breast cancer. A genetic link between benign breast disease and breast cancer was indicated by our data but needs to be confirmed in future studies.