Family History of Cancers Increases Risk of Renal Cell Carcinoma in a Chinese Population

Figures & data

Table 1 Demographic Characteristics and Baseline Information of the Study Cohort

Variables	Total	RCC		Non-Carcinoma*
		All RCC	ccRCC
Total	484	389	311	95
Gender
Male, n (%)	299	262 (67.4%)	213 (68.5%)	37 (38.9%)
Female, n (%)	189	127 (32.6%)	98 (31.5%)	58 (61.1%)
Age (years), median (IQR)	57 (14–89)	58 (25–84)	59 (30–84)	53 (14–89)
≥50, n (%)	360	301 (77.4%)	246 (79.1%)	59 (62.1%)
<50, n (%)	124	88 (22.6%)	65 (20.9%)	36 (37.9%)
FH of any cancer
Yes, n (%)	119	103 (26.5%)	81 (26.0%)	16 (16.8%)
No, n (%)	365	286 (73.5%)	230 (74.0%)	79 (83.2%)
Grade (Fuhrman)
1	31	31	28	–
2	240	240	212	–
3	65	65	53	–
4	19	19	17	–

Note: *Non-carcinoma: benign pathological diagnosis.

Abbreviations: RCC, renal cell carcinoma; ccRCC, clear cell renal cell carcinoma; FH, family history.

Table 2 Subtype Information of RCC and Benign Pathological Diagnosis

RCC		Benign Pathological Diagnosis
Diagnosis	Cases	Diagnosis	Cases
ccRCC	311	Angiomyolipoma	47
Papillary RCC (pRCC)	40	Complicated cyst	35
Unclassifiable RCC	18	Oncocytoma	10
ccRCC combined with pRCC	6	Lipoma	2
Chromophobe RCC	5	Metanephric adenoma	1
RCC associated with Xp11.2 translocations/TFE3 gene fusions	4
Mucinous tubular and spindle cell renal carcinoma	1
Leiomyosarcoma	1
Sarcomatoid carcinoma	1
Biphasic squamoid alveolar RCC	1
RCC with leiomyomatous stroma	1
Total	389	Total	95

Abbreviations: RCC, renal cell carcinoma; ccRCC, clear cell renal cell carcinoma; pRCC, papillary renal cell carcinoma.

Table 3 Association Between Family History and RCC

Variables	Total	RCC		Non-Carcinoma (n=95)	All RCC vs Non-Carcinoma		ccRCC vs Non-Carcinoma
		All RCC (n=389)	ccRCC (n=311)		OR (95% CI)	P-Value	OR (95% CI)	P-Value
FH of any cancers	119	103 (26.5%)	81 (26.1%)	16 (16.9%)	1.78 (0.99–3.19)	0.062	1.74 (0.96–3.15)	0.074
FH of any cancers in first-degree relatives, n (%)	98	92 (23.7%)	74 (23.8%)	6 (6.3%)	4.60 (1.95–10.85)	5.50×10^−5	4.63 (1.95–11.02)	9.63×10^−5
FH of cancers in different systems
FH of digestive cancers	52	49 (12.6%)	37 (11.9%)	3 (3.2%)	4.42 (1.35–14.51)	0.005	4.14 (1.25–13.75)	6.84×10^−4
FH of pulmonary cancers	29	26 (6.7%)	21 (6.8%)	3 (3.2%)	2.20 (0.65–7.42)	0.24	2.22 (0.65–7.62)	0.32
FH of RCC	7	7 (1.8%)	6 (1.9%)	0 (0.0%)	2.62 (0.14–48.1)	0.59	2.84 (0.15–53.00)	0.59
FH of other cancers	31	21 (5.4%)	17 (5.5%)	10 (10.5%)	0.15 (0.05–0.47)	0.001	0.16 (0.05–0.50)	0.002

Abbreviations: RCC, renal cell carcinoma; ccRCC, clear cell renal cell carcinoma; FH, family history.

Table 4 Multivariate Logistic Regression Analyses Evaluating the Association Between FH and RCC

Variables	RCC vs Non-Carcinoma		ccRCC vs Non-Carcinoma		Low Grade (1–2) vs High Grade (3–4)
	OR (95% CI)	P-Value	OR (95% CI)	P-Value	OR (95% CI)	P-value
Gender	3.34 (2.09–5.32)	<0.001	3.48 (2.14–5.66)	<0.001	2.25 (1.23–4.13)	0.009
Age (≥50 years)	2.08 (1.27–3.40)	0.003	2.38 (1.41–4.00)	0.001	3.72 (1.63–8.50)	0.002
FH of any cancers*	1.85 (1.01–3.37)	0.045	1.90 (1.03–3.53)	0.041	0.73 (0.40–1.35)	0.314
FH of any cancers in first-degree relatives*	4.36 (1.83–10.42)	0.001	4.76 (1.96–11.52)	0.001	0.79 (0.42–1.45)	0.441
FH of digestive cancers*	4.02 (1.21–13.36)	0.023	3.69 (1.10–12.43)	0.035	0.77 (0.35–1.71)	0.522

Note: *Adjusted for gender and age category.

Abbreviations: FH, family history; RCC, renal cell carcinoma.

Table 5 Association Between FH and Age at Onset

Age (Years)	Total	FH		FH in First-Degree Relatives		FH of Digestive Cancers
		Positive	Negative	Positive	Negative	Positive	Negative
RCC patients
≥50, n (%)	301	73 (70.9%)	228 (79.7%)	72 (78.3%)	229 (77.1%)	36 (76.6%)	263 (77.4%)
<50, n (%)	88	30 (29.1%)	58 (20.3%)	20 (21.7%)	68 (22.9%)	11 (23.4%)	77 (22.6%)
P-value		0.075		0.89		0.86
ccRCC patients
≥50, n (%)	246	58 (71.6%)	188 (81.7%)	57 (77.0%)	189 (79.7%)	29 (78.4%)	217 (79.2%)
<50, n (%)	65	23 (28.4%)	42 (18.3%)	17 (23.0%)	48 (20.3%)	8 (21.6%)	57 (20.8%)
P-value		0.058		0.63		1.00

Abbreviations: FH, family history; RCC, renal cell carcinoma, ccRCC, clear cell renal cell carcinoma.

Figure 1 Results of Kaplan–Meier survival analyses: (A) association between FH of all cancer and age at onset of RCC; (B) association between FH in first-degree relatives and age at onset of RCC; (C) association between FH of digestive cancer and age at onset of RCC; (D) association between FH of all cancer and age at onset of ccRCC; (E) association between FH in first-degree relatives and age at onset of ccRCC; (F) association between FH of digestive cancer and age at onset of ccRCC. P-values obtained by log-rank test. HR obtained by log-rank test, with 95% CI in parentheses.

Abbreviations: FH, family history; RCC, renal cell carcinoma; ccRCC, clear cell renal cell carcinoma; HR, hazard ratio; CI, confidence interval.

Figure 2 Graphic presenting significant correlations between FH and RCC. FH of any cancers in first-degree relatives and FH of digestive cancers are considered as risk factors for RCC.

Abbreviations: FH, family history; RCC, renal cell carcinoma; OR, odds ratio; CI, confidence interval.