Information about the family history of cancer in first degree relatives of 1528 cases: (HL (n = 316), MM (n = 342), NHL (n = 513), STS (n = 357)) and 1506 control subjects was obtained. Descriptive characteristics of the families studied are shown in Tables 1 through 4 [See additional file 1 : Table 1; additional file 2 : Table 2; additional file 3 : Table 3; additional file 4 : Table 4]. The age distribution, the mean age and standard deviation, the number of first degree relatives, the mean number of siblings and offspring, and the mean number of first degree family members including parents among controls and within each case group are shown in Table 1 [See additional file 1 : Table 1]. HL cases were much younger compared to MM, NHL, and STS cases. HL families were the smallest with smaller mean number of siblings, sons and daughters compared to families of other case groups and controls. The four categories: small, medium, large and largest categories were used to define the family size (for definition see footnote under Table 2 [See additional file 2 : Table 2]). There were distinctive differences in the family size patterns (chi square = 61.5, df = 12, p <.0001) across the case groups and controls, however the family size patterns were not significantly different between STS cases and controls (Table 2 [See additional file 2 : Table 2], chi square = 1.80, df = 3, p > 0.05). HL families were the smallest. Families of HL, MM and STS were significantly more likely to have had one affected generation than controls, while a higher proportion of NHL families reported two or more affected generations (Table 3 [See additional file 3 : Table 3]). A small minority of families reported affected members in two or more generations. The distribution of affected family members (chi-square = 59.8, df = 8, p <.0001, the categories were zero, one, ≥ 2 affected per family) and the percentage of families with two or more affected individuals are presented in Table 4 [See additional file 4 : Table 4]. The majority of families were cancer free, excluding the index subjects. A minority of families included two or more affected first degree relatives of the index subjects.
Table 5 [See additional file 5 : Table 5] compares distribution of positive history of cancer in (i) at least one parent; (ii) at least one sibling; and (iii) at least one child of each case group with controls stratified by age distribution of the index subject. Patterns of cancer prevalence are similar among the index subjects diagnosed with four types of cancer (HL, MM, NHL, and STS). The index subjects in the age groups > 40, ≤49, and > 49, ≤59 had higher proportion of at least one parent affected with cancer compared to controls. The proportion of at least one sibling affected with cancer increases with age of the index subject. The siblings of older index subjects may be comparatively older compared to the siblings of younger index subjects and it is well known that risk of cancer increases with age. In most of the age groups, index subjects have higher proportion of at least one sibling affected with cancer compared to controls. For the younger age groups (≤40, and > 40, ≤49), there was hardly any child affected with cancer, because children of the index subjects in these age groups may be younger and had very low risk of developing cancer. The proportions of at least one child affected with cancer are small in the older age groups and among all cases and controls.
Families ascertained through HL, MM, NHL, and STS cases were compared to control families in Table 6 [See additional file 6 : Table 6]. Cases of HL [ORadj (95% CI 1.79 (1.33, 2.42)], MM [ORadj (95% CI 1.38 (1.07, 1.78)], NHL [ORadj (95% CI 1.43 (1.15, 1.77)] and STS [1.30 (1.00, 1.68)] were more likely to have at least one first degree relative diagnosed with cancer compared to controls. Although the crude odds ratios (data not shown) for several variables related to history of cancer among families ascertained through HL cases were statistically non-significant, adjustment for age and province of residence produced statistically significant results due to the strength of the associations within certain strata. Index subjects with at least one affected parent with a diagnosis of cancer had increased risk of being diagnosed with HL [1.57 (1.15, 2.14)]. This pattern did not appear in any of the other case/control comparisons. HL [1.94 (1.12, 3.34)], MM [1.71 (1.22, 2.40)] and NHL [1.68 (1.23, 2.31)] cases were significantly more likely to have at least one affected sibling than controls after adjustment for total number of siblings. The excess of siblings was due to more affected sisters among HL families [1.89 (1.05, 3.38)], MM families [1.66 (1.14, 2.40)] and NHL families [1.52 (1.07, 2.17)]. Few children of index subjects (range 0.6% of HL families to 3.7% of MM families) had been diagnosed with cancer.
Among each case/control family group, tumours of the trachea, bronchus, lung (ICD-9 162) and of the female breast (ICD-9 174) were first or second in frequency (data not shown). The female to male ratio for tumours of the trachea, bronchus, and lung was unexpectedly high; 1.45:1 for NHL relatives. There was also one male breast cancer among NHL relatives. Among families of HL cases, lymphoid leukaemia (ICD-9 204) and Hodgkin lymphoma (ICD-9 201) were third and fourth. Among families of MM cases, colon (ICD-9 153) and prostate (ICD-9 185) tumours were third and fourth while stomach (ICD-9 151) and lymphoid leukaemia occupied these ranks among families of NHL cases. Lymphoid leukaemia and liver cancer (ICD-9 155) tied for third place and rectum, sigmoid junction and anus (ICD-9 154) was fourth in frequency among STS families.
In this study, 54.4% of HL cases; 87.7% of MM cases; 79.7% of NHL cases; and 73.7% of STS cases reported to have at least one child compared to 21.4% controls who reported to have at least one child. The HL families reported a higher frequency of birth defects than the control families although there did not appear to be a clustering of specific types (data is not shown). Cleft palate (n = 2) and pyloric stenosis (n = 2) were the only conditions to occur in more than one family while Turner's syndrome, hypospadia and atrophic testis each occurred in one HL family.
Table 7 [See additional file 7 : Table 7] displays certain characteristics of the index subjects stratified by family history of cancer. The variables include pesticide exposure ≥ 10 hours per year as a surrogate for occupational and environmental pesticide exposure, cigarette smoking history (non-smokers, ex-smoker or current smoker) and age at diagnosis. Comparisons of each case group with the controls using mutually exclusive categories combining family history status (positive, negative) with either pesticide exposure ≥ 10 hours/year or lesser exposure indicated that a positive family history (but not pesticide exposure) was important for HL [(2.25 (1.61, 3.15)], that the combination of pesticide exposure and a positive family history of cancer increased risk for MM [1.69 (1.14, 2.51)] and that a positive family history of cancer both with [1.72 (1.21, 2.45)] and without [1.43 (1.12, 1.83)] pesticide exposure increased risk of NHL. A family history of cancer both with [2.34 (1.57, 3.48)] and without [1.68 (1.01, 2.78)] a history of cigarette smoking increased risk of HL. Cigarette smoking [1.46 (1.01, 2.12)] and family history [1.73 (1.07, 2.80)] independently and in combination [1.79 (1.22, 2.63)] increased risk of MM while only the combination of cigarette smoking and a positive family history [1.45 (1.07, 1.96)] influenced risk of NHL. There were no statistically significant results of comparisons of STS cases and controls.
Contrary to the expectation that those with a positive family history of cancer will have experienced genetic and/or environmental factors which might lower the age at diagnosis, HL, MM, and STS cases and the age at recruitment of control subjects with a positive family history were significantly older than those with a negative family history.