Coherence and Completeness of Population-based Family Cancer Reports

Introduction

Family history of cancer is a major risk factor for many malignancies (1), functioning as a surrogate for genetic susceptibility to disease, or high-risk behaviors and environmental exposures that cluster within families. Family history is obtained in widely varying degrees of detail in both clinical and population-based cancer research. In clinical care, family history of cancer is used to make recommendations for screening (2-4), genetic counseling referrals, genetic testing, and risk-reducing interventions (5-8).

Routine family history assessment has been proposed as a public health tool for risk stratification of primary care populations to tailor clinical interventions, such as cancer screening and genetic counseling referrals, and to motivate risk-reducing behaviors (9-12). In 2004, the U.S. Surgeon General's Family History Initiative was launched to promote awareness and ascertainment of family history information (13). In public health surveillance, family history information is periodically collected in population-based surveys, such as the National Health Interview Survey (NHIS) in 2000 and 2005 (14), the California Health Interview Survey in 2001 and 2005 (15), and various state surveys in the Behavioral Risk Factor Surveillance System (16). Family history variables can be used for estimating population prevalence of familial risk, stratifying health and behavior outcomes, and planning for allocation of preventive resources. For example, Ramsey et al. (17) used 2000 NHIS data to estimate the U.S. population prevalence of family history of breast, colorectal, lung, prostate, and ovarian cancer.

Methodologic research suggests that the quality and utility of family history of cancer are highly variable (18-20). Overall, validation of data collection instruments has been limited (21). Studies comparing self-reports against medical records indicate that accuracy varies by cancer site and the characteristics of the reporting family member (17, 22, 23). Because little is known about the qualitative characteristics of self-reported family histories and the types of reporting error, particularly in general population samples, methodologic research in this area may help improve family history assessment in primary care.

In 2001, we conducted a random digit dial survey in Connecticut to ascertain reports of family history of cancer in a general population household survey. This study describes the coherence and completeness of such reports in a unique, population-based sample of 1,019 survey respondents who reported cancer histories for 20,504 biological relatives. Multivariate models are presented that identify demographic, sociologic, and medical characteristics associated with coherent reporting of specific cancer sites and general awareness of relatives' cancer histories. The implications for clinicians and researchers are discussed. Validity of the family histories will be reported elsewhere.

Results

Of the 1,019 respondents in the study, 8.3% (6.7-10.3%) reported a personal history of cancer and 82.8% (79.7-85.6%) reported at least one relative in the family ever diagnosed with cancer; 51.9% (48.4-55.5%) reported at least one FDR and 71.6% (68.1-74.8%) reported at least one SDR. A slightly higher percentage of respondents with a personal history than without also reported a family history, but the difference was not statistically significant (P = 0.54).

Consistency and Specificity of Family Cancer Reports

Respondents reported 2,657 cancers among the 2,408 total relatives with a positive cancer history. As shown in Table 1, 97.7% of all reports were judged to be consistent with malignancy. However, when the reports were classified into the five analytic categories, only 79.0% were both consistent and site specific, whereas 10.1% were consistent/unspecified site and 8.6% were consistent/ill-defined site. A nominal 1.3% of reports were classified as not consistent with malignancy and 1.1% were indeterminate. As described below, these percentages varied significantly (P < 0.0001) by kinship when the 918 cancer reports about FDR (n = 781) were compared with the 1,739 reports about SDR (n = 1,627).

Consistent/Site-Specific Reports

Overall, 86.6% of FDR reports were consistent/site specific compared with only 75.0% of SDR reports. Among the 2,110 total reports, the 10 most commonly reported sites were breast, lung, melanoma, prostate, colon/rectum, stomach, nonmelanoma skin cancer, leukemia, lymphoma, and brain, in decreasing order (data not shown).

Consistent/Ill-Defined or Unspecified Reports

As shown in Table 1, 8.6% of FDR reports were consistent with malignancy but had an ill-defined (6.5%) or unspecified cancer site (2.1%). In contrast, a much larger percentage (23.9%) of SDR reports were ill defined (9.7%) or unspecified (14.2%). Among the 225 ill-defined reports, the most common ambiguities were body regions or multiple organs mentioned instead of a single primary site. Forty percent of ill-defined reports were suggestive of digestive system cancers, including 13.3% that mentioned “abdomen” or “intestines” and 27.1% that mentioned other regions (“mouth,” “GI tract”), multiple organs with at least one in the digestive system (e.g., “either liver or kidney cancer”), or mixed organs and regions (e.g., “stomach or intestinal cancer”). Furthermore, 38% were suggestive of respiratory system cancers, including 25.3% that mentioned “throat cancer” and 12.9% that mentioned other regions (“chest”), multiple organs with at least one in the respiratory system (“larynx or esophageal”), or mixed organs and regions (“lung or throat”). The remaining ill-defined reports were diverse with regard to possible site of origin. In contrast to ill-defined reports, the 260 unspecified reports were too ambiguous to even suggest a body region or organ (e.g., “the cancer was all over by the time they found it”; “I don't know what kind of cancer it was”).

Table 2 shows combined percentages of ill-defined or unspecified reports by respondent and relative characteristics. After adjustment for covariates in the table, the percentage of FDR reports decreased with increasing educational level of the respondent (P = 0.005, test for trend). It also varied by respondent race/ethnicity (P = 0.008) and by relatives' vital status (P = 0.03), with pairwise comparisons showing higher percentages of ambiguous reports if respondents were African-American (versus white) or relatives were deceased (versus living). Percentages of ill-defined or unspecified reports about SDR varied significantly by respondent gender (P = 0.001) and relatives' vital status (P < 0.0001). In pairwise comparisons, higher percentages were observed if respondents were male or the relative's vital status was deceased or unknown.

Unknown Cancer Histories

The distribution of cancer history among the 20,504 relatives was based on answers to the question “Did he/she ever have cancer?” As expected in a general population sample (9), the large majority, 82.7%, had no reported history of cancer and 11.3% had a positive history. Only 6.1% had an unknown cancer history, although this proportion was substantially higher among SDRs (8.5%) than in FDRs (0.6%; P = 0.0005). In logistic regression analysis of all relatives combined, SDRs were significantly more likely to have an unknown cancer history than FDRs [7.0% (6.0-7.9%) versus 1.5% (1.0-1.9%), respectively] after adjustment for the characteristics in Table 3.

Table 3 shows percentages of relatives with an unknown cancer history (versus a reported positive or negative history) by respondent and relative characteristics. The percentage of FDR with unknown history decreased with increasing educational level of the respondents (P = 0.04, test for trend). It also varied by respondent race/ethnicity (P = 0.01), with respondents in the “other” category (i.e., Asians, Pacific Islanders, American Indians/Alaska Natives, mixed, and unknown) reporting significantly more unknown histories than whites. Unknown history further varied by relative vital status (P < 0.0001) and generation within the family structure (P = 0.0001). Specifically, the percentage with an unknown history was higher if the vital status was unknown (versus living) or the relative was one generation older (i.e., versus the same or of a younger generation).

A larger set of respondent characteristics was associated with unknown cancer history among SDRs, including gender (P = 0.002), main living arrangement of parents during childhood (P = 0.0004), personal history of cancer (P = 0.006), and education (P = 0.05), although no trends or significant pairwise differences were observed across educational levels. As with FDR, unknown cancer history varied by SDR vital status (P < 0.0001) and generation (P < 0.0001). In pairwise comparisons, the percentage of relatives with unknown cancer history was higher if respondents were male, had a personal history of cancer (versus none or an unreported history), or the parents had lived apart for most of the respondents childhood (versus together). It was also higher if relative's vital status was unknown or deceased or the relative was one or two generations older than the respondent.

Age at Diagnosis

Respondents were asked to provide age or year of diagnosis for all relatives' cancers except nonmelanoma skin cancers. Year of diagnosis was used to calculate age at diagnosis if birth year or current age was also provided. If unable to provide that level of detail, respondents were next asked for 10-year age or year ranges and whether the diagnosis was early, mid, or late within that range. If range was unknown, the respondent was asked whether the relative was “under age 50” or “50 or older” when diagnosed. Age at diagnosis was then estimated. For example, a cancer reported early in the 60-year age range was assigned a diagnosis age of 62, whereas a cancer reported as under age 50 was assigned age 45. Of 2,488 reports that were judged consistent with cancer (excluding the nonmelanoma skin cancers), 16% specified an age at diagnosis, 38% included a year, 42% provided a 10-year age or year range, 2% specified <50 or 50+ years old, and 2% had no information.

Discussion

This study characterized the completeness and coherence of family cancer history reports ascertained in a general population sample. Only 6.1% of relatives had a completely unknown cancer history, and there was little evidence of overreporting of other conditions as cancer. Eighty-three percent of respondents reported a positive history of cancer in at least one relative. However, only 79% of reports describing types of cancer diagnosed in relatives were judged to be fully coherent based on the dual criteria of consistency with malignancy and site specificity. Coherence of reports varied significantly in association with several covariates, discussed in greater detail below. These findings suggest that family history data may be sufficiently detailed to provide useful risk assessment in the primary care setting or to monitor familial risk patterns in population surveys. However, risk assessment may be hampered by ambiguous cancer site information in approximately one fifth of reported diagnoses.

Because the study questionnaire used an open-ended format to ascertain type of cancer, the responses were distributed across a qualitative continuum. There were three intermediate categories of reports in between the 79% fully coherent reports and the 1% indicative of indeterminate disease. The ill-defined reports mentioned body regions or several distinct organs, reflecting respondent uncertainty about the exact diagnosis. The unspecified reports lacked information about any possible site of origin, suggesting wider gaps in respondent knowledge, or perhaps some cases with disseminated disease at diagnosis where site of origin was not determined. Given that family history reports must be interpretable in the context of disease risk to have clinical utility (32), such reports would generally have little use in the clinical setting, where familial risk patterns are evaluated based on the specific cancer sites involved. The third intermediate category contained reports of nonmalignant diseases, indicating that some respondents held imprecise beliefs about what constitutes cancer. Although contradictory, these reports can still be useful for ruling out cancer.

Not surprisingly, both the coherence and completeness of family history reports, and respondent awareness that their relatives did or did not have cancer, varied by kinship and other factors that influence communication within families. A much greater percentage of ambiguous cancer reports concerned SDR, who also had more unknown cancer histories than FDR. Given that SDR outnumber FDR in almost all families (24) and information about them is generally of lower quality, the cost versus benefit of collecting SDR data warrants consideration in settings where its value may be limited. One consequence of not seeking SDR information is that cancer patterns suggesting an underlying hereditary susceptibility may be missed in small families with few at-risk FDRs (33). For example, in some families, it may be difficult to recognize paternally transmitted breast-ovarian cancer syndrome without SDR information. Thus, the decision of whether to seek information about SDR may vary depending on the cancer site of interest and what is known about its genetics.

Besides kinship, vital status of the relative was the only variable consistently associated with both ill-defined or unspecified cancer reports and unknown cancer history. After adjustment for vital status, unknown cancer history among SDRs was further associated with older generations and with parental separation during the respondent's childhood. Encouraging individuals to communicate with “family gatekeepers” who possess detailed information about the larger pedigree may improve family history ascertainment for deceased or older generations of SDR. Our findings support the need for initiatives, such as the Surgeon General's Family History Initiative (13), to encourage people to learn more about, and maintain records of, their family health history.

Demographic characteristics of respondents were another major source of variation in the coherence and completeness of family history of cancer reports. Lower educational attainment was positively associated with ill-defined or unspecified cancer reports in relatives, and with unknown cancer history in each kinship group, suggesting less awareness or perceived benefit of family history information among respondents from lower socioeconomic subgroups. Male gender of the respondent was also associated with ill-defined or unspecified cancer reports, and unknown cancer history, but only among SDRs. Other studies have found underreporting of family history of common cancers by men (34, 35), possibly attributable to cultural practices favoring women as family gatekeepers. Our data suggest that men may provide coherent family history of cancer information for their closest relatives.

After adjustment for education and all other factors, African-Americans were more likely to report ill-defined or unspecified cancers than whites, although these estimates were unstable due to small sample size. This may partly reflect limited cancer information sharing within families (34, 36, 37), fewer inquiries about family history from health care providers (38), or less awareness of paternal family history (39). Findings that coherence and completeness of reports vary significantly by demographic features of respondents suggest that interventions to promote family history taking should be tailored to the educational and cultural characteristics of population subgroups (40, 41).

In this study, 8.3% of respondents reported a personal history of any cancer, including nonmelanoma skin cancer. This was higher than a published national estimate of 4.8% from the NHIS that excluded nonmelanoma skin cancers (42). We used 2001 NHIS data (14) to obtain an estimate that, like our survey, restricted respondent ages to 25 to 64 years and included all skin cancers. The resulting estimate of 5.1% was still lower than 8.3%, perhaps reflecting true differences between Connecticut and the United States overall or reporting errors in both surveys. Unexpectedly, unknown cancer among SDRs was significantly higher if respondents reported a personal history of cancer, and a nonsignificant increase was also observed among FDRs. We would expect respondents with a personal history to have greater awareness of relatives' diagnoses or to have a similar awareness as those without a personal history if their diagnosis was simply nonmelanoma skin cancer. This counterintuitive finding may be partly explained by misclassification of respondents with regard to their personal cancer history. For example, family history knowledgeable respondents may have underreported their personal history, and also, 7 of the 96 who did report a personal history actually mentioned nonmalignant diagnoses. Awareness may have been further tempered by the fact that 25 of them only reported nonmelanoma skin cancers.

Respondents were able to provide a year or age of diagnosis for relatives' cancers in a slim majority of cancer reports (54%). By further probing, using 10-year age ranges, and where appropriate, about a diagnosis age of <50 or ≥50, we were able to estimate age for an additional 44% of relatives. This type of probing offers an easy, low-cost strategy to obtain an estimate of age at diagnosis for the cancer reports.

Specific strengths of this study include the population-based sample design that likely approximates primary care populations in demographics and the high prevalence of average to moderate cancer risk. Therefore, our results can shed light on potential barriers to and facilitators of family history ascertainment in primary care practice settings, where such information is of increasing interest for risk assessment and personalized preventive care (19, 42, 43). The open-ended format of the family history questions in the survey instrument was an additional strength. Although this format is not necessarily cost-effective in studies seeking limited family history data, it enabled us to conduct a qualitative evaluation of the full range of verbatim responses. It is not well understood which if any kinds of family history questions or advance materials ultimately yield less ambiguous and more accurate responses.

There are several limitations to this study. First, the results may not be generalizable to ineligible subgroups of respondents, such as those <25 or >64 years old or immigrants. In one national survey, the latter were one third as likely to report any family history of cancer than U.S.-born respondents (44), suggesting that our prevalence estimate of any family cancer history might have been substantially lower had immigrants been included. Furthermore, because the Connecticut sampling frame and study sample had greater proportions of whites and people with higher income and education than the U.S. population (24), the coherence and completeness of family history reports may be overestimated relative to the United States overall or to populations with different demographic characteristics. The number of Hispanics and other minority groups was small, resulting in unstable estimates of ambiguous cancer reports and unknown cancer histories. Preinterview family history ascertainment by respondents whose households received advance recruitment materials, and inadvertent overinterpretation of verbatim reports by interviewers, may have also caused some overestimation. In addition, this analysis used data from a follow-up interview (because respondent demographic data were not obtained in the baseline interview several weeks earlier), and it is possible that differential loss of respondents with less family history awareness introduced some bias.

An additional caveat is that study conclusions can only be drawn about the interpretive value of family history reports and not about their accuracy, as the latter was not evaluated in the present analysis and will be reported elsewhere. However, the distribution of reported cancers did show consistency with other studies: for example, four of the five most common cancers in family members (i.e., breast, lung, colorectal, and prostate) were also reported as the top four in a cancer screening trial of 149,332 participants in 10 U.S. locations (35) and in the 2000 NHIS (17). Although our survey was conducted in 2001, we are not aware of time trends that would render these results obsolete; in fact, our telephone response rates may have been higher than what could now be achieved (45). Finally, the ability to draw conclusions about childhood cancers is somewhat limited because respondents' grandchildren were excluded from ascertainment (although childhood cancers were ascertained from included relatives).

In primary care settings, recording and use of family health information may be limited by time or other considerations (18, 44, 46). Therefore, data collection tools that enable patients to record family histories on their own time and transfer the information to their clinicians are potentially very useful. In recent years, several computerized tools have been developed to support family history ascertainment in broad populations (23). Public use software, such as My Family Health Portrait, CDC Family Healthware, and others (47-49), aim to promote and facilitate patient- and consumer-based collection of family history information for risk assessment and health promotion purposes. Recent progress has been made toward standardizing core family history information to integrate into electronic health records (50). The identification of five qualitative categories of cancer reports in this study provides a conceptual framework for designing such tools in ways that help shift the distribution of cancer responses toward consistency and site specificity. For example, including definitions of cancer- and site-specific descriptions (particularly for confusing sites such as abdominal organs), or culturally sensitive suggestions about how to approach family members for information, may help reduce the percentage of ill-defined or inconsistent reports. However, additional research is needed to refine current family history data collection methods.

Conclusion

In conclusion, most family history of cancer reports obtained in this general population survey was coherent, as we have defined it, and surprisingly few relatives had clearly nonmalignant disease misreported as cancer or totally unknown cancer histories. However, the percentage of coherent cancer site reports and known history of any cancers declined for second-degree and deceased relatives and with decreasing educational levels of respondents. Strategies are needed to promote interest in, and increase knowledge of, family history of cancer, particularly in lower socioeconomic populations that are medically underserved and for relatives whose information is harder to ascertain. In population surveys and general epidemiologic studies, the costs versus benefits of including SDR must be carefully considered given the lower interpretive value of their cancer reports. It may be appropriate to exclude collection of SDR information depending on planned applications of the data.

Appendix 1: Examples of Reports about Relatives' Cancers

Consistent with malignancy and provided a specific cancer site: lung cancer; colon cancer; breast cancer; throat cancer of larynx; Paget's disease turned into cancer; in situ breast cancer; cirrhosis of the liver and liver cancer; bladder removed.

Consistent with malignancy but site unspecified: I don't know what type of cancer it was; the cancer was all over; internal cancer that moved so quickly through whole system, liver, stomach, lungs.

Consistent with malignancy but site ill-defined: head and neck cancer; intestinal cancer; either pancreatic or liver cancer; bone and bone marrow cancer; female cancer; cancer in his private parts; tumor near kidney.

Not consistent with malignancy: pre-colon cancer; dysplasia of the cervix; refractory anemia; benign uterine tumors; emphysema; ovarian cyst; benign brain tumor; tuberculosis; dysplasia; hysterectomy, benign.

Indeterminate if cancer or not: lung cancer or emphysema; cancer of the liver or cirrhosis; brain tumor, not sure if cancerous; when she died she had a breast lump, never confirmed as cancer; abnormal PAP smear; skin cancer or growth, not sure if cancer; prostate surgery, I don't know the diagnosis; unknown illness, was in hospital a long time, assume it was cancer; received chemotherapy for cancer, but it turned out not to be cancer; female surgery; throat polyps; bowel polyps.

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.