Genetic epidemiological analysis reveals a multi-gene additive model for gastric cancer

Abstract

A genetic epidemiologic analysis of gastric cancer in the Chinese Han population was conducted for 64 pedigrees (902 individuals) with gastric cancer and controls obtained from the population after a census was carried out in August 2007. The heritability of gastric cancer was performed using the Falconer method and the complex segregation analysis was performed using the Statistical Analysis for Genetic Epidemiology (S.A.G.E.) SEGREG program. The heritability of gastric cancer in first- and second-degree relatives was 54.75% (95% CI, 48.01–61.49%) and 44.97% (95% CI, 33.12–56.82%), respectively. The estimated segregation ratio of gastric cancer was 0.039 (95% CI, 0.017–0.061). The complex segregation analysis showed that the Mendelian inheritance of additive model provided the best fit to the data (AIC = 170.58, P > 0.05). Therefore, polygenetic or multi-factorial additive inheritance is involved in the genetic predisposition for the development of gastric cancer.

Appendix

The formulae of segregation ratio (P _LM ) estimation:

$$ \begin{gathered} P_{LM} = {{\left( {R - J} \right)} \mathord{\left/ {\vphantom {{\left( {R - J} \right)} {\left( {T - J} \right)}}} \right. \kern-\nulldelimiterspace} {\left( {T - J} \right)}};\,{\kern 1pt} S_{P}^{2} = {{\left( {R - J} \right)\left( {T - R} \right)} \mathord{\left/ {\vphantom {{\left( {R - J} \right)\left( {T - R} \right)} {\left( {T - J} \right)^{3} }}} \right. \kern-\nulldelimiterspace} {\left( {T - J} \right)^{3} }};{\kern 1pt} {\kern 1pt} \,SE_{P} = \left( {S_{p}^{2} } \right)^{1/2} ; \hfill \\ P_{LM} 95\% {\kern 1pt} \,CI: \, P_{LM} \pm 1.96SE_{P} \circ \hfill \\ \end{gathered} $$

Here, P _LM stands for the segregation ratio, R stands for the total number of affected individuals, J stands for the total number of families with only one affected offspring, and T stands for the total number of affected and unaffected offspring.